研究者詳細 - 岸本　泰士郎

論文 - 岸本　泰士郎

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Factors Contributing to the Efficacy of Fecal Microbiota Transplantation for Diarrhea-Dominant Functional Bowel Disorders.

Yamane T, Masaoka T, Ishii C, Masuoka H, Suda W, Kurokawa S, Kishimoto T, Mikami Y, Fukuda S, Kanai T

Digestion 1 - 11 2025年04月

ISSN 0012-2823

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Collaborative Outcomes Study on Health and Functioning During Infection Times (COH-FIT): Global and Risk-Group Stratified Course of Well-Being and Mental Health During the COVID-19 Pandemic in Adolescents

Solmi M., Thompson T., Cortese S., Estradé A., Agorastos A., Radua J., Dragioti E., Vancampfort D., Thygesen L.C., Aschauer H., Schlögelhofer M., Aschauer E., Schneeberger A.A., Huber C.G., Hasler G., Conus P., Do Cuénod K.Q., von Känel R., Arrondo G., Fusar-Poli P., Gorwood P., Llorca P.M., Krebs M.O., Scanferla E., Kishimoto T., Rabbani G., Skonieczna-Żydecka K., Brambilla P., Favaro A., Takamiya A., Zoccante L., Colizzi M., Bourgin J., Kamiński K., Moghadasin M., Seedat S., Matthews E., Wells J., Vassilopoulou E., Gadelha A., Su K.P., Kwon J.S., Kim M., Lee T.Y., Papsuev O., Manková D., Boscutti A., Gerunda C., Saccon D., Righi E., Monaco F., Croatto G., Cereda G., Demurtas J., Brondino N., Veronese N., Enrico P., Politi P., Ciappolino V., Pfennig A., Bechdolf A., Meyer-Lindenberg A., Kahl K.G., Domschke K., Bauer M., Koutsouleris N., Winter S., Borgwardt S., Bitter I., Balazs J., Czobor P., Unoka Z., Mavridis D., Tsamakis K., Bozikas V.P., Tunvirachaisakul C., Maes M., Rungnirundorn T., Supasitthumrong T., Haque A., Brunoni A.R., Costardi C.G., Schuch F.B., Polanczyk G., Luiz J.M., Fonseca L., Aparicio L.V., Valvassori S.S., Nordentoft M., Vendsborg P., Hoffmann S.H., Sehli J., Sartorius N., Heuss S., Guinart D., Hamilton J., Kane J., Rubio J., Sand M., Koyanagi A.

Journal of the American Academy of Child and Adolescent Psychiatry 64 （ 4 ） 499 - 519 2025年04月

ISSN 08908567

Objective: To identify the COVID-19 pandemic impact on well-being/mental health, coping strategies, and risk factors in adolescents worldwide. Method: This study was based on an anonymous online multi-national/multi-language survey in the general population (representative/weighted non-representative samples, 14-17 years of age), measuring change in well-being (World Health Organization–Five Well-Being Index [WHO-5]/range = 0-100) and psychopathology (validated composite P-score/range = 0-100), WHO-5 <50 and <29, pre- vs during COVID-19 pandemic (April 26, 2020-June 26, 2022). Coping strategies and 9 a priori– defined individual/cumulative risk factors were measured. A χ2, penalized cubic splines, linear regression, and correlation analyses were conducted. Results: Analyzing 8,115 of 8,762 initiated surveys (representative = 75.1%), the pre-pandemic WHO-5 and P-score remained stable during the study (excluding relevant recall bias/drift), but worsened during the pandemic by 5.55 ± 17.13 (SD) and 6.74 ± 16.06 points, respectively (effect size d = 0.27 and d = 0.28). The proportion of adolescents with WHO-5 scores suggesting depression screening (<50) and major depression (<29) increased from 9% to 17% and 2% to 6%. WHO-5 worsened (descending magnitude, with cumulative effect) in adolescents with a mental or physical disorder, female gender, and with school closure. Results were similar for the P-score, with the exception of school closure (not significant) and living in a low-income country, as well as not living in a large city (significant). Changes were significantly but minimally related to COVID-19 deaths/restrictions, returning to near–pre-pandemic values after >2 years. The 3 most subjectively effective coping strategies were Internet use, exercise/walking, and social contacts. Conclusion: Overall, well-being/mental health worsened (small effect sizes) during the early stages of the COVID-19 pandemic, especially in vulnerable subpopulations. Identified at-risk groups, association with pandemic-related measures, and coping strategies can inform individual behaviors and global public health strategies. Plain language summary: The impact of COVID-19 and related restrictions on the mental health of children and adolescents remains unclear. This study conducted an anonymous online survey with over 8,100 adolescents aged 14 to 17 years worldwide. Results showed a significant decline in wellbeing, with depression rates increasing from 9% to 17% returning to near- pre-pandemic values after about 2 years. Adolescents with preexisting mental health conditions, female youth, and those affected by school closures were particularly vulnerable. Effective coping strategies included internet use, exercise, and social contacts, highlighting areas for public health focus to support youth during pandemics. Study preregistration information: Physical and mental health impact of COVID-19 on children, adolescents, and their families: The Collaborative Outcomes study on Health and Functioning during Infection Times - Children and Adolescents (COH-FIT-C&A); https://doi.org/10.1016/j.jad.2021.09.090 Diversity & Inclusion Statement: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. We actively worked to promote sex and gender balance in our author group. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science.

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Electrodermal activity and skin temperature characteristics related to stress and depression: A 4-week observational study of office workers

Ishikawa Y., Sugio T., Shiga K., Izumi K., Minato K., Kitazawa M., Hanashiro S., Takemura R., Uchida H., Kishimoto T.

Journal of Affective Disorders Reports 20 2025年04月

Background: Mental health problems, particularly depression, significantly impact the working-age population and incur substantial socioeconomic costs. Electrodermal activity (EDA) and skin temperature, measurable through wearable devices, have emerged as potential biomarkers of depression. However, there is a lack of long-term observational studies in real-world settings. Methods: This 4-week observational study analyzed data from 147 office workers across 11 Japanese companies. Participants wore wearable devices during working hours for four weeks to collect EDA and skin temperature data. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9), and stress was assessed using the 10-item version of the Perceived Stress Scale (PSS-10). The associations between electrodermal activity, skin temperature, and depressive/stress states were analyzed using the Mann–Whitney U test and logistic regression analysis. Results: Participants with PHQ-9 scores ≥5 showed higher median skin conductance and median tonic signal, although these differences lost statistical significance after Bonferroni correction. Logistic regression analysis revealed a negative correlation between age and both PHQ-9 and PSS-10 scores (OR=0.525, 0.646). The mean and standard deviation of skin temperature showed a positive association with depressive symptoms (OR=1.687, 1.733), while normalized EDASymp showed a negative association (OR=0.564). Conclusions: This study suggests that EDA and skin temperature, measured by wearable devices, may be associated with depressive symptoms among office workers. These physiological indicators could be utilized for mental health monitoring and early intervention in the workplace. Further validation with larger samples, and long-term follow-up studies, are warranted.

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特集精神疾患診療へのデジタルツールの活用精神疾患患者に対する非薬物療法におけるデジタルツールの開発の流れと展望

古川渉太, 木下翔太郎, 岸本泰士郎

精神医学（株式会社医学書院） 67 （ 1 ） 5 - 11 2025年01月

ISSN 04881281

Collaborative outcomes study on health and functioning during infection times (COH-FIT): Insights on modifiable and non-modifiable risk and protective factors for wellbeing and mental health during the COVID-19 pandemic from multivariable and network analyses

Solmi M., Thompson T., Cortese S., Estradé A., Agorastos A., Radua J., Dragioti E., Vancampfort D., Thygesen L.C., Aschauer H., Schlögelhofer M., Aschauer E., Schneeberger A., Huber C.G., Hasler G., Conus P., Cuénod K.Q.D., von Känel R., Arrondo G., Fusar-Poli P., Gorwood P., Llorca P.M., Krebs M.O., Scanferla E., Kishimoto T., Rabbani G., Skonieczna-Żydecka K., Brambilla P., Favaro A., Takamiya A., Zoccante L., Colizzi M., Bourgin J., Kamiński K., Moghadasin M., Seedat S., Matthews E., Wells J., Vassilopoulou E., Gadelha A., Su K.P., Kwon J.S., Kim M., Lee T.Y., Papsuev O., Manková D., Boscutti A., Gerunda C., Saccon D., Righi E., Monaco F., Croatto G., Cereda G., Demurtas J., Brondino N., Veronese N., Enrico P., Politi P., Ciappolino V., Pfennig A., Bechdolf A., Meyer-Lindenberg A., Kahl K.G., Domschke K., Bauer M., Koutsouleris N., Winter S., Borgwardt S., Bitter I., Balazs J., Czobor P., Unoka Z., Mavridis D., Tsamakis K., Bozikas V.P., Tunvirachaisakul C., Maes M., Rungnirundorn T., Supasitthumrong T., Haque A., Brunoni A.R., Costardi C.G., Schuch F.B., Polanczyk G., Luiz J.M., Fonseca L., Aparicio L.V., Valvassori S.S., Nordentoft M., Vendsborg P., Hoffmann S.H., Sehli J., Sartorius N., Heuss S., Guinart D., Hamilton J., Kane J., Rubio J., Sand M., Koyanagi A.

European Neuropsychopharmacology 90 1 - 15 2025年01月

ISSN 0924977X

There is no multi-country/multi-language study testing a-priori multivariable associations between non-modifiable/modifiable factors and validated wellbeing/multidimensional mental health outcomes before/during the COVID-19 pandemic. Moreover, studies during COVID-19 pandemic generally do not report on representative/weighted non-probability samples. The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is a multi-country/multi-language survey conducting multivariable/LASSO-regularized regression models and network analyses to identify modifiable/non-modifiable factors associated with wellbeing (WHO-5)/composite psychopathology (P-score) change. It enrolled general population-representative/weighted-non-probability samples (26/04/2020-19/06/2022). Participants included 121,066 adults (age=42±15.9 years, females=64 %, representative sample=29 %) WHO-5/P-score worsened (SMD=0.53/SMD=0.74), especially initially during the pandemic. We identified 15 modifiable/nine non-modifiable risk and 13 modifiable/three non-modifiable protective factors for WHO-5, 16 modifiable/11 non-modifiable risk and 10 modifiable/six non-modifiable protective factors for P-score. The 12 shared risk/protective factors with highest centrality (network-analysis) were, for non-modifiable factors, country income, ethnicity, age, gender, education, mental disorder history, COVID-19-related restrictions, urbanicity, physical disorder history, household room numbers and green space, and socioeconomic status. For modifiable factors, we identified medications, learning, internet, pet-ownership, working and religion as coping strategies, plus pre-pandemic levels of stress, fear, TV, social media or reading time, and COVID-19 information. In multivariable models, for WHO-5, additional non-modifiable factors with |B|>1 were income loss, COVID-19 deaths. For modifiable factors we identified pre-pandemic levels of social functioning, hobbies, frustration and loneliness, and social interactions as coping strategy. For P-scores, additional non-modifiable/modifiable factors were income loss, pre-pandemic infection fear, and social interactions as coping strategy. COH-FIT identified vulnerable sub-populations and actionable individual/environmental factors to protect well-being/mental health during crisis times. Results inform public health policies, and clinical practice.

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Dementia and MCI Detection Based on Comprehensive Facial Expression Analysis From Videos During Conversation

Okunishi T., Zheng C., Bouazizi M., Ohtsuki T., Kitazawa M., Horigome T., Kishimoto T.

IEEE Journal of Biomedical and Health Informatics 29 （ 5 ） 3537 - 3548 2025年

ISSN 21682194

The development of a cost-effective digital biomarker for detecting dementia is highly needed. While numerous studies have explored dementia detection through speech and natural language analysis, only a few studies have focused on dementia detection using face video recordings, and more in-depth research is needed. In this paper, we propose a method for detecting dementia and mild cognitive impairment (MCI), a pre-dementia stage, by utilizing four types of facial expression features extracted from recorded videos of participants. These features include Action Units, emotion categories, Valence-Arousal, and face embeddings. From the above features obtained from each video frame, various statistical information was extracted and used as features, and predictions were performed using a decision tree-based model. Our method was evaluated using face video recordings during conversations. The method achieved an area under the receiver operating characteristic curve (AUC) of 0.933 for dementia detection and 0.889 for MCI detection. Statistical analysis of facial expression features revealed that participants with dementia had fewer positive emotions, more negative emotions, and lower valence and arousal than healthy participants. These results indicate that the proposed method could serve as an explainable screening tool for the early detection of dementia and MCI.

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Enhancing Dementia Detection: Augmenting the Face Mesh

Zheng C., Bouazizi M., Ohtsuki T., Kitazawa M., Horigome T., Kishimoto T.

Proceedings International Symposium on Biomedical Imaging 2025年

ISSN 19457928

Alzheimer's disease (AD) stands as a prevalent form of dementia, primarily impacting the elderly, and presently lacking any known cure. Early screening and intervention have demonstrated efficacy for both current and prospective treatments. With the global population aging, early detection of AD has become imperative. Language-based approaches for dementia detection have received considerable attention in research due to dementia's nature of hurting cognitive and language functions. Facial features, on the other hand, have been comparatively neglected despite their potential in identifying AD, due to a lack of usable dataset. AD patients show different patterns while displaying facial expressions because of Apathy, a phenomenon common in AD patients. This makes facial features non-negligible in dementia detection. The face mesh, comprising 478 landmarks, serves as a rich and informative facial representation. This study concentrates on leveraging face mesh data for AD detection. We explored data augmentation techniques to address the challenges of over-fitting, particularly impactful in training neural networks on a small dataset. Deep learning methods, including transformer, Convolutional Neural Networks (CNN), and Long Short-Term Memory (LSTM) networks, were employed to classify dementia patients and healthy subjects. By augmenting the dataset by rotation, shift, and scaling, we improved the performance of the deep learning methods. The combined use of 1D CNN networks and data augmentation method reported the highest accuracy of 76%. These results confirmed the effectiveness of our data augmentation methods. They also underscore the potential of face-related features in enhancing early detection approaches for AD.

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Computer-Assisted Noise Pareidolia Tests Through Patient Emulation

Zhu Z., Kastner M.A., Nakajima K., Furukawa S., Kitazawa M., Kishimoto T., Satoh S.

IEEE Access 13 64271 - 64289 2025年

ISSN 2169-3536

Pareidolia is a psychiatric phenomenon similar to visual illusions or hallucinations, serving as a distinguishing feature of psychiatric disorders. The so-called noise pareidolia test is a typical diagnosis method for pareidolia. In the test, ambiguous noise-like images are shown to patients, to see if patients misunderstand them as faces. However, the existing testing method is very time-consuming for both patients and experts. Furthermore, it has low accuracy in distinguishing some psychiatric disorders with similar characteristics. This research presents a machine learning-based framework to assist in assessing the pareidolia phenomenon. This is a challenging task because analyzing psychiatric disorders primarily involves observing behavioral changes. This is in contrast to other medical imaging tasks which rely on physically visible changes. Our framework emulates the behavior of patients in noise pareidolia tests. To achieve this, we fine-tune face detection models on patient data to misunderstand ambiguous patterns in the same way a patient would do. Then, we can compare new patients to the behavior of existing patients to assess the pareidolia phenomenon, through two classification approaches: a distance function-based approach and a multilayer perceptron-based approach. The proposed framework is evaluated on the data from 48 real patients. The result shows a performance superior to baseline methods in distinguishing pareidolia from other similar visual illusions. Moreover, our framework introduces two sampling methods to reduce the number of images shown to the patient while reaching a comparable high accuracy, improving the efficiency and making the framework feasible for a clinical test.

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Increase in the number of female doctors and the challenges that Japan's medical system must face

Kinoshita, S; Kishimoto, T

Global Health & Medicine （国立研究開発法人国立国際医療研究センター） 6 （ 6 ） 433 - 435 2024年12月

ISSN 24349186

Japan has seen an increase in female physicians recently, yet it still lags behind other Organization for Economic Cooperation and Development (OECD) countries. A major barrier has been the historical discrimination against women in medical school admissions. In recent years, female enrolment in medical schools has risen, surpassing 40% in 2024, reflecting a broader societal shift. However, structural problems persist in the Japanese healthcare system. Although the number of doctors per capita is lower in Japan than in other countries, the number of patients is higher than in other countries, leading to overwork for doctors. As a result, only about one-third of female doctors in Japan are able to return to work after interrupting their careers to give birth or raise children. The maldistribution of physicians, both regionally and by specialty, exacerbates this issue. To sustain the rising number of female physicians, Japan must reform its medical system.

Amyloid-β prediction machine learning model using source-based morphometry across neurocognitive disorders

Momota Y., Bun S., Hirano J., Kamiya K., Ueda R., Iwabuchi Y., Takahata K., Yamamoto Y., Tezuka T., Kubota M., Seki M., Shikimoto R., Mimura Y., Kishimoto T., Tabuchi H., Jinzaki M., Ito D., Mimura M.

Scientific Reports 14 （ 1 ） 7633 2024年12月

ISSN 2045-2322

Previous studies have developed and explored magnetic resonance imaging (MRI)-based machine learning models for predicting Alzheimer’s disease (AD). However, limited research has focused on models incorporating diverse patient populations. This study aimed to build a clinically useful prediction model for amyloid-beta (Aβ) deposition using source-based morphometry, using a data-driven algorithm based on independent component analyses. Additionally, we assessed how the predictive accuracies varied with the feature combinations. Data from 118 participants clinically diagnosed with various conditions such as AD, mild cognitive impairment, frontotemporal lobar degeneration, corticobasal syndrome, progressive supranuclear palsy, and psychiatric disorders, as well as healthy controls were used for the development of the model. We used structural MR images, cognitive test results, and apolipoprotein E status for feature selection. Three-dimensional T1-weighted images were preprocessed into voxel-based gray matter images and then subjected to source-based morphometry. We used a support vector machine as a classifier. We applied SHapley Additive exPlanations, a game-theoretical approach, to ensure model accountability. The final model that was based on MR-images, cognitive test results, and apolipoprotein E status yielded 89.8% accuracy and a receiver operating characteristic curve of 0.888. The model based on MR-images alone showed 84.7% accuracy. Aβ-positivity was correctly detected in non-AD patients. One of the seven independent components derived from source-based morphometry was considered to represent an AD-related gray matter volume pattern and showed the strongest impact on the model output. Aβ-positivity across neurological and psychiatric disorders was predicted with moderate-to-high accuracy and was associated with a probable AD-related gray matter volume pattern. An MRI-based data-driven machine learning approach can be beneficial as a diagnostic aid.

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Global and risk-group stratified well-being and mental health during the COVID-19 pandemic in adults: Results from the international COH-FIT Study

Solmi M., Thompson T., Estradé A., Agorastos A., Radua J., Cortese S., Dragioti E., Vancampfort D., Thygesen L.C., Aschauer H., Schlögelhofer M., Aschauer E., Schneeberger A., Huber C.G., Hasler G., Conus P., Cuénod K.Q.D., von Känel R., Arrondo G., Fusar-Poli P., Gorwood P., Llorca P.M., Krebs M.O., Scanferla E., Kishimoto T., Rabbani G., Skonieczna-Żydecka K., Brambilla P., Favaro A., Takamiya A., Zoccante L., Colizzi M., Bourgin J., Kamiński K., Moghadasin M., Seedat S., Matthews E., Wells J., Vassilopoulou E., Gadelha A., Su K.P., Kwon J.S., Kim M., Lee T.Y., Papsuev O., Manková D., Boscutti A., Gerunda C., Saccon D., Righi E., Monaco F., Croatto G., Cereda G., Demurtas J., Brondino N., Veronese N., Enrico P., Politi P., Ciappolino V., Pfennig A., Bechdolf A., Meyer-Lindenberg A., Kahl K.G., Domschke K., Bauer M., Koutsouleris N., Winter S., Borgwardt S., Bitter I., Balazs J., Czobor P., Unoka Z., Mavridis D., Tsamakis K., Bozikas V.P., Tunvirachaisakul C., Maes M., Rungnirundorn T., Supasitthumrong T., Haque A., Brunoni A.R., Costardi C.G., Schuch F.B., Polanczyk G., Luiz J.M., Fonseca L., Aparicio L.V., Valvassori S.S., Nordentoft M., Vendsborg P., Hoffmann S.H., Sehli J., Sartorius N., Heuss S., Guinart D., Hamilton J., Kane J., Rubio J., Sand M., Koyanagi A.

Psychiatry Research 342 115972 2024年12月

ISSN 01651781

International studies measuring wellbeing/multidimensional mental health before/ during the COVID-19 pandemic, including representative samples for >2 years, identifying risk groups and coping strategies are lacking. COH-FIT is an online, international, anonymous survey measuring changes in well-being (WHO-5) and a composite psychopathology P-score, and their associations with COVID-19 deaths/restrictions, 12 a-priori defined risk individual/cumulative factors, and coping strategies during COVID-19 pandemic (26/04/2020-26/06/2022) in 30 languages (representative, weighted non-representative, adults). T-test, χ2, penalized cubic splines, linear regression, correlation analyses were conducted. Analyzing 121,066/142,364 initiated surveys, WHO-5/P-score worsened intra-pandemic by 11.1±21.1/13.2±17.9 points (effect size d=0.50/0.60) (comparable results in representative/weighted non-probability samples). Persons with WHO-5 scores indicative of depression screening (<50, 13% to 32%) and major depression (<29, 3% to 12%) significantly increased. WHO-5 worsened from those with mental disorders, female sex, COVID-19-related loss, low-income country location, physical disorders, healthcare worker occupations, large city location, COVID-19 infection, unemployment, first-generation immigration, to age=18-29 with a cumulative effect. Similar findings emerged for P-score. Changes were significantly but minimally related to COVID-19 deaths, returning to near-pre-pandemic values after >2 years. The most subjectively effective coping strategies were exercise and walking, internet use, social contacts. Identified risk groups, coping strategies and outcome trajectories can inform global public health strategies.

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Updating the Japanese Healthcare System to Meet the Needs of an Aging Society

Kinoshita, S; Kishimoto, T

JMA JOURNAL 2024年10月

ISSN 2433-328X

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A comparative study on dietary diversity and gut microbial diversity in children with autism spectrum disorder, attention-deficit hyperactivity disorder, their neurotypical siblings, and non-related neurotypical volunteers: a cross-sectional study

Kurokawa S., Nomura K., Sanada K., Miyaho K., Ishii C., Fukuda S., Iwamoto C., Naraoka M., Yoneda S., Imafuku M., Matsuzaki J., Saito Y., Mimura M., Kishimoto T.

Journal of Child Psychology and Psychiatry and Allied Disciplines 65 （ 9 ） 1184 - 1195 2024年09月

ISSN 00219630

Background: Previous research has shown a significant link between gut microbiota in children with autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). However, much remains unknown because of the heterogeneity of disorders and the potential confounders such as dietary patterns and control group variations. Methods: Children aged 6–12 years who had been clinically diagnosed with ASD and/or ADHD, their unaffected neurotypical siblings, and non-related neurotypical volunteers were recruited cross-sectionally. The ASD diagnosis was confirmed using the Autism Diagnostic Observation Schedule-2 (ADOS-2) in all patients, including those with ADHD. Standardized DNA extraction and sequencing methods were used to compare gut microbial alpha-diversity among the groups. Dietary diversity was calculated from a standardized dietary questionnaire form. We compared the difference in gut microbiome between patients with ASD and/or ADHD with neurotypical siblings and non-related neurotypical controls. Results: Ninety-eight subjects were included in the study (18 with ASD, 19 with ADHD, 20 with both ASD and ADHD, 13 neurotypical siblings, and 28 non-related neurotypical controls). The alpha-diversity indices, such as Chao 1 and Shannon index, showed a significant difference between the groups in a Linear mixed-effect model (F(4, 93) = 4.539, p =.02), (F(4, 93) = 3.185, p =.017), respectively. In a post-hoc pairwise comparison, patients with ASD had lower alpha-diversity compared with non-related controls after Bonferroni correction. Dietary diversity shown in Shannon index did not differ among the groups (F(4, 84) = 1.494, p =.211). Conclusions: Our study indicates disorder-specific microbiome differences in patients with ASD. In future research on gut microbiota in neurodevelopmental disorders, it is necessary to consider the impact of ASD and ADHD co-occurrence, and strictly control for background information such as diet, to elucidate the gut–microbiota interaction in ASD and ADHD for exploring the potential of therapeutic interventions.

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Ageing population in Japan: immediate shake-up in healthcare required

Kinoshita, S; Kishimoto, T

QJM-AN INTERNATIONAL JOURNAL OF MEDICINE 2024年05月

ISSN 1460-2725

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特集よくわかる!　精神疾患対応これ1冊-内科医と精神科医の連携のために第8部　知っておきたい最近の精神疾患関連トピックス 14　オンライン精神科診療

木下翔太郎, 岸本泰士郎

診断と治療（診断と治療社） 112 （ 13 ） 370 - 374 2024年03月

ISSN 0370999X

特集うつ病のバイオマーカー開発の試み心拍変動・行動指標を用いたデジタルフェノタイピングに向けて

石川祐希, 堀込俊郎, 岸本泰士郎

精神医学（株式会社医学書院） 66 （ 2 ） 187 - 191 2024年02月

ISSN 04881281

Intestinal metabolites predict treatment resistance of patients with depression and anxiety.

Matsuzaki J, Kurokawa S, Iwamoto C, Miyaho K, Takamiya A, Ishii C, Hirayama A, Sanada K, Fukuda S, Mimura M, Kishimoto T, Saito Y

Gut pathogens 16 （ 1 ） 8 2024年02月

ISSN 1757-4749

Background: The impact of the gut microbiota on neuropsychiatric disorders has gained much attention in recent years; however, comprehensive data on the relationship between the gut microbiome and its metabolites and resistance to treatment for depression and anxiety is lacking. Here, we investigated intestinal metabolites in patients with depression and anxiety disorders, and their possible roles in treatment resistance. Results: We analyzed fecal metabolites and microbiomes in 34 participants with depression and anxiety disorders. Fecal samples were obtained three times for each participant during the treatment. Propensity score matching led us to analyze data from nine treatment responders and nine non-responders, and the results were validated in the residual sample sets. Using elastic net regression analysis, we identified several metabolites, including N-ε-acetyllysine; baseline levels of the former were low in responders (AUC = 0.86; 95% confidence interval, 0.69–1). In addition, fecal levels of N-ε-acetyllysine were negatively associated with the abundance of Odoribacter. N-ε-acetyllysine levels increased as symptoms improved with treatment. Conclusion: Fecal N-ε-acetyllysine levels before treatment may be a predictive biomarker of treatment-refractory depression and anxiety. Odoribacter may play a role in the homeostasis of intestinal L-lysine levels. More attention should be paid to the importance of L-lysine metabolism in those with depression and anxiety.

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Feasibility of remote interviews in assessing disease severity in patients with major depressive disorder: A pilot study

Sumiyoshi, T; Morio, Y; Kawashima, T; Tachimori, H; Hongo, S; Kishimoto, T; Watanabe, K; Otsubo, T; Oi, H; Nakagome, K; Ishigooka, J

NEUROPSYCHOPHARMACOLOGY REPORTS 44 （ 1 ） 149 - 157 2024年01月

Aim: Interview quality is an important factor in the success of clinical trials for major depressive disorder (MDD). There is a substantial need to establish a reliable, remote clinical assessment interview system that can replace traditional in-person interviews. Methods: We conducted a multicenter, randomized, unblinded, prospective, cross-sectional study to assess the reliability of remote interviews in patients with MDD (UMIN000041839). Eligible patients with MDD underwent remote and in-person sessions of the Montgomery-Åsberg Depression Rating Scale (MADRS) assessment performed by different raters within 28 days of providing consent. Patients were randomized to a group first assessed using in-person interviews and secondarily using remote interviews (in-person-first group) or a group first assessed by remote interviews and secondarily using in-person interviews (remote-first group). Nineteen trained people (15 clinical psychologists, 3 nurses, and 1 clinical laboratory technologist) performed interviews. Results: Of 59 patients (in-person-first group, n = 32; remote-first group, n = 27) who completed both remote and in-person interviews, 51% (n = 30) were women; the mean age was 41.6 years (range, 21–64 years). There was a strong association between remote and in-person MADRS scores (r = 0.891, kappa = 0.901). An overall intraclass correlation coefficient (ICC) of 0.886 (95% confidence interval, 0.877–0.952) indicated good consistency between MADRS scores in remote and in-person interviews. The ICC decreased as the severity of depression increased. Conclusion: Our results suggest remote interviews are a feasible alternative option to in-person interviews in assessing symptom severity in MDD patients and could promote clinical trials in Japan.

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Assessment of Stress and Well-Being of Japanese Employees Using Wearable Devices for Sleep Monitoring Combined With Ecological Momentary Assessment: Pilot Observational Study

Kinoshita S., Hanashiro S., Tsutsumi S., Shiga K., Kitazawa M., Wada Y., Inaishi J., Kashiwagi K., Fukami T., Mashimo Y., Minato K., Kishimoto T.

JMIR Formative Research 8 e49396 2024年

Background: Poor sleep quality can elevate stress levels and diminish overall well-being. Japanese individuals often experience sleep deprivation, and workers have high levels of stress. Nevertheless, research examining the connection between objective sleep assessments and stress levels, as well as overall well-being, among Japanese workers is lacking. Objective: This study aims to investigate the correlation between physiological data, including sleep duration and heart rate variability (HRV), objectively measured through wearable devices, and 3 states (sleepiness, mood, and energy) assessed through ecological momentary assessment (EMA) and use of rating scales for stress and well-being. Methods: A total of 40 office workers (female, 20/40, 50%; mean age 40.4 years, SD 11.8 years) participated in the study. Participants were asked to wear a wearable wristband device for 8 consecutive weeks. EMA regarding sleepiness, mood, and energy levels was conducted via email messages sent by participants 4 times daily, with each session spaced 3 hours apart. This assessment occurred on 8 designated days within the 8-week timeframe. Participants’ stress levels and perception of well-being were assessed using respective self-rating questionnaires. Subsequently, participants were categorized into quartiles based on their stress and well-being scores, and the sleep patterns and HRV indices recorded by the Fitbit Inspire 2 were compared among these groups. The Mann-Whitney U test was used to assess differences between the quartiles, with adjustments made for multiple comparisons using the Bonferroni correction. Furthermore, EMA results and the sleep and HRV indices were subjected to multilevel analysis for a comprehensive evaluation. Results: The EMA achieved a total response rate of 87.3%, while the Fitbit Inspire 2 wear rate reached 88.0%. When participants were grouped based on quartiles of well-being and stress-related scores, significant differences emerged. Specifically, individuals in the lowest stress quartile or highest subjective satisfaction quartile retired to bed earlier (P<.001 and P=.01, respectively), whereas those in the highest stress quartile exhibited greater variation in the midpoint of sleep (P<.001). A multilevel analysis unveiled notable relationships: intraindividual variability analysis indicated that higher energy levels were associated with lower deviation of heart rate during sleep on the preceding day (β=–.12, P<.001), and decreased sleepiness was observed on days following longer sleep durations (β=–.10, P<.001). Furthermore, interindividual variability analysis revealed that individuals with earlier midpoints of sleep tended to exhibit higher energy levels (β=–.26, P=.04). Conclusions: Increased sleep variabilities, characterized by unstable bedtime or midpoint of sleep, were correlated with elevated stress levels and diminished well-being. Conversely, improved sleep indices (eg, lower heart rate during sleep and earlier average bedtime) were associated with heightened daytime energy levels. Further research with a larger sample size using these methodologies, particularly focusing on specific phenomena such as social jet lag, has the potential to yield valuable insights.

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精神疾患会話コーパスを用いた笑い自動検出器構築と疾患分類

香月祥, 中村啓伸, 岸本泰士郎, 狩野芳伸

人工知能学会全国大会論文集（一般社団法人人工知能学会） JSAI2024 （ 0 ） 3Xin209 - 3Xin209 2024年

我々が構築してきた UNDERPIN大規模精神疾患会話コーパスは被験者の各種診断結果とその会話録音からなり、すべての会話録音を人手で文字起こししてきた。さらに、その一部に人手で詳細な音声的・言語学的アノテーションを付与してきた。しかし、将来的な自動診断支援という実用も考えると、アノテーションの自動的な付与が望ましい。また、これまでの我々の研究では、音声特徴量として笑いの統計が、疾患にかかわらず推測の重要な手掛かりであることが示唆されてきたが、笑いに関してもこの人手のアノテーションに依存している。本研究ではUNDERPINコーパスに対して笑いのアノテーション付与を行い、これにより音声認識システムWhisperのファインチューニングを行って笑いの自動検出システムを構築した。笑いの検出性能は90%を超え実用レベルの高い性能を達成した。構築した笑い自動検出システムを用いて、UNDERPINコーパスのし対話テキストデータにアノテーション付与を行い疾患分類実験を行った。結果、人手のアノーションを利用した場合と同等程度の性能となり、応用においても実用レベルの性能を示した。

Reliability of Telepsychiatry Assessments Using the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV for Children With Neurodevelopmental Disorders and Their Caregivers: Randomized Feasibility Study

Kurokawa S., Nomura K., Hosogane N., Nagasawa T., Kawade Y., Matsumoto Y., Morinaga S., Kaise Y., Higuchi A., Goto A., Inada N., Kodaira M., Kishimoto T.

Journal of Medical Internet Research 26 （ 1 ） e51749 2024年

ISSN 1438-8871

Background: Given the global shortage of child psychiatrists and barriers to specialized care, remote assessment is a promising alternative for diagnosing and managing attention-deficit/hyperactivity disorder (ADHD). However, only a few studies have validated the accuracy and acceptability of these remote methods. Objective: This study aimed to test the agreement between remote and face-to-face assessments. Methods: Patients aged between 6 and 17 years with confirmed Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnoses of ADHD or autism spectrum disorder (ASD) were recruited from multiple institutions. In a randomized order, participants underwent 2 evaluations, face-to-face and remotely, with distinct evaluators administering the ADHD Rating Scale-IV (ADHD-RS-IV). Intraclass correlation coefficient (ICC) was used to assess the reliability of face-to-face and remote assessments. Results: The participants included 74 Japanese children aged between 6 and 16 years who were primarily diagnosed with ADHD (43/74, 58%) or ASD (31/74, 42%). A total of 22 (30%) children were diagnosed with both conditions. The ADHD-RS-IV ICCs between face-to-face and remote assessments showed “substantial” agreement in the total ADHD-RS-IV score (ICC=0.769, 95% CI 0.654-0.849; P<.001) according to the Landis and Koch criteria. The ICC in patients with ADHD showed “almost perfect” agreement (ICC=0.816, 95% CI 0.683-0.897; P<.001), whereas in patients with ASD, it showed “substantial” agreement (ICC=0.674, 95% CI 0.420-0.831; P<.001), indicating the high reliability of both methods across both conditions. Conclusions: Our study validated the feasibility and reliability of remote ADHD testing, which has potential benefits such as reduced hospital visits and time-saving effects. Our results highlight the potential of telemedicine in resource-limited areas, clinical trials, and treatment evaluations, necessitating further studies to explore its broader application.

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Home-Based Cognitive Intervention for Healthy Older Adults Through Asking Robots Questions: Randomized Controlled Trial

Tokunaga S., Sekiguchi T., Miura K.W., Sugimoto H., Abe M.S., Tamura K., Kishimoto T., Kudo T., Otake-Matsuura M.

JMIR Aging 7 e47229 2024年

Background: Asking questions is common in conversations, and while asking questions, we need to listen carefully to what others say and consider the perspective our questions adopt. However, difficulties persist in verifying the effect of asking questions on older adults’ cognitive function due to the lack of a standardized system for conducting experiments at participants’ homes. Objective: This study examined the intervention effect of cognitive training moderated by robots on healthy older adults. A focus on the feasibility of the intervention at participants’ homes was also maintained. Feasibility was evaluated by considering both the dropout rate during the intervention and the number of questions posed to each participant during the experiment. Methods: We conducted a randomized controlled trial with 81 adults older than 65 years. Participants were recruited through postal invitations and then randomized into 2 groups. The intervention group (n=40) received sessions where participants listened to photo-integrated stories and posed questions to the robots. The control group (n=41) received sessions where participants listened to photo-integrated stories and only thanked the robots for confirming participation. The participants participated in 12 dialogue sessions for 2-3 weeks. Scores of global cognitive functioning tests, recall tests, and verbal fluency tasks measured before and after the intervention were compared between the 2 groups. Results: There was no significant intervention effect on the Telephone Interview for Cognitive Status-Japanese scores, recall tests, and verbal fluency tasks. Additionally, our study successfully concluded with no participant dropouts at follow-up, confirming the feasibility of our approach. Conclusions: There was no statistically significant evidence indicating intervention benefits for cognitive functioning. Although the feasibility of home-based interventions was demonstrated, we identified areas for improvement in the future, such as setting up more efficient session themes. Further research is required to identify the effectiveness of an improved cognitive intervention involving the act of asking questions.

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Financial inclusion and financial gerontology in Japan's aging society

Kinoshita S., Komamura K., Kishimoto T.

BioScience Trends （特定非営利活動法人バイオ＆ソーシャル・サイエンス推進国際研究交流会） 18 （ 5 ） 492 - 494 2024年

ISSN 18817815

Japan, the world's most rapidly aging society, faces increasing financial strains related to personalized dementia care. The government has shifted its focus from prevention to coexistence with dementia, as outlined in the 2023 Basic Act on Dementia. Emphasis on financial inclusion aligns with the G20's 2019 “Fukuoka Policy Priorities on Aging and Financial Inclusion", which addresses financial exclusion due to cognitive decline and poor financial literacy. While economic activity among older adults is already hampered by legal challenges and risks associated with dementia, outcomes are expected to worsen as the assets of older adults with dementia are projected to reach 215 trillion JPY ($1.4 trillion USD) by 2030. Government measures and research in financial gerontology advocate for protecting older adults and promoting flexible financial practices. Enhanced efforts and shared research outcomes are crucial for Japan to be a leader as an advanced aging society.

Associations between glycemic variability, sleep quality, and daily steps in subjects without diabetes using wearable devices.

Inaishi J, Kashiwagi K, Kinoshita S, Wada Y, Hanashiro S, Shiga K, Kitazawa M, Tsutsumi S, Yamakawa H, Kishimoto T

Metabolism open 20 100263 2023年12月

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The relationship between sleep, gut microbiota, and metabolome in patients with depression and anxiety: A secondary analysis of the observational study

Tanaka A., Sanada K., Miyaho K., Tachibana T., Kurokawa S., Ishii C., Noda Y., Nakajima S., Fukuda S., Mimura M., Kishimoto T., Iwanami A.

PLoS ONE （PLoS ONE） 18 （ 12 December ） e0296047 2023年12月

ISSN 1932-6203

Background Growing attention is paid to the association between alterations in the gut microbiota and their metabolites in patients with psychiatric disorders. Our study aimed to determine how gut microbiota and metabolomes are related to the sleep quality among patients with depression and anxiety disorders by analyzing the datasets of our previous study. Methods Samples were collected from 40 patients (depression: 32 patients [80.0%]); anxiety disorders: 8 patients [20.0%]) in this study. Gut microbiomes were analyzed using 16S rRNA gene sequencing and gut metabolomes were analyzed by a mass spectrometry approach. Based on the Pittsburgh Sleep Quality Index (PSQI), patients were categorized into two groups: the insomnia group (PSQI score ≥ 9, n = 20) and the non-insomnia group (PSQI score < 9, n = 20). Results The insomnia group showed a lower alpha diversity in the Chao1 and Shannon indices than the non-insomnia group after the false discovery rate (FDR) correction. The relative abundance of genus Bacteroides showed a positive correlation with PSQI scores in the non-insomnia group. The concentrations of glucosamine and N-methylglutamate were significantly higher in the insomnia group than in the non-insomnia group. Conclusions Our findings suggest that specific taxa could affect the sleep quality among patients with depression and anxiety disorders. Further studies are needed to elucidate the impact of sleep on specific gut microbiota and metabolomes in depression and anxiety disorders.

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Introduction to Evidence-Based Digital Interventions and Informatics Approaches to Service Delivery for Behavioral Health Populations

Hilty D.M., Ahuja S., Felker B.L., Kishimoto T., Krupinski E.A.

Journal of Technology in Behavioral Science （Journal of Technology in Behavioral Science） 8 （ 4 ） 333 - 335 2023年12月

Technology use is ubiquitous in the digital age, and to ensure quality care, patients, more research, and evaluation are needed of digital interventions and informatics approaches for behavioral health disorders—particularly those that have population-level impact. Clinicians, teams, organizations, and countries have to prioritize and implement systems to organize clinical care and set the stage for evidence-based interventions. Much of this is through electronic health records (EHRs), patient portals, artificial intelligence (AI), and data analytic approaches for workflow (e.g., clinical decision support). The Special Edition is geared to help clinicians/faculty, trainees, and healthcare leaders improve clinical care, by showcasing new systems, technologies, research, and evidence- and consensus-based best practices. One overarching goal is to apply the most recent health technology and evidence to promote behavioral health and to predict, assess, triage, and treat behavioral health disorders. Another goal is to describe how to shift from in-person/video care visits to longitudinal, in time care with patient and clinician decision support facilitated by artificial intelligence and other technologies. The issue focuses on effectiveness and implementation science approaches for patients across populations and settings. Evaluation of intended and unintended consequences of new technologies could facilitate or impede workflow and outcomes.

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Electroconvulsive therapy-induced volumetric brain changes converge on a common causal circuit in depression

Argyelan, M; Deng, ZD; Ousdal, OT; Oltedal, L; Angulo, B; Baradits, M; Spitzberg, AJ; Kessler, U; Sartorius, A; Dols, A; Narr, KL; Espinoza, R; van Waarde, JA; Tendolkar, I; van Eijndhoven, P; van Wingen, GA; Takamiya, A; Kishimoto, T; Jorgensen, MB; Jorgensen, A; Paulson, OB; Yrondi, A; Péran, P; Soriano-Mas, C; Cardoner, N; Cano, M; van Diermen, L; Schrijvers, D; Belge, JB; Emsell, L; Bouckaert, F; Vandenbulcke, M; Kiebs, M; Hurlemann, R; Mulders, PCR; Redlich, R; Dannlowski, U; Erhan, K; Kritzer, MD; Ellard, KK; Camprodon, JA; Petrides, G; Malhotra, AK; Abbott, CC

MOLECULAR PSYCHIATRY 2023年11月

ISSN 1359-4184

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Electroconvulsive therapy-induced volumetric brain changes converge on a common causal circuit in depression.

Argyelan M, Deng ZD, Ousdal OT, Oltedal L, Angulo B, Baradits M, Spitzberg AJ, Kessler U, Sartorius A, Dols A, Narr KL, Espinoza R, van Waarde JA, Tendolkar I, van Eijndhoven P, van Wingen GA, Takamiya A, Kishimoto T, Jorgensen MB, Jorgensen A, Paulson OB, Yrondi A, Péran P, Soriano-Mas C, Cardoner N, Cano M, van Diermen L, Schrijvers D, Belge JB, Emsell L, Bouckaert F, Vandenbulcke M, Kiebs M, Hurlemann R, Mulders PC, Redlich R, Dannlowski U, Kavakbasi E, Kritzer MD, Ellard KK, Camprodon JA, Petrides G, Malhotra AK, Abbott CC

Molecular psychiatry 2023年11月

ISSN 1359-4184

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Efficacy and Acceptability of Remote Cognitive Behavioral Therapy for Patients With Major Depressive Disorder in Japanese Clinical Settings: A Case Series

Nogami W., Nakagawa A., Kato N., Sasaki Y., Kishimoto T., Horikoshi M., Mimura M.

Cognitive and Behavioral Practice （Cognitive and Behavioral Practice） 30 （ 4 ） 635 - 645 2023年11月

ISSN 10777229

Remote cognitive and behavioral therapy (CBT) via videoconference has been garnering attention as a means of improving access to CBT for depression, in particular during the coronavirus disease 2019 pandemic. However, there is a lack of evidence supporting its implementation in Japanese clinical settings. This case series aimed to establish preliminary evidence of whether remote CBT can be an effective therapy for major depression in Japanese clinical settings. Five patients who met the diagnostic criteria for major depressive disorder were enrolled and underwent remote CBT via videoconference and face-to-face assessment interviews. The results showed that remote CBT via videoconference improved depressive symptoms, enabling a relatively high level of patient satisfaction and working alliance. Moreover, detailed feedback from our patients showed that continuous monitoring was preferable for increasing treatment engagement. Further research is warranted to test the efficacy and acceptability of remote CBT via videoconference for treating major depression.

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精神科で本当に必要な薬は何か?　精神科領域の安定確保医薬品に関する意識調査

稲垣中, 橋本亮太, 稲田健, 坪井貴嗣, 三島和夫, 小路純央, 齊尾武郎, 安田由華, 横井優磨, 小田陽彦, 加藤正樹, 岸田郁子, 岸本泰士郎, 齊藤卓弥, 冨田哲, 古郡規雄, 松尾幸治, 渡邊衡一郎, 木下利彦, 三木和平, 三野進, 三村將

精神神経学雑誌（(公社)日本精神神経学会） 125 （ 11 ） 932 - 943 2023年11月

ISSN 0033-2658

近年,医薬品の安定供給に疑念を抱かせるような事例が多発するようになったため,2020年に厚生労働省は10種類の向精神薬を含めた506種類の安定確保医薬品を指定した.しかしながら,このときには時間的な制約から精神科のステークホルダー全体のコンセンサスに基づいて10種類の向精神薬を選定できず,少数のエキスパートたちのコンセンサスに基づいて決定せざるをえなかった.今回われわれは精神科医,薬剤師,当事者・家族を対象としたweb媒体のアンケート調査を実施したうえで,第118回日本精神神経学会学術総会の際に開催されたシンポジウムにおいてデルファイ法に準じた方法により精神科のステークホルダー全体を反映したコンセンサスの形成を試みた.アンケート調査の結果,精神科医,薬剤師,当事者・家族の大半が10種類の向精神薬を安定確保医薬品に指定することを容認していることが示された.また,デルファイ法に準じた方法による意見集約の結果,リスペリドン,アリピプラゾール,オランザピン,クエチアピン,ミルタザピン,エスシタロプラム,バルプロ酸ナトリウム,炭酸リチウム,ロラゼパム,レンボレキサントの10種類の向精神薬がより妥当な安定確保医薬品として選択された.(著者抄録)

The now and future of ChatGPT and GPT in psychiatry

Cheng S.W., Chang C.W., Chang W.J., Wang H.W., Liang C.S., Kishimoto T., Chang J.P.C., Kuo J.S., Su K.P.

Psychiatry and Clinical Neurosciences （Psychiatry and Clinical Neurosciences） 77 （ 11 ） 592 - 596 2023年11月

ISSN 13231316

ChatGPT has sparked extensive discussions within the healthcare community since its November 2022 release. However, potential applications in the field of psychiatry have received limited attention. Deep learning has proven beneficial to psychiatry, and GPT is a powerful deep learning-based language model with immense potential for this field. Despite the convenience of ChatGPT, this advanced chatbot currently has limited practical applications in psychiatry. It may be used to support psychiatrists in routine tasks such as completing medical records, facilitating communications between clinicians and with patients, polishing academic writings and presentations, and programming and performing analyses for research. The current training and application of ChatGPT require using appropriate prompts to maximize appropriate outputs and minimize deleterious inaccuracies and phantom errors. Moreover, future GPT advances that incorporate empathy, emotion recognition, personality assessment, and detection of mental health warning signs are essential for its effective integration into psychiatric care. In the near future, developing a fully-automated psychotherapy system trained for expert communication (such as psychotherapy verbatim) is conceivable by building on foundational GPT technology. This dream system should integrate practical ‘real world’ inputs and friendly AI user and patient interfaces via clinically validated algorithms, voice comprehension/generation modules, and emotion discrimination algorithms based on facial expressions and physiological inputs from wearable devices. In addition to the technology challenges, we believe it is critical to establish generally accepted ethical standards for applying ChatGPT-related tools in all mental healthcare environments, including telemedicine and academic/training settings.

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特集遠隔医療,オンライン診療の現在と未来精神科領域のオンライン診療とAI利用

木下翔太郎, 岸本泰士郎

医学のあゆみ（医歯薬出版） 287 （ 2 ） 130 - 134 2023年10月

ISSN 00392359

Assessment of glycemic variability and lifestyle behaviors in healthy nondiabetic individuals according to the categories of body mass index

Kashiwagi K., Inaishi J., Kinoshita S., Wada Y., Hanashiro S., Shiga K., Kitazawa M., Tsutsumi S., Yamakawa H., Irie J., Kishimoto T.

PLoS ONE （PLoS ONE） 18 （ 10 October ） e0291923 2023年10月

ISSN 1932-6203

Background There are limited data about the association between body mass index (BMI), glycemic variability (GV), and life-related factors in healthy nondiabetic adults. Methods This cross-sectional study was carried out within our ethics committee-approved study called “Exploring the impact of nutrition advice on blood sugar and psychological status using continuous glucose monitoring (CGM) and wearable devices”. Prediabetes was defined by the HbA1c level of 5.7–6.4% and /or fasting glucose level of 100–125 mg/dL. Glucose levels and daily steps were measured for 40 participants using Free Style Libre and Fitbit Inspire 2 under normal conditions for 14 days. Dietary intakes and eating behaviors were assessed using a brief-type self-administered dietary history questionnaire and a modified questionnaire from the Obesity Guidelines. Results All indices of GV were higher in the prediabetes group than in the healthy group, but a significant difference was observed only in mean amplitude of glycemic excursions (MAGE). In the multivariate analysis, only the presence of prediabetes showed a significant association with the risk of higher than median MAGE (Odds, 6.786; 95% CI, 1.596–28.858; P = 0.010). Additionally, the underweight (BMI < 18.5) group had significantly higher value in standard deviation (23.7 ± 3.5 vs 19.8 ± 3.7 mg/dL, P = 0.038) and coefficient variability (22.6 ± 4.6 vs 18.4 ± 3.2%, P = 0.015), compared to the normal group. This GV can be partially attributed to irregularity of eating habits. On the contrary, the overweight (BMI > 25) group had the longest time above the 140 or 180 mg/dL range, which may be due to eating style and taking fewer steps (6394 ± 2337 vs 9749 ± 2408 steps, P = 0.013). Conclusions Concurrent CGM with diet and activity monitoring could reduce postprandial hyperglycemia through assessment of diet and daily activity, especially in non- normal weight individuals.

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Effect of education regarding treatment guidelines for schizophrenia and depression on the treatment behavior of psychiatrists: A multicenter study

Hasegawa N., Yasuda Y., Yasui-Furukori N., Yamada H., Hori H., Ichihashi K., Takaesu Y., Iida H., Muraoka H., Kodaka F., Iga J.i., Hashimoto N., Ogasawara K., Ohi K., Fukumoto K., Numata S., Tsuboi T., Usami M., Hishimoto A., Furihata R., Kishimoto T., Nakamura T., Katsumoto E., Ochi S., Nagasawa T., Atake K., Kubota C., Komatsu H., Yamagata H., Ide K., Takeshima M., Kido M., Kikuchi S., Okada T., Matsumoto J., Miura K., Shimazu T., Inada K., Watanabe K., Hashimoto R.

Psychiatry and Clinical Neurosciences （Psychiatry and Clinical Neurosciences） 77 （ 10 ） 559 - 568 2023年10月

ISSN 13231316

Aim: This study aims to examine the real-world effectiveness of education regarding clinical guidelines for psychiatric disorders using ‘the Effectiveness of guidelines for dissemination and education in psychiatric treatment (EGUIDE)’ project. Methods: The EGUIDE project is a nationwide prospective implementation study of two clinical practice guidelines, i.e., the Guideline for Pharmacological Therapy of Schizophrenia and the Treatment Guidelines for Major Depressive Disorders, in Japan. Between 2016 and 2019, 782 psychiatrists belonging to 176 hospitals with psychiatric wards participated in the project and attended lectures on clinical practice guidelines. The proportions of guideline-recommended treatments in 7405 patients with schizophrenia and 3794 patients with major depressive disorder at participating hospitals were compared between patients under the care of psychiatrists participating in the project and those not participating in the project. Clinical and prescribing data on the patients discharged from April to September each year from participating hospitals of the project were also analyzed. Results: The proportions of three quality indicators (antipsychotic monotherapy regardless of whether other psychotropics medication, antipsychotic monotherapy without other psychotropics and no prescription of anxiolytics or hypnotics) for schizophrenia were higher among participating psychiatrists than among nonparticipating psychiatrists. As similar results were obtained in major depressive disorder, the effectiveness of the project for the dissemination of guideline-recommended treatment has been replicated. Conclusion: This strategy of providing education regarding the clinical guidelines for psychiatric disorders was effective in improving the treatment-related behavior of psychiatrists. The use of this education-based strategy might contribute to resolving the mental health treatment gap.

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Telepsychiatry versus face-to-face treatment: Systematic review and meta-analysis of randomised controlled trials

Hagi K., Kurokawa S., Takamiya A., Fujikawa M., Kinoshita S., Iizuka M., Furukawa S., Eguchi Y., Kishimoto T.

British Journal of Psychiatry （British Journal of Psychiatry） 223 （ 3 ） 407 - 414 2023年09月

ISSN 00071250

Background The COVID-19 pandemic has transformed healthcare significantly and telepsychiatry is now the primary means of treatment in some countries. Aims To compare the efficacy of telepsychiatry and face-to-face treatment. Method A comprehensive meta-analysis comparing telepsychiatry with face-to-face treatment for psychiatric disorders. The primary outcome was the mean change in the standard symptom scale scores used for each psychiatric disorder. Secondary outcomes included all meta-analysable outcomes, such as all-cause discontinuation and safety/tolerability. Results We identified 32 studies (n = 3592 participants) across 11 mental illnesses. Disease-specific analyses showed that telepsychiatry was superior to face-to-face treatment regarding symptom improvement for depressive disorders (k = 6 studies, n = 561; standardised mean difference s.m.d. = -0.325, 95% CI -0.640 to -0.011, P = 0.043), whereas face-to-face treatment was superior to telepsychiatry for eating disorder (k = 1, n = 128; s.m.d. = 0.368, 95% CI 0.018-0.717, P = 0.039). No significant difference was seen between telepsychiatry and face-to-face treatment when all the studies/diagnoses were combined (k = 26, n = 2290; P = 0.248). Telepsychiatry had significantly fewer all-cause discontinuations than face-to-face treatment for mild cognitive impairment (k = 1, n = 61; risk ratio RR = 0.552, 95% CI 0.312-0.975, P = 0.040), whereas the opposite was seen for substance misuse (k = 1, n = 85; RR = 37.41, 95% CI 2.356-594.1, P = 0.010). No significant difference regarding all-cause discontinuation was seen between telepsychiatry and face-to-face treatment when all the studies/diagnoses were combined (k = 27, n = 3341; P = 0.564). Conclusions Telepsychiatry achieved a symptom improvement effect for various psychiatric disorders similar to that of face-to-face treatment. However, some superiorities/inferiorities were seen across a few specific psychiatric disorders, suggesting that its efficacy may vary according to disease type.

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Development and acceptability testing of a decision aid for considering whether to reduce antipsychotics in individuals with stable schizophrenia

Aoki Y., Takaesu Y., Matsui K., Tokumasu T., Tani H., Takekita Y., Kanazawa T., Kishimoto T., Tarutani S., Hashimoto N., Takeuchi H., Mishima K., Inada K.

Neuropsychopharmacology Reports （Neuropsychopharmacology Reports） 43 （ 3 ） 391 - 402 2023年09月

Aim: Continued antipsychotic treatment is the key to preventing relapse. Maintenance antipsychotic monotherapy and optimal dose use are recommended for individuals with stable schizophrenia because of their undesirable effects. Decision aids (DAs) are clinical conversation tools that facilitate shared decision-making (SDM) between patients and health-care providers. This study aimed to describe the development process and results of acceptability testing of a DA for individuals with stable schizophrenia, considering (i) whether to continue high-dose antipsychotics or reduce to the standard dose and (ii) whether to continue two antipsychotics or shift to monotherapy. Methods: A DA was developed according to the guidelines for the appropriate use of psychotropic medications and International Patient Decision Aid Standards (IPDAS). First, a DA prototype was developed based on a previous systematic review and meta-analysis conducted for identifying the effects of continuing or reducing antipsychotic treatment. Second, mixed-method survey was performed among individuals with schizophrenia and health-care providers to modify and finalize the DA. Results: The DA consisted of an explanation of schizophrenia, options to continue high-dose antipsychotics or reduce to the standard dose, options to continue two antipsychotics or shift to monotherapy, pros and cons of each option, and a value-clarification worksheet for each option. The patients (n = 20) reported acceptable language use (75%), adequate information (75%), and well-balanced presentation (79%). Health-care providers (n = 20) also provided favorable overall feedback. The final DA covered six IPDAS qualifying criteria. Conclusion: A DA was successfully developed for schizophrenia, considering whether to reduce antipsychotics, which can be used in the SDM process.

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Efficacy and safety/tolerability of antipsychotics in the treatment of adult patients with major depressive disorder: A systematic review and meta-analysis

Kishimoto T., Hagi K., Kurokawa S., Kane J.M., Correll C.U.

Psychological Medicine （Psychological Medicine） 53 （ 9 ） 4064 - 4082 2023年07月

ISSN 00332917

Background Antipsychotics are widely used in the treatment of major depressive disorder (MDD), but there has been no comprehensive meta-analytic assessment that examined their use as monotherapy and adjunctive therapy. Methods A systematic review and a meta-analysis were conducted on randomized placebo-controlled trials (RCTs) that reported on the efficacy and safety/tolerability of antipsychotics for the treatment of adults with MDD. Data of both monotherapy and adjunctive antipsychotic use were extracted, but analyzed separately using a random-effects model. Co-primary outcomes were study-defined-treatment response and intolerability-related discontinuation. We also illustrated the risk/benefit balance of antipsychotics for MDD, using two-dimensional graphs representing the primary efficacy and safety/tolerability outcome. Secondary outcomes included psychopathology, remission, all-cause-discontinuation, inefficacy-related discontinuation, and adverse events. Results Forty-five RCTs with 12 724 patients were included in the analysis. In monotherapy (studies = 13, n = 4375), amisulpride [1.99 (1.55-2.55)], sulpiride [1.50 (1.03-2.17)], and quetiapine [1.48 (1.23-1.78)] were significantly superior to placebo regarding treatment response. However, intolerability-related discontinuations were significantly higher compared to placebo with amisulpride and quetiapine. In adjunctive therapy (studies = 32, n = 8349), ziprasidone [1.80 (1.07-3.04)], risperidone [1.59 (1.19-2.14)], aripiprazole [1.54 (1.35-1.76)], brexpiprazole [1.41 (1.21-1.66)], cariprazine [1.27 (1.07-1.52)], and quetiapine [1.23 (1.08-1.41)] were significantly superior to placebo regarding treatment response. However, of these antipsychotics that were superior to placebo, only risperidone was equivalent to placebo regarding discontinuation due to intolerability, while the other antipsychotics were inferior. Conclusion Results suggest that there are significant differences regarding the risk/benefit ratio among antipsychotics for MDD, which should inform clinical care.

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Detecting Dementia from Face-Related Features with Automated Computational Methods

Zheng C., Bouazizi M., Ohtsuki T., Kitazawa M., Horigome T., Kishimoto T.

Bioengineering （Bioengineering） 10 （ 7 ） 2023年07月

ISSN 2306-5354

Alzheimer’s disease (AD) is a type of dementia that is more likely to occur as people age. It currently has no known cure. As the world’s population is aging quickly, early screening for AD has become increasingly important. Traditional screening methods such as brain scans or psychiatric tests are stressful and costly. The patients are likely to feel reluctant to such screenings and fail to receive timely intervention. While researchers have been exploring the use of language in dementia detection, less attention has been given to face-related features. The paper focuses on investigating how face-related features can aid in detecting dementia by exploring the PROMPT dataset that contains video data collected from patients with dementia during interviews. In this work, we extracted three types of features from the videos, including face mesh, Histogram of Oriented Gradients (HOG) features, and Action Units (AU). We trained traditional machine learning models and deep learning models on the extracted features and investigated their effectiveness in dementia detection. Our experiments show that the use of HOG features achieved the highest accuracy of 79% in dementia detection, followed by AU features with 71% accuracy, and face mesh features with 66% accuracy. Our results show that face-related features have the potential to be a crucial indicator in automated computational dementia detection.

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Electroconvulsive therapy-induced volumetric brain changes converge on a common causal circuit in depression.

Deng ZD, Ousdal OT, Oltedal L, Angulo B, Baradits M, Spitzberg A, Kessler U, Sartorius A, Dols A, Narr K, Espinoza R, Van Waarde J, Tendolkar I, van Eijndhoven P, van Wingen G, Takamiya A, Kishimoto T, Jorgensen M, Jorgensen A, Paulson O, Yrondi A, Peran P, Soriano-Mas C, Cardoner N, Cano M, van Diermen L, Schrijvers D, Belge JB, Emsell L, Bouckaert F, Vandenbulcke M, Kiebs M, Hurlemann R, Mulders P, Redlich R, Dannlowski U, Kavakbasi E, Kritzer M, Ellard K, Camprodon J, Petrides G, Maholtra A, Abbott C, Argyelan M

Research square 2023年06月

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Language patterns in Japanese patients with Alzheimer disease: A machine learning approach

Momota Y., Liang K.c., Horigome T., Kitazawa M., Eguchi Y., Takamiya A., Goto A., Mimura M., Kishimoto T.

Psychiatry and Clinical Neurosciences （Psychiatry and Clinical Neurosciences） 77 （ 5 ） 273 - 281 2023年05月

ISSN 13231316

Aim: The authors applied natural language processing and machine learning to explore the disease-related language patterns that warrant objective measures for assessing language ability in Japanese patients with Alzheimer disease (AD), while most previous studies have used large publicly available data sets in Euro-American languages. Methods: The authors obtained 276 speech samples from 42 patients with AD and 52 healthy controls, aged 50 years or older. A natural language processing library for Python was used, spaCy, with an add-on library, GiNZA, which is a Japanese parser based on Universal Dependencies designed to facilitate multilingual parser development. The authors used eXtreme Gradient Boosting for our classification algorithm. Each unit of part-of-speech and dependency was tagged and counted to create features such as tag-frequency and tag-to-tag transition-frequency. Each feature's importance was computed during the 100-fold repeated random subsampling validation and averaged. Results: The model resulted in an accuracy of 0.84 (SD = 0.06), and an area under the curve of 0.90 (SD = 0.03). Among the features that were important for such predictions, seven of the top 10 features were related to part-of-speech, while the remaining three were related to dependency. A box plot analysis demonstrated that the appearance rates of content words–related features were lower among the patients, whereas those with stagnation-related features were higher. Conclusion: The current study demonstrated a promising level of accuracy for predicting AD and found the language patterns corresponding to the type of lexical-semantic decline known as ‘empty speech’, which is regarded as a characteristic of AD.

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Validation of the Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) questionnaire for adults

Solmi M., Thompson T., Estradé A., Agorastos A., Radua J., Cortese S., Dragioti E., Leisch F., Vancampfort D., Thygesen L.C., Aschauer H., Schlögelhofer M., Aschauer E., Schneeberger A., Huber C.G., Hasler G., Conus P., Do Cuénod K.Q., von Känel R., Arrondo G., Fusar-Poli P., Gorwood P., Llorca P.M., Krebs M.O., Scanferla E., Kishimoto T., Rabbani G., Skonieczna-Żydecka K., Brambilla P., Favaro A., Takamiya A., Zoccante L., Colizzi M., Bourgin J., Kamiński K., Moghadasin M., Seedat S., Matthews E., Wells J., Vassilopoulou E., Gadelha A., Su K.P., Kwon J.S., Kim M., Lee T.Y., Papsuev O., Manková D., Boscutti A., Gerunda C., Saccon D., Righi E., Monaco F., Croatto G., Cereda G., Demurtas J., Brondino N., Veronese N., Enrico P., Politi P., Ciappolino V., Pfennig A., Bechdolf A., Meyer-Lindenberg A., Kahl K.G., Domschke K., Bauer M., Koutsouleris N., Winter S., Borgwardt S., Bitter I., Balazs J., Czobor P., Unoka Z., Mavridis D., Tsamakis K., Bozikas V.P., Tunvirachaisakul C., Maes M., Rungnirundorn T., Supasitthumrong T., Haque A., Brunoni A.R., Costardi C.G., Schuch F.B., Polanczyk G., Luiz J.M., Fonseca L., Aparicio L.V., Valvassori S.S., Nordentoft M., Vendsborg P., Hoffmann S.H., Sehli J., Sartorius N., Heuss S., Guinart D., Hamilton J., Kane J., Rubio J., Sand M.

Journal of Affective Disorders （Journal of Affective Disorders） 326 249 - 261 2023年04月

ISSN 01650327

Background: The Collaborative Outcome study on Health and Functioning during Infection Times (COH-FIT; www.coh-fit.com) is an anonymous and global online survey measuring health and functioning during the COVID-19 pandemic. The aim of this study was to test concurrently the validity of COH-FIT items and the internal validity of the co-primary outcome, a composite psychopathology “P-score”. Methods: The COH-FIT survey has been translated into 30 languages (two blind forward-translations, consensus, one independent English back-translation, final harmonization). To measure mental health, 1–4 items (“COH-FIT items”) were extracted from validated questionnaires (e.g. Patient Health Questionnaire 9). COH-FIT items measured anxiety, depressive, post-traumatic, obsessive-compulsive, bipolar and psychotic symptoms, as well as stress, sleep and concentration. COH-FIT Items which correlated r ≥ 0.5 with validated companion questionnaires, were initially retained. A P-score factor structure was then identified from these items using exploratory factor analysis (EFA) and confirmatory factor analyses (CFA) on data split into training and validation sets. Consistency of results across languages, gender and age was assessed. Results: From >150,000 adult responses by May 6th, 2022, a subset of 22,456 completed both COH-FIT items and validated questionnaires. Concurrent validity was consistently demonstrated across different languages for COH-FIT items. CFA confirmed EFA results of five first-order factors (anxiety, depression, post-traumatic, psychotic, psychophysiologic symptoms) and revealed a single second-order factor P-score, with high internal reliability (ω = 0.95). Factor structure was consistent across age and sex. Conclusions: COH-FIT is a valid instrument to globally measure mental health during infection times. The P-score is a valid measure of multidimensional mental health.

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Dectin-1 signaling on colonic γδ T cells promotes psychosocial stress responses

Zhu X., Sakamoto S., Ishii C., Smith M.D., Ito K., Obayashi M., Unger L., Hasegawa Y., Kurokawa S., Kishimoto T., Li H., Hatano S., Wang T.H., Yoshikai Y., Kano S.i., Fukuda S., Sanada K., Calabresi P.A., Kamiya A.

Nature Immunology （Nature Immunology） 24 （ 4 ） 625 - 636 2023年04月

ISSN 15292908

The intestinal immune system interacts with commensal microbiota to maintain gut homeostasis. Furthermore, stress alters the microbiome composition, leading to impaired brain function; yet how the intestinal immune system mediates these effects remains elusive. Here we report that colonic γδ T cells modulate behavioral vulnerability to chronic social stress via dectin-1 signaling. We show that reduction in specific Lactobacillus species, which are involved in T cell differentiation to protect the host immune system, contributes to stress-induced social-avoidance behavior, consistent with our observations in patients with depression. Stress-susceptible behaviors derive from increased differentiation in colonic interleukin (IL)-17-producing γδ T cells (γδ17 T cells) and their meningeal accumulation. These stress-susceptible cellular and behavioral phenotypes are causally mediated by dectin-1, an innate immune receptor expressed in γδ T cells. Our results highlight the previously unrecognized role of intestinal γδ17 T cells in the modulation of psychological stress responses and the importance of dectin-1 as a potential therapeutic target for the treatment of stress-induced behaviors.

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Development of an individual fitness score (IFS) based on the depression treatment guidelines of in the Japanese Society of Mood Disorders

Fukumoto K., Kodaka F., Hasegawa N., Muraoka H., Hori H., Ichihashi K., Yasuda Y., Iida H., Ohi K., Ochi S., Ide K., Hashimoto N., Usami M., Nakamura T., Komatsu H., Okada T., Nagasawa T., Furihata R., Atake K., Kido M., Kikuchi S., Yamagata H., Kishimoto T., Makinodan M., Horai T., Takeshima M., Kubota C., Asami T., Katsumoto E., Hishimoto A., Onitsuka T., Matsumoto J., Miura K., Yamada H., Yasui-Furukori N., Watanabe K., Inada K., Otsuka K., Hashimoto R.

Neuropsychopharmacology Reports （Neuropsychopharmacology Reports） 43 （ 1 ） 33 - 39 2023年03月

Aim: Treatment guidelines are designed to assist patients and health care providers and are used as tools for making treatment decisions in clinical situations. The treatment guidelines of the Japanese Society of Mood Disorders establish treatment recommendations for each severity of depression. The individual fitness score (IFS) was developed as a simple and objective indicator to assess whether individual patients are practicing treatment by the recommendations of the depression treatment guidelines of the Japanese Society of Mood Disorders. Methods: The EGUIDE project members determined the IFS through the modified Delphi method. In this article, the IFS was calculated based on the treatment of depressed patients treated and discharged between 2016 and 2020 at facilities participating in the EGUIDE project. In addition, we compared scores at admission and discharge. Results: The study included 428 depressed patients (mild n = 22, moderate/severe n = 331, psychotic n = 75) at 57 facilities. The mean IFS scores by severity were statistically significantly higher at discharge than at admission with moderate/severe depression (mild 36.1 ± 34.2 vs. 41.6 ± 36.9, p = 0.49; moderate/severe 50.2 ± 33.6 vs. 55.7 ± 32.6, p = 2.1 × 10–3; psychotic 47.4 ± 32.9 versus 52.9 ± 36.0, p = 0.23). Conclusion: We developed the IFS based on the depression treatment guideline, which enables us to objectively determine how close the treatment is to the guideline at the time of evaluation in individual cases. Therefore, the IFS may influence guideline-oriented treatment behavior and lead to the equalization of depression treatment in Japan, including pharmacotherapy.

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A Sphrical Waterflow Vector Sensor in Deep Sea

Kishimoto, T; Matsudaira, K; Tanaka, H; Takahashi, H

2023 IEEE SENSORS 2023年

ISSN 1930-0395

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Electroconvulsive therapy-induced volumetric brain changes converge on a common causal circuit in depression

Argyelan M., Deng Z.D., Ousdal O.T., Oltedal L., Angulo B., Baradits M., Spitzberg A.J., Kessler U., Sartorius A., Dols A., Narr K.L., Espinoza R., van Waarde J.A., Tendolkar I., van Eijndhoven P., van Wingen G.A., Takamiya A., Kishimoto T., Jorgensen M.B., Jorgensen A., Paulson O.B., Yrondi A., Péran P., Soriano-Mas C., Cardoner N., Cano M., van Diermen L., Schrijvers D., Belge J.B., Emsell L., Bouckaert F., Vandenbulcke M., Kiebs M., Hurlemann R., Mulders P.C., Redlich R., Dannlowski U., Erhan K., Kritzer M.D., Ellard K.K., Camprodon J.A., Petrides G., Malhotra A.K., Abbott C.C.

Molecular Psychiatry （Molecular Psychiatry） 2023年

ISSN 13594184

Neurostimulation is a mainstream treatment option for major depression. Neuromodulation techniques apply repetitive magnetic or electrical stimulation to some neural target but significantly differ in their invasiveness, spatial selectivity, mechanism of action, and efficacy. Despite these differences, recent analyses of transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS)-treated individuals converged on a common neural network that might have a causal role in treatment response. We set out to investigate if the neuronal underpinnings of electroconvulsive therapy (ECT) are similarly associated with this causal depression network (CDN). Our aim here is to provide a comprehensive analysis in three cohorts of patients segregated by electrode placement (N = 246 with right unilateral, 79 with bitemporal, and 61 with mixed) who underwent ECT. We conducted a data-driven, unsupervised multivariate neuroimaging analysis Principal Component Analysis (PCA) of the cortical and subcortical volume changes and electric field (EF) distribution to explore changes within the CDN associated with antidepressant outcomes. Despite the different treatment modalities (ECT vs TMS and DBS) and methodological approaches (structural vs functional networks), we found a highly similar pattern of change within the CDN in the three cohorts of patients (spatial similarity across 85 regions: r = 0.65, 0.58, 0.40, df = 83). Most importantly, the expression of this pattern correlated with clinical outcomes (t = −2.35, p = 0.019). This evidence further supports that treatment interventions converge on a CDN in depression. Optimizing modulation of this network could serve to improve the outcome of neurostimulation in depression.

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診断付き精神疾患会話コーパスを用いたうつ病の重症度自動分類と特徴量分析

香月祥, 田中宏和, 中村啓信, 岸本泰士郎, 狩野芳伸

人工知能学会全国大会論文集（一般社団法人人工知能学会） JSAI2023 （ 0 ） 4Xin150 - 4Xin150 2023年

我々はこれまで、診断や疾患評価、音声とその文字起こしや音声・言語学的アノテーションが付与されたUNDERPIN大規模精神疾患会話コーパスを構築してきた。このコーパスを用いて、うつ病患者の分類実験を行った。分類の際は、健常者・軽症患者・中等度以上の患者・うつ病と診断されたことがあるがテストの評価値で症状のない患者の4分類を設定し、4分類のすべてのペア6つそれぞれで2値分類を行った。結果、軽症・中等度以上の重症度に応じた分類ができること、また現在の症状にかかわらずうつ病になった性質で分類可能であることを確認した。分類に貢献した特徴量の分析では、重症度ごとに異なる特徴量や共通している特徴量を確認できた。今後は、新しい特徴量を追加しての学習や、特徴のもととなった人手のアノテーションを自動付与するシステムを構築したい。

UNDERPIN精神疾患会話コーパスの構築と音声・言語特徴に基づく精神疾患の分類および特徴料分析

田中宏和, 香月祥, 中村啓伸, 岸本泰士郎, 狩野芳伸

人工知能学会全国大会論文集（一般社団法人人工知能学会） JSAI2023 （ 0 ） 3Xin480 - 3Xin480 2023年

我々は1000時間を超える録音時間の診断付き大規模精神疾患会話コーパスUNDERPINを構築してきた。コーパスは疾患名、処方薬、患者の疾患情報と、症状の観察や各種テストによる重症度評価、および対話データからなる。コーパスから抽出した音声・言語特徴量を用いて、うつ病・不安症・統合失調症・認知症・双極性障害と健常者との疾患分類を機械学習によって行ったところ、各疾患の分類性能は疾患により75-91%程度を達成した。特徴量貢献度分析の結果、フォルマント、フィラー、笑い、疑問がこれら疾患を分類するために重要な特徴であると示唆された。

Psychiatrists’ Perspectives on Advantages, Disadvantages and Challenging for Promotion Related to Telemedicine: Japan’s Clinical Experience During COVID-19 Pandemic

Kinoshita S., Kitazawa M., Abe Y., Suda A., Nakamae T., Kanazawa T., Tomita H., Hishimoto A., Kishimoto T.

Journal of Technology in Behavioral Science （Journal of Technology in Behavioral Science） 9 （ 3 ） 532 - 541 2023年

The use of telemedicine in Japan increased during the coronavirus disease pandemic, but is still limited. This study aimed to investigate the perceptions of psychiatrists regarding the use of telemedicine in psychiatry and provide insights into future measures to facilitate its widespread use in Japan. This is the first study of psychiatrists' perceptions of telemedicine in Japan that incorporates quantitative assessments. A web-based questionnaire consisting of 18 Likert scale questions and 6 open-ended questions was conducted in August 2022. Of the 67 psychiatrists who participated in a randomized control trial, initiated in Japan in April 2021 to compare the effectiveness of telemedicine with that of face-to-face treatment, 30 who were in a position to provide regular telemedicine by August 2022 were surveyed. The questionnaire was completed by all 30 psychiatrists surveyed. Ninety percent of the respondents said that telemedicine was a good use of patients’ time, and 93.4% said that it was a cost-effective way for patients to receive care. Of the respondents, 56.6% indicated that telemedicine could be used to address psychiatric problems that could not be resolved through outpatient visits, and 93.4% indicated that the use of telemedicine in clinical research is useful. In response to an open-ended question regarding obstacles to the widespread use of telemedicine, 63.3% of respondents answered that the medical fee determined by the government was inappropriate, and this was the most common response. These results highlight the utility of the use of telemedicine in psychiatry and clinical research. Therefore, more appropriate measures to promote the use of telemedicine are desired in the future.

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Modification of the therapist’s facial expressions using virtual reality technology during the treatment of social anxiety disorder: a case series

Horigome T., Yoshida S., Tanikawa T., Mimura M., Kishimoto T.

Frontiers in Psychology （Frontiers in Psychology） 14 1030050 2023年

ISSN 1664-1078

Exposure therapy is a mainstream of treatment for social anxiety disorder (SAD). However, effort and time are required to recreate interpersonal situations that produce moderate anxiety. On the other hand, virtual reality exposure therapy can easily control anxiety-inducing conditions and allow for graduated exposure. However, artificial intelligence and animations that speak as naturally as actual humans are not yet practical, adding to the limitations of these treatments. The authors propose the use of a virtual reality technology that can transform facial expressions into smiling or sad faces in real time and display them on a monitor, potentially solving the above-mentioned problems associated with virtual reality animations. This feasibility study was conducted to determine whether this system can be safely applied to the treatment of SAD patients. A total of four SAD patients received 16 exposure therapy sessions led by an experienced therapist over a monitor; throughout the sessions, the facial expressions of the therapist were modified using software to display expressions ranging from smiling to sad on the monitor that was being viewed by the patient. Client satisfaction, treatment alliance, and symptom assessments were then conducted. Although one patient dropped out of the study, treatment satisfaction and treatment alliance were scored high in all the cases. In two of the four cases, the improvement in symptoms was sustained over time. Exposure therapy in which the interviewer’s facial expressions are modified to induce appropriate levels of anxiety in the patient can be safely used for the treatment of SAD patients and may be effective for some patients.

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Live two-way video versus face-to-face treatment for depression, anxiety, and obsessive-compulsive disorder: A 24-week randomized controlled trial

Kishimoto T., Kinoshita S., Kitazawa M., Hishimoto A., Asami T., Suda A., Bun S., Kikuchi T., Sado M., Takamiya A., Mimura M., Sato Y., Takemura R., Nagashima K., Nakamae T., Abe Y., Kanazawa T., Kawabata Y., Tomita H., Abe K., Hongo S., Kimura H., Sato A., Kida H., Sakuma K., Funayama M., Sugiyama N., Hino K., Amagai T., Takamiya M., Kodama H., Goto K., Fujiwara S., Kaiya H., Nagao K.

Psychiatry and Clinical Neurosciences （Psychiatry and Clinical Neurosciences） 78 （ 4 ） 220 - 228 2023年

ISSN 13231316

Aim: Live two-way video, easily accessible from home via smartphones and other devices, is becoming a new way of providing psychiatric treatment. However, lack of evidence for real-world clinical setting effectiveness hampers its approval by medical insurance in some countries. Here, we conducted the first large-scale pragmatic, randomized controlled trial to determine the effectiveness of long-term treatment for multiple psychiatric disorders via two-way video using smartphones and other devices, which are currently the primary means of telecommunication. Methods: This randomized controlled trial compared two-way video versus face-to-face treatment for depressive disorder, anxiety disorder, and obsessive-compulsive disorder in the subacute/maintenance phase during a 24-week period. Adult patients with the above-mentioned disorders were allocated to either a two-way video group (≥50% video sessions) or a face-to-face group (100% in-person sessions) and received standard treatment covered by public medical insurance. The primary outcome was the 36-Item Short-Form Health Survey Mental Component Summary (SF-36 MCS) score. Secondary outcomes included all-cause discontinuation, working alliance, adverse events, and the severity rating scales for each disorder. Results: A total of 199 patients participated in this study. After 24 weeks of treatment, two-way video treatment was found to be noninferior to face-to-face treatment regarding SF-36 MCS score (48.50 vs 46.68, respectively; p < 0.001). There were no significant differences between the groups regarding most secondary end points, including all-cause discontinuation, treatment efficacy, and satisfaction. Conclusion: Two-way video treatment using smartphones and other devices, was noninferior to face-to-face treatment in real-world clinical settings. Modern telemedicine, easily accessible from home, can be used as a form of health care.

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Development of medical device software for the screening and assessment of depression severity using data collected from a wristband-type wearable device: SWIFT study protocol

Kishimoto T., Kinoshita S., Kikuchi T., Bun S., Kitazawa M., Horigome T., Tazawa Y., Takamiya A., Hirano J., Mimura M., Liang K.C., Koga N., Ochiai Y., Ito H., Miyamae Y., Tsujimoto Y., Sakuma K., Kida H., Miura G., Kawade Y., Goto A., Yoshino F.

Frontiers in Psychiatry （Frontiers in Psychiatry） 13 1025517 2022年12月

ISSN 1664-0640

Introduction: Few biomarkers can be used clinically to diagnose and assess the severity of depression. However, a decrease in activity and sleep efficiency can be observed in depressed patients, and recent technological developments have made it possible to measure these changes. In addition, physiological changes, such as heart rate variability, can be used to distinguish depressed patients from normal persons; these parameters can be used to improve diagnostic accuracy. The proposed research will explore and construct machine learning models capable of detecting depressive episodes and assessing their severity using data collected from wristband-type wearable devices. Methods and analysis: Patients with depressive symptoms and healthy subjects will wear a wristband-type wearable device for 7 days; data on triaxial acceleration, pulse rate, skin temperature, and ultraviolet light will be collected. On the seventh day of wearing, the severity of depressive episodes will be assessed using Structured Clinical Interview for DSM-5 (SCID-5), Hamilton Depression Rating Scale (HAMD), and other scales. Data for up to five 7-day periods of device wearing will be collected from each subject. Using wearable device data associated with clinical symptoms as supervisory data, we will explore and build a machine learning model capable of identifying the presence or absence of depressive episodes and predicting the HAMD scores for an unknown data set. Discussion: Our machine learning model could improve the clinical diagnosis and management of depression through the use of a wearable medical device. Clinical trial registration: [https://jrct.niph.go.jp/latest-detail/jRCT1031210478], identifier [jRCT1031210478].

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Understanding psychiatric illness through natural language processing (UNDERPIN): Rationale, design, and methodology

Kishimoto T., Nakamura H., Kano Y., Eguchi Y., Kitazawa M., Liang K.C., Kudo K., Sento A., Takamiya A., Horigome T., Yamasaki T., Sunami Y., Kikuchi T., Nakajima K., Tomita M., Bun S., Momota Y., Sawada K., Murakami J., Takahashi H., Mimura M.

Frontiers in Psychiatry （Frontiers in Psychiatry） 13 954703 2022年12月

ISSN 1664-0640

Introduction: Psychiatric disorders are diagnosed through observations of psychiatrists according to diagnostic criteria such as the DSM-5. Such observations, however, are mainly based on each psychiatrist's level of experience and often lack objectivity, potentially leading to disagreements among psychiatrists. In contrast, specific linguistic features can be observed in some psychiatric disorders, such as a loosening of associations in schizophrenia. Some studies explored biomarkers, but biomarkers have yet to be used in clinical practice. Aim: The purposes of this study are to create a large dataset of Japanese speech data labeled with detailed information on psychiatric disorders and neurocognitive disorders to quantify the linguistic features of those disorders using natural language processing and, finally, to develop objective and easy-to-use biomarkers for diagnosing and assessing the severity of them. Methods: This study will have a multi-center prospective design. The DSM-5 or ICD-11 criteria for major depressive disorder, bipolar disorder, schizophrenia, and anxiety disorder and for major and minor neurocognitive disorders will be regarded as the inclusion criteria for the psychiatric disorder samples. For the healthy subjects, the absence of a history of psychiatric disorders will be confirmed using the Mini-International Neuropsychiatric Interview (M.I.N.I.). The absence of current cognitive decline will be confirmed using the Mini-Mental State Examination (MMSE). A psychiatrist or psychologist will conduct 30-to-60-min interviews with each participant; these interviews will include free conversation, picture-description task, and story-telling task, all of which will be recorded using a microphone headset. In addition, the severity of disorders will be assessed using clinical rating scales. Data will be collected from each participant at least twice during the study period and up to a maximum of five times at an interval of at least one month. Discussion: This study is unique in its large sample size and the novelty of its method, and has potential for applications in many fields. We have some challenges regarding inter-rater reliability and the linguistic peculiarities of Japanese. As of September 2022, we have collected a total of >1000 records from >400 participants. To the best of our knowledge, this data sample is one of the largest in this field. Clinical Trial Registration: Identifier: UMIN000032141.

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Development of individual fitness score for conformity of prescriptions to the “Guidelines For Pharmacological Therapy of Schizophrenia”

Inada K., Fukumoto K., Hasegawa N., Yasuda Y., Yamada H., Hori H., Ichihashi K., Iida H., Ohi K., Muraoka H., Kodaka F., Ide K., Hashimoto N., Iga J.i., Ogasawara K., Atake K., Takaesu Y., Nagasawa T., Komatsu H., Okada T., Furihata R., Kido M., Kikuchi S., Kubota C., Makinodan M., Ochi S., Takeshima M., Yamagata H., Matsumoto J., Miura K., Usami M., Kishimoto T., Onitsuka T., Katsumoto E., Hishimoto A., Numata S., Yasui-Furukori N., Watanabe K., Hashimoto R.

Neuropsychopharmacology Reports （Neuropsychopharmacology Reports） 42 （ 4 ） 502 - 509 2022年12月

Aims: The Guidelines for the Pharmacotherapy of Schizophrenia were established to improve the quality of medical care, and the EGUIDE project was conducted to train clinicians on guideline usage. A quality indicator (QI) was established to measure the prevalence of the guidelines, and a survey was conducted, which revealed a gap between the guidelines and actual clinical practice (evidence-practice-gap). The purpose of this study was to develop an individual fitness score (IFS) formula that expresses the degree to which prescribers adhere to the Guidelines for Pharmacological Therapy of Schizophrenia in a simple manner, and to determine the validity of this formula from a survey of the prescriptions of the EGUIDE project participants'. Methods: To establish appropriate scores, members discussed the proposed formula and then voted on them. The IFS formula developed was set up so that antipsychotic monotherapy would be given 100 points, with points deducted if concomitant or adjunctive antipsychotic medications were used, and a minimum score of 0. To validate this formula, prescriptions of hospitalized schizophrenic patients at admission and at discharge were scored and compared. Result: IFS points vary and ranged from 0 to100. The average pre-admission score for all subjects was 45.6, and the average score at discharge was 54, those were significantly higher during discharge. Conclusions: We developed an IFS formula, a tool to easily visualize the degree to which current prescriptions conform to the guidelines for the pharmacological treatment of schizophrenia.

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The characteristics of discharge prescriptions including pro re nata psychotropic medications for patients with schizophrenia and major depressive disorder from the survey of the “Effectiveness of guidelines for dissemination and education in psychiatric treatment (EGUIDE)” project

Kyou Y., Yasui-Furukori N., Hasegawa N., Ide K., Ichihashi K., Hashimoto N., Hori H., Shimizu Y., Imamura Y., Muraoka H., Iida H., Ohi K., Yasuda Y., Ogasawara K., Numata S., Iga J.i., Tsuboi T., Ochi S., Kodaka F., Furihata R., Onitsuka T., Makinodan M., Komatsu H., Takeshima M., Kubota C., Hishimoto A., Atake K., Yamagata H., Kido M., Nagasawa T., Usami M., Kishimoto T., Kikuchi S., Matsumoto J., Miura K., Yamada H., Watanabe K., Inada K., Hahimoto R.

Annals of General Psychiatry （Annals of General Psychiatry） 21 （ 1 ） 52 2022年12月

ISSN 1744-859X

Background: Several guidelines recommend monotherapy in pharmacotherapy for schizophrenia and major depressive disorder. The content of regular prescriptions has been reported in several studies, but not enough research has been conducted on the content of pharmacotherapy, including pro re nata (PRN) medications. The purpose of this study was to evaluate the content of pharmacotherapy, including PRN medications, and to clarify the relationship with regular prescriptions. Methods: We used data from the “Effectiveness of Guidelines for Dissemination And Education in psychiatric treatment” (EGUIDE) project to investigate the presence or absence of PRN psychotropic medications at discharge for each drug category. We compared the PRN psychotropic prescription ratio at discharge by diagnosis for each drug category. The antipsychotic monotherapy ratio and no prescription ratio of other psychotropics for schizophrenia at discharge and the antidepressant monotherapy ratio and no prescription ratio of other psychotropics for major depressive disorder at discharge were calculated for each regular prescription, including PRN psychotropic medications, as quality indicators (QIs). Spearman's rank correlation test was performed for QI values of regular prescriptions and the QI ratio between regular prescriptions and prescriptions including PRN medications for each diagnosis. Results: The PRN psychotropic prescription ratio at discharge was 28.7% for schizophrenia and 30.4% for major depressive disorder, with no significant differences by diagnosis. The prescription ratios of PRN antipsychotic medications and PRN antiparkinsonian medications were significantly higher for schizophrenia. The prescription ratios of PRN anxiolytic and hypnotic and PRN antidepressant medications were significantly higher for patients with major depressive disorder. For both schizophrenia and major depressive disorder, the QI was lower for discharge prescriptions, including PRN medications, than for regular prescriptions. QI values for regular prescriptions and the QI ratio were positively correlated. Conclusions: Considering PRN psychotropic medications, the monotherapy ratio and no prescription ratio of other psychotropics at discharge decreased in pharmacotherapy for schizophrenia and major depressive disorder. A higher ratio of monotherapy and no prescription of other psychotropics on regular prescriptions may result in less concomitant use of PRN psychotropic medications. Further studies are needed to optimize PRN psychotropic prescriptions.

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Identifying neurocognitive disorder using vector representation of free conversation

Horigome T., Hino K., Toyoshiba H., Shindo N., Funaki K., Eguchi Y., Kitazawa M., Fujita T., Mimura M., Kishimoto T.

Scientific Reports （Scientific Reports） 12 （ 1 ） 12461 2022年12月

ISSN 2045-2322

In recent years, studies on the use of natural language processing (NLP) approaches to identify dementia have been reported. Most of these studies used picture description tasks or other similar tasks to encourage spontaneous speech, but the use of free conversation without requiring a task might be easier to perform in a clinical setting. Moreover, free conversation is unlikely to induce a learning effect. Therefore, the purpose of this study was to develop a machine learning model to discriminate subjects with and without dementia by extracting features from unstructured free conversation data using NLP. We recruited patients who visited a specialized outpatient clinic for dementia and healthy volunteers. Participants’ conversation was transcribed and the text data was decomposed from natural sentences into morphemes by performing a morphological analysis using NLP, and then converted into real-valued vectors that were used as features for machine learning. A total of 432 datasets were used, and the resulting machine learning model classified the data for dementia and non-dementia subjects with an accuracy of 0.900, sensitivity of 0.881, and a specificity of 0.916. Using sentence vector information, it was possible to develop a machine-learning algorithm capable of discriminating dementia from non-dementia subjects with a high accuracy based on free conversation.

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Case report: Non-Alzheimer's disease tauopathy with logopenic variant primary progressive aphasia diagnosed using amyloid and tau PET

Momota Y., Konishi M., Takahata K., Kishimoto T., Tezuka T., Bun S., Tabuchi H., Ito D., Mimura M.

Frontiers in Neurology （Frontiers in Neurology） 13 1049113 2022年11月

ISSN 1664-2295

We report a patient with logopenic variant primary progressive aphasia (lv-PPA) who was diagnosed as having non-Alzheimer's disease (AD) tauopathy after multiple biophysical/biological examinations, including amyloid and 18F-florzolotau tau positron emission tomography (PET), had been performed. A woman in her late 60s who had previously been diagnosed as having AD was referred to us for a further, detailed examination. She had been unaware of any symptoms at the time of AD diagnosis, but she subsequently became gradually aware of a speech impairment. She talked nearly completely and fluently, although she occasionally exhibited word-finding difficulty and made phonological errors during naming, word fluency testing, and sentence repetition; these findings met the criteria for the diagnosis of lv-PPA, which is known to be observed more commonly in AD than in other proteinopathies. Magnetic resonance imaging, single photon emission computed tomography, and plasma phosphorylated tau and plasma neurofilament light chain measurements showed an AD-like pattern. However, both 11C-Pittsburgh compound-B and 18F-florbetaben amyloid PET showed negative results, whereas 18F-florzolotau tau PET yielded positive results, with radio signals predominantly in the left superior temporal gyrus, middle temporal gyrus, supramarginal gyrus, and frontal operculum. Whole-genome sequencing revealed no known dominantly inherited mutations in AD or frontotemporal lobar degeneration genes, including the genes encoding amyloid precursor protein, microtubule-associated protein tau, presenilin 1 and 2. To the best of our knowledge, this patient was a rare case of lv-PPA who was diagnosed as having non-AD tauopathy based on the results of multiple examinations, including whole-genome sequencing, plasma measurement, and amyloid and 18F-florzolotau tau PET. This case underscores the clinicopathologically heterogeneous nature of this syndrome.

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The Potential Impact of Age on Gut Microbiota in Patients with Major Depressive Disorder: A Secondary Analysis of the Prospective Observational Study

Miyaho K., Sanada K., Kurokawa S., Tanaka A., Tachibana T., Ishii C., Noda Y., Nakajima S., Fukuda S., Mimura M., Kishimoto T., Iwanami A.

Journal of Personalized Medicine （Journal of Personalized Medicine） 12 （ 11 ） 2022年11月

ISSN 2075-4426

We aimed to investigate the impact of aging on the relationship among the composition of gut microbiota, gastrointestinal (GI) symptoms, and the course of treatment for major depressive disorder (MDD) by analyzing the datasets from our previous study. Patients with MDD were recruited, and their stools were collected at three time points (baseline, midterm, and endpoint) following the usual antidepressant treatment. Gut microbiota were analyzed using 16S rRNA gene sequencing. Patients were categorized into two groups based on their age: the late-life group over 60 years and the middle-aged group under 60 years. GI symptoms were assessed with scores of item 11 of the Hamilton Anxiety Rating Scale. One hundred and ninety samples were collected from 32 patients with MDD. Several gut microbes had higher relative abundances in the late-life group than in the middle-aged group. In addition, the late-life group showed significantly higher diversity in the Chao1 index at baseline compared with the middle-aged group. We further found possible microbial taxa related to GI symptoms in patients with late-life depression. The abundance of several bacterial taxa may contribute to GI symptoms in the late-life depression, and our findings suggest that the therapeutic targets for the application of gut microbiota may differ depending on the age group of patients with depression.

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Clozapine Treatment Is Associated With Higher Prescription Rate of Antipsychotic Monotherapy and Lower Prescription Rate of Other Concomitant Psychotropics: A Real-World Nationwide Study

Ochi S., Tagata H., Hasegawa N., Yasui-Furukori N., Iga J.I., Kashiwagi H., Kodaka F., Komatsu H., Tsuboi T., Tokutani A., Numata S., Ichihashi K., Onitsuka T., Muraoka H., Iida H., Ohi K., Atake K., Kishimoto T., Hori H., Takaesu Y., Takeshima M., Usami M., Makinodan M., Hashimoto N., Fujimoto M., Furihata R., Nagasawa T., Yamada H., Matsumoto J., Miura K., Kido M., Hishimoto A., Ueno S.I., Watanabe K., Inada K., Hashimoto R.

International Journal of Neuropsychopharmacology （International Journal of Neuropsychopharmacology） 25 （ 10 ） 818 - 826 2022年10月

ISSN 14611457

Background: Although clozapine is effective for treatment-resistant schizophrenia (TRS), the rate of clozapine prescription is still low. Whereas antipsychotic monotherapy is recommended in clinical practice guidelines, the rate of antipsychotic polypharmacy is still high. There is little evidence on whether a clozapine prescription influences changes in the rate of monotherapy and polypharmacy, including antipsychotics and other psychotropics. We therefore hypothesized that the rate of antipsychotic monotherapy in patients with TRS who were prescribed clozapine would be higher than that in patients with schizophrenia who were not prescribed clozapine. Methods: We assessed 8306 patients with schizophrenia nationwide from 178 institutions in Japan from 2016 to 2019. We analyzed the psychotropic prescription data at discharge in patients diagnosed with TRS and with no description of TRS (ND-TRS) based on the diagnosis listed in the discharge summary. Results: The rate of antipsychotic monotherapy in the TRS with clozapine group (91.3%) was significantly higher than that in the TRS without clozapine group (45.9%; P< 2.0 × 10−16) and the ND-TRS without clozapine group (54.7%; P< 2.0 × 10−16). The rate of antipsychotic monotherapy without any other concomitant psychotropics in the TRS with clozapine group (26.5%) was significantly higher than that in the TRS without clozapine group (12.6%; P= 1.1 × 10−6) and the ND-TRS without clozapine group (17.0%; P= 5.9 × 10−6). Conclusions: Clozapine prescription could be associated with a high rate of antipsychotic monotherapy. Patients will benefit from the correct diagnosis of TRS and thus from proper clozapine prescription.

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Effectiveness of electroconvulsive therapy in patients lacking decision making capacity: A systematic review and meta-analysis

Takamiya A., Sienaert P., Gergel T., Gather J., Kishimoto T., Zilles-Wegner D.

Brain Stimulation （Brain Stimulation） 15 （ 5 ） 1246 - 1253 2022年09月

ISSN 1935861X

Background: Electroconvulsive therapy (ECT) is provided for patients with severe and often life-threatening illness, who lack decision making capacity to consent to treatment (DMC-T) in clinical settings. Objective: The aim of this study is to summarize previous studies investigating clinical outcomes of ECT in patients lacking DMC-T. Methods: A systematic review and meta-analysis of studies reporting clinical outcomes of ECT in patients lacking DMC-T with any psychiatric diagnoses was conducted. The primary outcome was clinical improvement. Secondary outcomes were cognitive outcomes and six month readmission rate. Hedges’ g and odds ratios were calculated using a random-effects model. The protocol was registered in Open Science Framework (https://osf.io/rxjkm). Results: Of 3552 identified articles, 41 studies (n = 1299) were included. Approximately 80% of patients lacking DMC-T responded to ECT, and part of the patients regained capacity to consent and consented to further treatment with ECT. A total of seven studies (n = 1081) were included for meta-analysis. Patients without DMC-T showed superior clinical improvement and less cognitive side effects compared with those with DMC-T, whereas the groups did not show any difference in readmission rate. Several clinical characteristics at baseline and ECT techniques were significantly different between the groups. Conclusion: ECT is equally, if not superiorly, effective in patients lacking DMC-T compared to patients with DMC-T. ECT can potentially enhance patients’ autonomy, without increasing the risk of cognitive side effects. These results support the clinical and ethical legitimacy of ECT provision for patients with the most severe illness who lack DMC-T at start of treatment.

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Subjective assessment of participants in education programs on clinical practice guidelines in the field of psychiatry

Ogasawara K., Numata S., Hasegawa N., Nakataki M., Makinodan M., Ohi K., Takeshima M., Tsuboi T., Hashimoto N., Onitsuka T., Muraoka H., Hori H., Ichihashi K., Inagaki T., Yasui-Furukori N., Hishimoto A., Sugiyama N., Fukumoto K., Nagasawa T., Matsumoto J., Takaesu Y., Furihata R., Nemoto K., Nakamura T., Usami M., Miura K., Fujimoto M., Tagata H., Yamada H., Komatsu H., Ochi S., Atake K., Katsumoto E., Kido M., Kishimoto T., Suwa T., Yamamura S., Iga J.i., Iida H., Inada K., Watanabe K., Hashimoto R.

Neuropsychopharmacology Reports （Neuropsychopharmacology Reports） 42 （ 2 ） 221 - 225 2022年06月

The Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment (EGUIDE) project, which is a nationwide dissemination and implementation program for clinical practice guidelines (CPGs) in the field of psychiatry, is currently ongoing. In the current study, a subjective assessment of the participants in the EGUIDE programs was assessed using a questionnaire. Then, the relationships between the subjective assessment, the characteristics of the participants, and the clinical knowledge of the CPGs were evaluated. More than 90% of the participants gave a high rating for the components of content, recommendation, knowledge, skill, and adherence, but not for the component of confidence. A positive correlation was found between years of professional experience and the score of confidence. These results suggest that it may be necessary to apply the knowledge and skills of CPGs obtained in the education programs into practice to increase confidence in the proper use of psychiatric therapies based on CPGs.

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A dissemination and education programme to improve the clinical behaviours of psychiatrists in accordance with treatment guidelines for schizophrenia and major depressive disorders: the Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE) project

Yamada H., Motoyama M., Hasegawa N., Miura K., Matsumoto J., Ohi K., Yasui-Furukori N., Numata S., Takeshima M., Sugiyama N., Nagasawa T., Kubota C., Atake K., Tsuboi T., Ichihashi K., Hashimoto N., Inagaki T., Takaesu Y., Iga J.I., Hori H., Onitsuka T., Komatsu H., Hishimoto A., Fukumoto K., Fujimoto M., Nakamura T., Nemoto K., Furihata R., Yamamura S., Yamagata H., Ogasawara K., Katsumoto E., Murata A., Iida H., Ochi S., Makinodan M., Kido M., Kishimoto T., Yasuda Y., Usami M., Suwa T., Inada K., Watanabe K., Hashimoto R.

BJPsych Open （BJPsych Open） 8 （ 3 ） e83 2022年05月

ISSN 2056-4724

Background Clinical practice guidelines for schizophrenia and major depressive disorder have been published. However, these have not had sufficient penetration in clinical settings. We developed the Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE) project as a dissemination and education programme for psychiatrists. Aims The aim of this study is to assess the effectiveness of the EGUIDE project on the subjective clinical behaviour of psychiatrists in accordance with clinical practice guidelines before and 1 and 2 years after participation in the programmes. Method A total of 607 psychiatrists participated in this study during October 2016 and March 2019. They attended both 1-day educational programmes based on the clinical practice guidelines for schizophrenia and major depressive disorder, and answered web questionnaires about their clinical behaviours before and 1 and 2 years after attending the programmes. We evaluated the changes in clinical behaviours in accordance with the clinical practice guidelines between before and 2 years after the programme. Results All of the scores for clinical behaviours in accordance with clinical practice guidelines were significantly improved after 1 and 2 years compared with before attending the programmes. There were no significant changes in any of the scores between 1 and 2 years after attending. Conclusions All clinical behaviours in accordance with clinical practice guidelines improved after attending the EGUIDE programme, and were maintained for at least 2 years. The EGUIDE project could contribute to improved guideline-based clinical behaviour among psychiatrists.

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Characteristics of single-channel electroencephalogram in depression during conversation with noise reduction technology

Mitsukura Y., Tazawa Y., Nakamura R., Sumali B., Nakagawa T., Hori S., Mimura M., Kishimoto T.

PLoS ONE （PLoS ONE） 17 （ 4 April ） e0266518 2022年04月

ISSN 1932-6203

Background Previous studies have attempted to characterize depression using electroencephalography (EEG), but results have been inconsistent. New noise reduction technology allows EEG acquisition during conversation. Methods We recorded EEG from 40 patients with depression as they engaged in conversation using a single-channel EEG device while conducting real-time noise reduction and compared them to those of 40 healthy subjects. Differences in EEG between patients and controls, as well as differences in patients’ depression severity, were examined using the ratio of the power spectrum at each frequency. In addition, the effects of medications were examined in a similar way. Results In comparing healthy controls and depression patients, significant power spectrum differences were observed at 3 Hz, 4 Hz, and 10 Hz and higher frequencies. In the patient group, differences in the power spectrum were observed between asymptomatic patients and healthy individuals, and between patients of each respective severity level and healthy individuals. In addition, significant differences were observed at multiple frequencies when comparing patients who did and did not take antidepressants, antipsychotics, and/or benzodiazepines. However, the power spectra still remained significantly different between non-medicated patients and healthy individuals. Limitations The small sample size may have caused Type II error. Patients’ demographic characteristics varied. Moreover, most patients were taking various medications, and cannot be compared to the non-medicated control group. Conclusion A study with a larger sample size should be conducted to gauge reproducibility, but the methods used in this study could be useful in clinical practice as a biomarker of depression.

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特集 AI時代の医師のクリニカル・スキル-君は生き延びることができるか? 【Ⅰ章】AIの特性と能力 ❸10年後のAIはどこまで「診断」できるようになるか?

古川渉太, 木下翔太郎, 岸本泰士郎

総合診療（株式会社医学書院） 32 （ 3 ） 303 - 307 2022年03月

ISSN 21888051

The characteristics of patients receiving psychotropic pro re nata medication at discharge for the treatment of schizophrenia and major depressive disorder: A nationwide survey from the EGUIDE project

Ichihashi K., Kyou Y., Hasegawa N., Yasui-Furukori N., Shimizu Y., Hori H., Hashimoto N., Ide K., Imamura Y., Yamada H., Ochi S., Iga J.i., Takaesu Y., Ohi K., Tsuboi T., Iida H., Yamagata H., Hishimoto A., Horai T., Usami M., Makinodan M., Nagasawa T., Komatsu H., Kido M., Muraoka H., Atake K., Takeshima M., Kubota C., Inagaki T., Tamai S., Kishimoto T., Furihata R., Matsumoto J., Miura K., Inada K., Watanabe K., Kasai K., Hashimoto R.

Asian Journal of Psychiatry （Asian Journal of Psychiatry） 69 103007 2022年03月

ISSN 18762018

Background: Although several guidelines indicate that daily pharmacotherapy is an important part of the treatment of schizophrenia and major depressive disorder, there are few reports regarding pro re nata (PRN) prescriptions. The purpose of this study is to clarify the characteristics of patients receiving psychotropic PRN prescription for the treatment of schizophrenia and major depressive disorder. Method: We used data from ‘the effectiveness of guideline for dissemination and education in psychiatric treatment’ (EGUIDE) project to evaluate the presence or absence of psychotropic PRN prescription at the time of discharge, the age and sex of patients receiving PRN prescription for each diagnosis, and the association between PRN prescription and regular daily psychotropics. Results: The psychotropic PRN prescription ratio was 29.9% among 2617 patients with schizophrenia and 31.1% among 1248 patients with major depressive disorder at discharge. In schizophrenia, the psychotropic PRN prescription ratio was 21.6% for patients aged 65 years or older, which was lower than that of all other age groups. In major depressive disorder, the psychotropic PRN prescription ratio was 34.2% for female patients, which was significantly higher than that for male patients (25.5%). In schizophrenia, there was an association between psychotropic PRN prescription and regular use of multiple psychotropic medications. Conclusions: Psychotropic PRN prescription was less common in elderly patients with schizophrenia and more common in female patients with major depressive disorder. In schizophrenia, psychotropic PRN prescription led to polypharmacy of psychotropics. Further studies are needed to accumulate evidence and to provide education on appropriate PRN prescriptions.

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Physical and mental health impact of COVID-19 on children, adolescents, and their families: The Collaborative Outcomes study on Health and Functioning during Infection Times - Children and Adolescents (COH-FIT-C&A)

Solmi M., Estradé A., Thompson T., Agorastos A., Radua J., Cortese S., Dragioti E., Leisch F., Vancampfort D., Thygesen L.C., Aschauer H., Schloegelhofer M., Akimova E., Schneeberger A., Huber C.G., Hasler G., Conus P., Cuénod K.Q.D., von Känel R., Arrondo G., Fusar-Poli P., Gorwood P., Llorca P.M., Krebs M.O., Scanferla E., Kishimoto T., Rabbani G., Skonieczna-Żydecka K., Brambilla P., Favaro A., Takamiya A., Zoccante L., Colizzi M., Bourgin J., Kamiński K., Moghadasin M., Seedat S., Matthews E., Wells J., Vassilopoulou E., Gadelha A., Su K.P., Kwon J.S., Kim M., Lee T.Y., Papsuev O., Manková D., Boscutti A., Gerunda C., Saccon D., Righi E., Monaco F., Croatto G., Cereda G., Demurtas J., Brondino N., Veronese N., Enrico P., Politi P., Ciappolino V., Pfennig A., Bechdolf A., Meyer-Lindenberg A., Kahl K.G., Domschke K., Bauer M., Koutsouleris N., Winter S., Borgwardt S., Bitter I., Balazs J., Czobor P., Unoka Z., Mavridis D., Tsamakis K., Bozikas V.P., Tunvirachaisakul C., Maes M., Rungnirundorn T., Supasitthumrong T., Haque A., Brunoni A.R., Costardi C.G., Schuch F.B., Polanczyk G., Luiz J.M., Fonseca L., Aparicio L.V., Valvassori S.S., Nordentoft M., Vendsborg P., Hoffmann S.H., Sehli J., Sartorius N., Heuss S., Guinart D., Hamilton J., Kane J., Rubio J., Sand M.

Journal of Affective Disorders （Journal of Affective Disorders） 299 367 - 376 2022年02月

ISSN 01650327

Background: The COVID-19 pandemic has altered daily routines and family functioning, led to closing schools, and dramatically limited social interactions worldwide. Measuring its impact on mental health of vulnerable children and adolescents is crucial. Methods: The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT – www.coh-fit.com) is an on-line anonymous survey, available in 30 languages, involving >230 investigators from 49 countries supported by national/international professional associations. COH-FIT has thee waves (until the pandemic is declared over by the WHO, and 6–18 months plus 24–36 months after its end). In addition to adults, COH-FIT also includes adolescents (age 14–17 years), and children (age 6–13 years), recruited via non-probability/snowball and representative sampling and assessed via self-rating and parental rating. Non-modifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to promote health and prevent mental and physical illness in children and adolescents will be generated by COH-FIT. Co-primary outcomes are changes in well-being (WHO-5) and a composite psychopathology P-Score. Multiple behavioral, family, coping strategy and service utilization factors are also assessed, including functioning and quality of life. Results: Up to June 2021, over 13,000 children and adolescents from 59 countries have participated in the COH-FIT project, with representative samples from eleven countries. Limitations: Cross-sectional and anonymous design. Conclusions: Evidence generated by COH-FIT will provide an international estimate of the COVID-19 effect on children's, adolescents’ and families’, mental and physical health, well-being, functioning and quality of life, informing the formulation of present and future evidence-based interventions and policies to minimize adverse effects of the present and future pandemics on youth.

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The collaborative outcomes study on health and functioning during infection times in adults (COH-FIT-Adults): Design and methods of an international online survey targeting physical and mental health effects of the COVID-19 pandemic

Journal of Affective Disorders （Journal of Affective Disorders） 299 393 - 407 2022年02月

ISSN 01650327

Background:. High-quality comprehensive data on short-/long-term physical/mental health effects of the COVID-19 pandemic are needed. Methods:. The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is an international, multi-language (n=30) project involving >230 investigators from 49 countries/territories/regions, endorsed by national/international professional associations. COH-FIT is a multi-wave, on-line anonymous, cross-sectional survey [wave 1: 04/2020 until the end of the pandemic, 12 months waves 2/3 starting 6/24 months threreafter] for adults, adolescents (14-17), and children (6-13), utilizing non-probability/snowball and representative sampling. COH-FIT aims to identify non-modifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to improve social/health outcomes in the general population/vulnerable subgrous during/after COVID-19. In adults, co-primary outcomes are change from pre-COVID-19 to intra-COVID-19 in well-being (WHO-5) and a composite psychopathology P-Score. Key secondary outcomes are a P-extended score, global mental and physical health. Secondary outcomes include health-service utilization/functioning, treatment adherence, functioning, symptoms/behaviors/emotions, substance use, violence, among others. Results:. Starting 04/26/2020, up to 14/07/2021 >151,000 people from 155 countries/territories/regions and six continents have participated. Representative samples of ≥1,000 adults have been collected in 15 countries. Overall, 43.0% had prior physical disorders, 16.3% had prior mental disorders, 26.5% were health care workers, 8.2% were aged ≥65 years, 19.3% were exposed to someone infected with COVID-19, 76.1% had been in quarantine, and 2.1% had been COVID 19-positive. Limitations:. Cross-sectional survey, preponderance of non-representative participants. Conclusions:. Results from COH-FIT will comprehensively quantify the impact of COVID-19, seeking to identify high-risk groups in need for acute and long-term intervention, and inform evidence-based health policies/strategies during this/future pandemics.

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特集精神科におけるオンライン診療特集にあたって

岸本泰士郎

精神医学（株式会社医学書院） 64 （ 2 ） 125 - 125 2022年02月

ISSN 04881281

特集精神科におけるオンライン診療遠隔医療に関連した諸外国の政策動向

木下翔太郎, 岸本泰士郎

精神医学（株式会社医学書院） 64 （ 2 ） 137 - 145 2022年02月

ISSN 04881281

特集精神科におけるオンライン診療精神科におけるオンライン診療のエビデンス

岸本泰士郎, 木下翔太郎

精神医学（株式会社医学書院） 64 （ 2 ） 147 - 155 2022年02月

ISSN 04881281

特集オンライン診療への取り組みと今後の展望日本におけるオンライン診療の展開

岸本泰士郎, 木下翔太郎

整形・災害外科（金原出版） 65 （ 1 ） 33 - 39 2022年01月

ISSN 03874095

特集オンライン診療への取り組みと今後の展望精神科領域におけるオンライン診療への取り組み

木下翔太郎, 岸本泰士郎

整形・災害外科（金原出版） 65 （ 1 ） 41 - 47 2022年01月

ISSN 03874095

オンライン診療の適正な普及に関するヒアリング調査　現状把握と課題分析

木下翔太郎, 成瀬浩史, 吉村健佑, 岸本泰士郎, 榎戸芙佐子, 押淵英弘, 兼子幸一, 瀬戸秀文, 辻本哲士, 長尾喜一郎, 三野進, 村田昌彦, 米田博, 稲垣中

精神神経学雑誌（(公社)日本精神神経学会） 124 （ 1 ） 16 - 27 2022年01月

ISSN 0033-2658

2020年から始まった新型コロナウイルス感染症の拡大のなかで,感染予防策の1つとして,遠隔医療が注目されることとなり,世界各国で規制緩和が行われ利用が促進された.わが国でも,種々の規制緩和により,従来利用が少なかった精神科領域でもオンライン診療が活用されることが増えた.日本精神神経学会オンライン精神科医療検討作業班では,オンライン診療の現状把握と課題分析を目的として,臨床現場でオンライン診療の実践に取り組む医療機関にヒアリング調査を行った.17の医療機関から調査の協力を得られた.回答した医療機関のうち6施設(35.3%)が2020年から新たにオンライン診療を導入しており,15施設(88.2%)で新型コロナウイルス感染症の拡大における時限的・特例的な措置に基づく診療を行っており,今般の規制緩和によって利用が拡大していることが示唆された.また,導入に際しての困難については,7施設(41.2%)が診療報酬の価格の低さや対象範囲の狭さを挙げており,精神科診療でオンライン診療を普及させるうえでの課題についての質問でも,診療報酬の価格を対面診療に近づけることと回答した医療機関が9施設(52.9%)であり,診療報酬が普及の障害となっていると考える医療機関が多かった.厚生労働省に対する要望についての質問でも,診療報酬の点数や施設基準の改善を求めるという回答が12施設(70.6%)と圧倒的に多かった.オンライン診療は患者のニーズに合わせた普及がなされるべきであり,普及の障害となっている規制で合理性に欠けるものについては,見直しがされていくことが望ましいといえる.一方で,オンライン診療の安易な多用は,医療の質の観点から問題となる場合もあると考えられるため,適切な規制のあり方についての議論も継続していくべきである.(著者抄録)

Association of work environment with stress and depression among Japanese workers

Shiga K., Izumi K., Minato K., Yoshimura M., Kitazawa M., Hanashiro S., Cortright K., Kurokawa S., Momota Y., Sado M., Maeno T., Takebayashi T., Mimura M., Kishimoto T.

Work （Work） 72 （ 4 ） 1321 - 1335 2022年

ISSN 10519815

BACKGROUND: There is a lack of studies that investigated the effect of a wide range of work environmental factors on stress and depression in Japan. OBJECTIVES: To examine the association of work environment factors with stress and depression among workers in Japan. METHODS: We conducted questionnaire surveys of workers that mainly engage in desk work in Japan. Stress was assessed through the Perceived Stress Scale (PSS), depression through the Patient Health Questionnaire-9 (PHQ-9), and work environment through physical and psychological workplace environment questionnaires. Workers were divided into low and high stress groups based on PSS score (median split), and divided into non-depressed and depressed groups based on their PHQ-9 score (< 5, and ≥5); these groups were then compared with their working environment. In addition, a multiple regression analysis was performed. RESULTS: Responses were obtained from 210 subjects. Multiple regression analysis showed that 'Ability to work at one's own pace' and 'Ability to apply personal viewpoint to work,' etc., had effect on stress, while 'Workplace harassment' and 'Support from colleagues,' etc., had effect on depression. CONCLUSIONS: The results suggest that stress and depression in Japanese workers are related to factors such as job demands, control of work, workplace harassment, and psychological safety.

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大規模ツイートデータを用いたメンタルヘルス不調者の推測

高須遼, 中村啓信, 岸本泰士郎, 狩野芳伸

人工知能学会全国大会論文集（一般社団法人人工知能学会） JSAI2022 （ 0 ） 1J4OS13a04 - 1J4OS13a04 2022年

メンタルヘルスは社会的に重要な問題である。近年、メンタルヘルスの問題はインターネット上の活動と密接に関係している。そこで我々は、Twitterユーザーがメンタルヘルス問題を抱えているかどうかを分類するシステムを開発した。特定のパターンに合致するアカウントはメンタルヘルス問題を抱えている可能性が高いと仮定し、この仮定に基づいてポジティブな例とネガティブな例を100万件規模で収集した。また、キーワードに依存する先行研究とは異なり、メンタルヘルスに特化したキーワードを含まないユーザの発話を分類する可能性を検討するため、そのようなキーワードを含むツイートはデータセットから排除した。BERT、LSTM、SVMを学習させ、分類性能を比較した。BERTについては、大規模ツイートデータを用いた事前学習を行った。BERTが最も高い性能を示し、Accuracy 0.83, Recall 0.8, Precision 0.88,F1-score 0.84という実用レベルの高い分類性能を達成した。文脈情報の重要性とともに、一般的な発話からメンタルヘルス不調を推測しうることを示した。

Current Status and Challenges of the Dissemination of Telemedicine in Japan After the Start of the COVID-19 Pandemic

Kinoshita Shotaro, Kishimoto Taishiro

TELEMEDICINE AND E-HEALTH （Telemedicine and e-Health） 28 （ 8 ） 1220 - 1224 2021年12月

ISSN 1530-5627

Background: The use of telemedicine is expanding worldwide in response to the COVID-19 pandemic, and deregulation is occurring even in countries with strict regulations, such as Japan. Methods: We conducted a narrative review of the activities and initiatives undertaken by the government and professional organizations to promote the use of telemedicine in Japan from January 2020, when the COVID-19 pandemic began, to September 2021. Results: In Japan, where before the pandemic the spread of telemedicine had been limited, various recommendations and deregulations have now been made, resulting in the expanded use of telemedicine. In particular, the government's overall policy direction has become a catalyst for deregulation. Conclusions: With the COVID-19 pandemic, telemedicine is now moving toward widespread use. However, further activities and initiatives, including policy changes such as reimbursement and the establishment of evidence to show the effectiveness of telemedicine in Japan, are needed to properly disseminate telemedicine.

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Japanese project for telepsychiatry evaluation during COVID-19: Treatment comparison trial (J-PROTECT): Rationale, design, and methodology

Kishimoto T., Kinoshita S., Bun S., Sato Y., Kitazawa M., Kikuchi T., Sado M., Takamiya A., Mimura M., Nakamae T., Abe Y., Kanazawa T., Kawabata Y., Tomita H., Abe K., Hishimoto A., Asami T., Suda A., Watanabe Y., Amagai T., Sakuma K., Kida H., Funayama M., Kimura H., Sato A., Fujiwara S., Nagao K., Sugiyama N., Takamiya M., Kodama H., Azekawa T.

Contemporary Clinical Trials （Contemporary Clinical Trials） 111 106596 2021年12月

ISSN 15517144

Introduction: The COVID-19 pandemic has had a profound impact on the mental health of people around the world. Anxiety related to infection, stress and stigma caused by the forced changes in daily life have reportedly increased the incidence and symptoms of depression, anxiety disorder and obsessive-compulsive disorder. Under such circumstances, telepsychiatry is gaining importance and attracting a great deal of attention. However, few large pragmatic clinical trials on the use of telepsychiatry targeting multiple psychiatric disorders have been conducted to date. Methods: The targeted study cohort will consist of adults (>18 years) who meet the DSM-5 diagnostic criteria for either (1) depressive disorders, (2) anxiety disorders, or (3) obsessive-compulsive and related disorders. Patients will be assigned in a 1:1 ratio to either a “telepsychiatry group” (at least 50% of treatments to be conducted using telemedicine, with at least one face-to-face treatment [FTF] within six months) or an “FTF group” (all treatments to be conducted FTF, with no telemedicine). Both groups will receive the usual treatment covered by public medical insurance. The study will utilize a master protocol design in that there will be primary and secondary outcomes for the entire group regardless of diagnosis, as well as the outcomes for each individual disorder group. Discussion: This study will be a non-inferiority trial to test that the treatment effect of telepsychiatry is not inferior to that of FTF alone. This study will provide useful insights into the effect of the COVID-19 pandemic on the practice of psychiatry. Trial Registration: jRCT1030210037, Japan Registry of Clinical Trials (jRCT).

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Response to Morina et al.'s criticisms of Horigome et al.'s recent report on the efficacy of virtual reality exposure therapy for social anxiety disorder.

Horigome T, Kurokawa S, Sawada K, Kudo S, Shiga K, Mimura M, Kishimoto T

Psychological medicine 1 - 2 2021年10月

ISSN 0033-2917

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Neural Substrates of Psychotic Depression: Findings From the Global ECT-MRI Research Collaboration.

Takamiya A, Dols A, Emsell L, Abbott C, Yrondi A, Soriano Mas C, Jorgensen MB, Nordanskog P, Rhebergen D, van Exel E, Oudega ML, Bouckaert F, Vandenbulcke M, Sienaert P, Péran P, Cano M, Cardoner N, Jorgensen A, Paulson OB, Hamilton P, Kampe R, Bruin W, Bartsch H, Ousdal OT, Kessler U, van Wingen G, Oltedal L, Kishimoto T

Schizophrenia bulletin （Schizophrenia Bulletin） 48 （ 2 ） 514 - 523 2021年10月

ISSN 0586-7614

Psychotic major depression (PMD) is hypothesized to be a distinct clinical entity from nonpsychotic major depression (NPMD). However, neurobiological evidence supporting this notion is scarce. The aim of this study is to identify gray matter volume (GMV) differences between PMD and NPMD and their longitudinal change following electroconvulsive therapy (ECT). Structural magnetic resonance imaging (MRI) data from 8 independent sites in the Global ECT-MRI Research Collaboration (GEMRIC) database (n = 108; 56 PMD and 52 NPMD; mean age 71.7 in PMD and 70.2 in NPMD) were analyzed. All participants underwent MRI before and after ECT. First, cross-sectional whole-brain voxel-wise GMV comparisons between PMD and NPMD were conducted at both time points. Second, in a flexible factorial model, a main effect of time and a group-by-time interaction were examined to identify longitudinal effects of ECT on GMV and longitudinal differential effects of ECT between PMD and NPMD, respectively. Compared with NPMD, PMD showed lower GMV in the prefrontal, temporal and parietal cortex before ECT; PMD showed lower GMV in the medial prefrontal cortex (MPFC) after ECT. Although there was a significant main effect of time on GMV in several brain regions in both PMD and NPMD, there was no significant group-by-time interaction. Lower GMV in the MPFC was consistently identified in PMD, suggesting this may be a trait-like neural substrate of PMD. Longitudinal effect of ECT on GMV may not explain superior ECT response in PMD, and further investigation is needed.

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特集オンライン診療・医療AI最前線オンライン診療・医療AIを取り巻く環境　海外における遠隔医療・医療AIの動静と現状

木下翔太郎, 飯塚真理, 岸本泰士郎

診断と治療（(株)診断と治療社） 109 （ 9 ） 1219 - 1224 2021年09月

ISSN 0370999X

Gastrointestinal symptoms and sensory abnormalities associated with behavioral problems in children with neurodevelopmental disorders

Kurokawa S., Nomura K., Miyaho K., Sanada K., Iwamoto C., Naraoka M., Yoneda S., Tomizawa Y., Sawae Y., Iwanaga R., Mimura M., Kishimoto T.

Autism Research （Autism Research） 14 （ 9 ） 1996 - 2001 2021年09月

ISSN 19393792

Behavioral problems directly affect the quality of life of caregivers and children with autism spectrum disorder (ASD) and/or attention-deficit/hyperactivity disorder (ADHD), and is known to be associated with clinical factors such as gastrointestinal (GI) symptoms, sensory abnormalities, intellectual abilities, and use of medication. However, previous studies have not considered these relationships comprehensively. We conducted a cross-sectional study of 6–12-year-old children with diagnoses of ASD and/or ADHD at two hospitals in Japan. Scores for the aberrant behavior checklist (ABC), autism-spectrum quotient (AQ), and Conners 3, as well as information on daily sleep and exercise, GI symptoms, and Short Sensory Profile, were collected. Each factor was subjected to a correlation analysis to investigate its effect on ABC scores. A stepwise multiple linear regression analysis for the factors with p < 0.05 was performed. Data were obtained from 60 patients with a mean age of 8.3 years; 21 had ASD alone, 18 had ADHD alone, and 21 had ASD + ADHD. The correlation analyses identified six factors associated with ABC severity: (a) methylphenidate use, (b) Conners hyperactivity score, (c) Conners inattention score, (d) AQ score, (e) SSP score, and (f) GI symptom score. The multiple regression showed that “GI symptoms” and “sensory abnormalities” were independently associated with ABC severity. Although further studies are needed to show a causal relationship, appropriate assessment of GI symptoms and sensory abnormalities may help alleviate some problematic behaviors and improve the quality of life of children with neurodevelopmental disorders and their families. Lay summary: Behavioral problems in children with neurodevelopmental disorders are known to be associated with many factors. This study aimed to comprehensively investigate the known factors. We have discovered that “gastrointestinal symptoms” and “sensory abnormalities” were independently associated with Behavioral problems. Our results suggest that it is important for clinicians and caregivers to pay more attention to children's GI symptoms and sensory abnormalities that may not present as obvious symptoms or complaints.

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Electroconvulsive Therapy for Patients with Depression Who Lack Capacity for Consent: Doing Good and Doing No Harm

Takamiya A., Bouckaert F., Sienaert P., Uchida T., Kudo S., Yamagata B., Kishimoto T., Mimura M., Hirano J.

Journal of ECT （Journal of ECT） 37 （ 3 ） 171 - 175 2021年09月

ISSN 10950680

Objective Electroconvulsive therapy (ECT) is provided in real-world clinical settings for patients lacking capacity for consent. The aim of this study was to investigate the clinical characteristics and clinical effectiveness of ECT in this population. Methods A retrospective chart review was conducted to collect data from patients who received ECT to treat their depressive episodes between April 2012 and March 2019. Differences in clinical characteristics and short-/long-term clinical outcomes between patients who received ECT with their relatives' consent and patients who received ECT by their own consent were examined. The short-/long-term clinical outcomes were determined by clinical global impression scores and readmission rate, respectively. Results Of 168 patients with depressive episodes, 34 (20.2%) received ECT with their relatives' consent. Those patients were older, had lower body mass index, and had shorter episode duration. They also exhibited more frequent psychotic, melancholic, and catatonic features. The main indication for ECT in this population was the need for rapid recovery. Patients lacking capacity for consent showed similar remission (61.8%) and response (82.4%) rates to those with capacity for consent. Readmission rate was not significantly different between groups. Conclusions There were no significant differences in short-/long-term ECT effectiveness between patients with/without capacity for consent. Electroconvulsive therapy is the only established and effective treatment in clinical settings for the most severe cases, wherein patients are incapable of giving consent but need rapid recovery. A general rejection of this practice due to concerns surrounding consent may be unethical under the ethical principles of medical care.

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Subjective well-being and month-long LF/HF ratio among deskworkers

Shiga K., Izumi K., Minato K., Sugio T., Yoshimura M., Kitazawa M., Hanashiro S., Cortright K., Kurokawa S., Momota Y., Sado M., Maeno T., Takebayashi T., Mimura M., Kishimoto T.

PLoS ONE （PLoS ONE） 16 （ 9 September ） e0257062 2021年09月

ISSN 1932-6203

The importance of workers' well-being has been recognized in recent years. The assessment of well-being has been subjective, and few studies have sought potential biomarkers of well-being to date. This study examined the relationship between well-being and the LF/HF ratio, an index of heart rate variability that reflects sympathetic and parasympathetic nerve activity. Pulse waves were measured using photoplethysmography through a web camera attached to the computer used by each participant. The participants were asked to measure their pulse waves while working for 4 weeks, and well-being was assessed using self-reported measures such as the Satisfaction With Life Scale (SWLS), the Positive and Negative Affect Schedule (PANAS), and the Flourishing Scale (FS). Each of the well-being scores were split into two groups according to the median value, and the LF/HF ratio during work, as well as the number of times an LF/HF ratio threshold was either exceeded or subceeded, were compared between the high and low SWLS, positive emotion, negative emotion, and FS groups. Furthermore, to examine the effects of the LF/HF ratio and demographic characteristics on well-being, a multiple regression analysis was conducted. Data were obtained from 169 participants. The results showed that the low FS group had a higher mean LF/HF ratio during work than the high FS group. No significant differences were seen between the high and low SWLS groups, the high and low positive emotion groups, or the high and low negative emotion groups. The multiple regression analysis showed that the mean LF/HF ratio during work affected the FS and SWLS scores, and the number of times the mean LF/HF ratio exceeded +3 SD had an effect on the positive emotion. No effect of the LF/HF ratio on negative emotions was shown. The LF/HF ratio might be applicable as an objective measure of well-being.

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Association of electroconvulsive therapy-induced structural plasticity with clinical remission

Takamiya A., Kishimoto T., Hirano J., Kikuchi T., Yamagata B., Mimura M.

Progress in Neuro-Psychopharmacology and Biological Psychiatry （Progress in Neuro-Psychopharmacology and Biological Psychiatry） 110 110286 2021年08月

ISSN 02785846

© 2021 Elsevier Inc. Background: Electroconvulsive therapy (ECT) is the most effective treatment for severe depression. Recent neuroimaging studies have consistently reported that ECT induces volume increases in widely distributed brain regions. However, it still remains unclear about ECT-induced volume changes associated with clinical improvement. Methods: Longitudinal assessments of structural magnetic resonance imaging were conducted in 48 participants. Twenty-seven elderly melancholic depressed individuals (mean 67.5 ± 8.1 years old; 19 female) were scanned before (TP1) and after (TP2) ECT. Twenty-one healthy controls were also scanned twice. Whole-brain gray matter volume (GMV) was analyzed via group (remitters, nonremitters, and controls) by time (TP1 and TP2) analysis of covariance to identify ECT-related GMV changes and GMV changes specific to remitters. Within-subject and between-subjects correlation analyses were conducted to investigate the associations between clinical improvement and GMV changes. Depressive symptoms were evaluated using the 17-item Hamilton Depression Rating Scale (HAM-D), and remission was defined as HAM-D total score ≤ 7. Results: Bilateral ECT increased GMV in multiple brain regions bilaterally regardless of clinical improvement. Remitters showed a larger GMV increase in the right-lateralized frontolimbic brain regions compared to nonremitters and healthy controls. GMV changes in the right hippocampus/amygdala and right middle frontal gyrus showed correlations with clinical improvement in within−/between-subjects correlation analyses. Conclusions: ECT-induced GMV increase in the right frontolimbic regions was associated with clinical remission.

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Fecal Microbial and Metabolomic Change during treatment course for depression: An Observational Study

Kurokawa S., Tomizawa Y., Miyaho K., Ishii D., Takamiya A., Ishii C., Sanada K., Fukuda S., Mimura M., Kishimoto T.

Journal of Psychiatric Research （Journal of Psychiatric Research） 140 45 - 52 2021年08月

ISSN 00223956

Background: There is growing evidence regarding the connection between alterations in gut microbiota and their metabolites in patients with depressive disorders, suggesting a potential role in pathophysiology. Our study aimed to investigate the relationship between microbial, metabolomic features and the course of treatment for depression in a real-world clinical setting. Methods: Patients diagnosed with depressive disorders were recruited, and their stool was collected at three time points during their depression treatments. Patients were divided into three groups: non-responders, responders, and stable remitters. Gut microbiomes were analyzed using 16S rRNA gene sequencing, and gut metabolomes were analyzed by a mass spectrometry approach. Microbiomes/metabolomes were compared between groups cross-sectionally and longitudinally. Results: A total of 33 patients were recruited and divided into non-responders (n = 16), responders (n = 11), and stable remitters (n = 6). Non-responders presented lower alpha diversity in the Phylogenic Diversity index compared to responders during the treatment course (p = 0.003). Non-responders presented increased estimated glutamate synthesis functions by the microbiota compared to responders and stable remitters (p = 0.035). There were no specific microbiota or metabolome that differentiated the three groups. Limitations: Small sample size with no healthy controls. Conclusions: Our results indicate that both cross-sectional microbial features and longitudinal microbial transitions are different depending on the treatment course of depression. Controlled studies, as well as animal studies, are needed in the future to elucidate the causal relationship between microbiota and depression.

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Long-acting injectable versus oral antipsychotics for schizophrenia reply

Kishimoto Taishiro, Hagi Katsuhiko, Kurokawa Shunya, Kane John M., Correll Christoph U.

LANCET PSYCHIATRY 8 （ 7 ） 567 - 567 2021年07月

ISSN 2215-0374

Elevated body weight modulates subcortical volume change and associated clinical response following electroconvulsive therapy

Opel N., Narr K.L., Abbott C., Argyelan M., Espinoza R., Emsell L., Bouckaert F., Sienaert P., Vandenbulcke M., Nordanskog P., Repple J., Kavakbasi E., Jorgensen M.B., Paulson O.B., Hanson L.G., Dols A., Van Exel E., Oudega M.L., Takamiya A., Kishimoto T., Ousdal O.T., Haavik J., Hammar Å., Oedegaard K.J., Kessler U., Bartsch H., Dale A.M., Baune B.T., Dannlowski U., Oltedal L., Redlich R.

Journal of Psychiatry and Neuroscience （Journal of Psychiatry and Neuroscience） 46 （ 4 ） E418 - E426 2021年07月

ISSN 11804882

Background: Obesity is a frequent somatic comorbidity of major depression, and it has been associated with worse clinical outcomes and brain structural abnormalities. Converging evidence suggests that electroconvulsive therapy (ECT) induces both clinical improvements and increased subcortical grey matter volume in patients with depression. However, it remains unknown whether increased body weight modulates the clinical response and structural neuroplasticity that occur with ECT. Methods: To address this question, we conducted a longitudinal investigation of structural MRI data from the Global ECT-MRI Research Collaboration (GEMRIC) in 223 patients who were experiencing a major depressive episode (10 scanning sites). Structural MRI data were acquired before and after ECT, and we assessed change in subcortical grey matter volume using FreeSurfer and Quarc. Results: Higher body mass index (BMI) was associated with a significantly lower increase in subcortical grey matter volume following ECT. We observed significant negative associations between BMI and change in subcortical grey matter volume, with pronounced effects in the thalamus and putamen, where obese participants showed increases in grey matter volume that were 43.3% and 49.6%, respectively, of the increases found in participants with normal weight. As well, BMI significantly moderated the association between subcortical grey matter volume change and clinical response to ECT. We observed no significant association between BMI and clinical response to ECT. Limitations: Because only baseline BMI values were available, we were unable to study BMI changes during ECT and their potential association with clinical and grey matter volume change. Conclusion: Future studies should take into account the relevance of body weight as a modulator of structural neuroplasticity during ECT treatment and aim to further explore the functional relevance of this novel finding.

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Associations Between Gut Microbiota and Treatment Response in Patients With Major Depressive Disorders Stratified by Dairy Intake: A Prospective Observational Study

Tachibana Tomoyuki, Sanada Kenji, Miyaho Katsuma, Kurokawa Shunya, Nakajima Shinichiro, Kishimoto Taishiro, Iwanami Akira

BIOLOGICAL PSYCHIATRY 89 （ 9 ） S228 - S229 2021年05月

ISSN 0006-3223

The Potential Impact of Age on the Gut Microbiota in Patients With Major Depressive Disorders: A Prospective Observational Study

Miyaho Katsuma, Sanada Kenji, Kurokawa Shunya, Tanaka Arisa, Noda Yoshihiro, Nakajima Shinichiro, Kishimoto Taishiro, Iwanami Akira

BIOLOGICAL PSYCHIATRY 89 （ 9 ） S341 - S341 2021年05月

ISSN 0006-3223

Long-acting injectable versus oral antipsychotics for the maintenance treatment of schizophrenia: a systematic review and comparative meta-analysis of randomised, cohort, and pre–post studies

Kishimoto T., Hagi K., Kurokawa S., Kane J.M., Correll C.U.

The Lancet Psychiatry （The Lancet Psychiatry） 8 （ 5 ） 387 - 404 2021年05月

ISSN 22150366

Background: Evidence of comparative benefits of long-acting injectable antipsychotics (LAIs) versus oral antipsychotics for schizophrenia has been inconsistent across study designs. The aim of this study was to evaluate the comparative benefits of LAIs versus oral antipsychotics in three study designs to inform clinical decision making. Methods: We did a comprehensive systematic review and meta-analysis comparing LAIs versus oral antipsychotics for schizophrenia covering three study designs: randomised controlled trials (RCTs), cohort studies, and pre–post studies. Our literature search was without language restrictions, in MEDLINE and PubMed, the Cochrane Library, Scopus, and Embase, for studies published from database inception up to a last search on March 13, 2020. We also searched for unpublished studies and ClinicalTrials.gov. We included studies lasting at least 6 months that targeted adults with schizophrenia and related disorders (>80% of participants). Studies on penfluridol (neither an LAI or daily oral antipsychotic), case reports, and case series with fewer than 20 patients were excluded. Two investigators independently extracted study-level data and resolved disagreement by consensus, or via a third investigator. Study authors were contacted to obtain additional information as needed. For our primary outcome we meta-analysed the risk ratio (RR) for hospitalisation or relapse with LAIs versus oral antipsychotics by a random-effects model, with hospitalisation used preferentially over relapse. As secondary analyses, we reversed the preferential order to relapse over hospitalisation, and assessed hospitalisation risk and relapse risk individually. Other secondary outcomes included all meta-analysable data, classed by relevance to effectiveness, efficacy, safety, quality of life, cognitive function, and other outcomes, and analysed by study design. Dichotomous outcomes were expressed as pooled RR and continuous outcomes as standardised mean difference (SMD). The protocol is registered with PROSPERO (CRD42019142094). Findings: We identified 14 687 records, of which 137 studies (397 319 patients) met the inclusion criteria (32 RCTs [23·4%; 8577 patients], 65 cohort studies [47·4%; 377 447 patients], and 40 pre–post studies [29·2%; 11 295 patients]) and were analysed. The quality of studies in terms of risk of bias varied across study designs and within each study design from low to high. LAIs were associated with a lower risk of hospitalisation or relapse than oral antipsychotics in each of the three study designs (RCTs: 29 studies, 7833 patients, RR 0·88 [95% CI 0·79–0·99], p=0·033; cohort studies: 44 studies, 106 136 patients, RR 0·92 [0·88–0·98], p=0·0044; pre–post studies: 28 studies, 17 876 patients, RR 0·44 [0·39–0·51], p<0·0001). This association was maintained across the study designs when we reversed the preferential order to risk of relapse over hospitalisation, and in individual analysis of hospitalisation risk. The association was maintained only in pre–post studies for relapse risk alone. In all other outcomes related to effectiveness, efficacy, safety, quality of life, cognitive function, and other outcomes, LAIs were more beneficial than oral antipsychotics in 60 (18·3%) of 328 comparisons, not different in 252 (76·8%) comparisons, and less beneficial in 16 (4·9%) comparisons when analysed by study design. Significant heterogeneity was observed across all three study designs. Publication biases were apparent in cohort and pre-post studies, but effect sizes were similar after trim-and-fill analyses. Interpretation: Although study designs have strengths and weaknesses, including potential low quality of observational studies, we consistently identified significant benefit with LAIs versus oral antipsychotics in preventing hospitalisation or relapse, in settings ranging from restricted research (RCTs) to real-word application (cohort and pre–post studies). Our findings suggest that increased clinical use of LAIs could improve outcomes in schizophrenia. Funding: None. Translations: For the Chinese, French, German, Italian, Japanese, Portugese and Spanish translations of the abstract see Supplementary Materials section.

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Personalization of repetitive transcranial magnetic stimulation for the treatment of major depressive disorder according to the existing psychiatric comorbidity

Chou P.H., Lin Y.F., Lu M.K., Chang H.A., Chu C.S., Chang W.H., Kishimoto T., Sack A.T., Su K.P.

Clinical Psychopharmacology and Neuroscience （Clinical Psychopharmacology and Neuroscience） 19 （ 2 ） 190 - 205 2021年05月

ISSN 17381088

Repetitive transcranial magnetic stimulation (rTMS) and intermittent theta-burst stimulation (iTBS) are evidenced-based treatments for patients with major depressive disorder (MDD) who fail to respond to standard first-line therapies. However, although various TMS protocols have been proven to be clinically effective, the response rate varies across clinical applications due to the heterogeneity of real-world psychiatric comorbidities, such as generalized anxiety disorder, posttraumatic stress disorder, panic disorder, or substance use disorder, which are often observed in patients with MDD. Therefore, individualized treatment approaches are important to increase treatment response by assigning a given patient to the most optimal TMS treatment protocol based on his or her individual profile. This literature review summarizes different rTMS or TBS protocols that have been applied in researches investigating MDD patients with certain psychiatric comorbidities and discusses biomarkers that may be used to predict rTMS treatment response. Furthermore, we highlight the need for the validation of neuroimaging and electrophysiological biomarkers associated with rTMS treatment responses. Finally, we discuss on which directions future efforts should focus for developing the personalization of the treatment of depression with rTMS or iTBS.

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Unobtrusive Sensing Technology for Quantifying Stress and Well-Being Using Pulse, Speech, Body Motion, and Electrodermal Data in a Workplace Setting: Study Concept and Design

Izumi K., Minato K., Shiga K., Sugio T., Hanashiro S., Cortright K., Kudo S., Fujita T., Sado M., Maeno T., Takebayashi T., Mimura M., Kishimoto T.

Frontiers in Psychiatry （Frontiers in Psychiatry） 12 611243 2021年04月

ISSN 1664-0640

Introduction: Mental disorders are a leading cause of disability worldwide. Depression has a significant impact in the field of occupational health because it is particularly prevalent during working age. On the other hand, there are a growing number of studies on the relationship between “well-being” and employee productivity. To promote healthy and productive workplaces, this study aims to develop a technique to quantify stress and well-being in a way that does not disturb the workplace. Methods and analysis: This is a single-arm prospective observational study. The target population is adult (>20 years old) workers at companies that often engage in desk work; specifically, a person who sits in front of a computer for at least half their work hours. The following data will be collected: (a) participants' background characteristics; (b) participants' biological data during the 4-week observation period using sensing devices such as a camera built into the computer (pulse wave data extracted from the facial video images), a microphone built into their work computer (voice data), and a wristband-type wearable device (electrodermal activity data, body motion data, and body temperature); (c) stress, well-being, and depression rating scale assessment data. The analysis workflow is as follows: (1) primary analysis, comprised of using software to digitalize participants' vital information; (2) secondary analysis, comprised of examining the relationship between the quantified vital data from (1), stress, well-being, and depression; (3) tertiary analysis, comprised of generating machine learning algorithms to estimate stress, well-being, and degree of depression in relation to each set of vital data as well as multimodal vital data. Discussion: This study will evaluate digital phenotype regarding stress and well-being of white-collar workers over a 4-week period using persistently obtainable biomarkers such as heart rate, acoustic characteristics, body motion, and electrodermal activity. Eventually, this study will lead to the development of a machine learning algorithm to determine people's optimal levels of stress and well-being. Ethics and dissemination: Collected data and study results will be disseminated widely through conference presentations, journal publications, and/or mass media. The summarized results of our overall analysis will be supplied to participants. Registration: UMIN000036814

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Cognitive Intervention Through Photo-Integrated Conversation Moderated by Robots (PICMOR) Program: A Randomized Controlled Trial

Otake-Matsuura M., Tokunaga S., Watanabe K., Abe M.S., Sekiguchi T., Sugimoto H., Kishimoto T., Kudo T.

Frontiers in Robotics and AI （Frontiers in Robotics and AI） 8 633076 2021年04月

ISSN 2296-9144

Social interaction might prevent or delay dementia, but little is known about the specific effects of various social activity interventions on cognition. This study conducted a single-site randomized controlled trial (RCT) of Photo-Integrated Conversation Moderated by Robots (PICMOR), a group conversation intervention program for resilience against cognitive decline and dementia. In the RCT, PICMOR was compared to an unstructured group conversation condition. Sixty-five community-living older adults participated in this study. The intervention was provided once a week for 12 weeks. Primary outcome measures were the cognitive functions; process outcome measures included the linguistic characteristics of speech to estimate interaction quality. Baseline and post-intervention data were collected. PICMOR contains two key features: 1) photos taken by the participants are displayed and discussed sequentially; and 2) a robotic moderator manages turn-taking to make sure that participants are allocated the same amount of time. Among the primary outcome measures, one of the subcategories of cognitive functions, verbal fluency significantly improved in the intervention group. Among the process outcome measures, a part of the subcategories of linguistic characteristics of speech, the amount of speech and richness of words, proportion of providing topics, questions, and answers in total utterances were larger for the intervention group. This study demonstrated for the first time the positive effects of a robotic social activity intervention on cognitive function in healthy older adults via RCT. The group conversation generated by PICMOR may improve participants’ verbal fluency since participants have more opportunity to provide their own topics, asking and answering questions which results in exploring larger vocabularies. PICMOR is available and accessible to community-living older adults. Clinical Trial Registration: UMIN Clinical Trials Registry, identifier UMIN000036667.

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Improvements in the degree of understanding the treatment guidelines for schizophrenia and major depressive disorder in a nationwide dissemination and implementation study

Numata S., Nakataki M., Hasegawa N., Takaesu Y., Takeshima M., Onitsuka T., Nakamura T., Edagawa R., Edo H., Miura K., Matsumoto J., Yasui-Furukori N., Kishimoto T., Hori H., Tsuboi T., Yasuda Y., Furihata R., Muraoka H., Ochi S., Nagasawa T., Kyou Y., Murata A., Katsumoto E., Ohi K., Hishimoto A., Inada K., Watanabe K., Hashimoto R.

Neuropsychopharmacology Reports （Neuropsychopharmacology Reports） 41 （ 2 ） 199 - 206 2021年

© 2021 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Society of NeuropsychoPharmacology. Background: To implement clinical practice guidelines (CPGs), it is necessary for psychiatrists to deepen their understanding of the CPGs. The Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE) project is a nationwide dissemination and implementation study of two sets of CPGs for schizophrenia and major depressive disorder (MDD). Methods: A total of 413 psychiatrists (n = 212 in 2016; n = 201 in 2017) learned the two CPGs in the education program of the EGUIDE project, and clinical knowledge of these CPGs was evaluated at baseline and after the programs. To improve the correct answer rate for clinical knowledge after the programs, we revised the lecture materials associated with items that had a low correct answer rate in 2016 and used the revised lecture materials with the CPGs in 2017. The rates of correct answers after the programs between the 2016 and 2017 groups were compared. Results: The correct answer rate of one item on the schizophrenia CPG and one item on the MDD CPG tended to be improved (S-D5 and D-C6) and that of one on the MDD CPG was significantly improved (D-D3, P = 0.0008) in the 2017 group compared to those in the 2016 group. Conclusions: We reported improvements in clinical knowledge of CPGs after the EGUIDE program in the 2017 group following revision of the lecture materials based on results from the 2016 group. These attempts to improve the degree of understanding of CPGs may facilitate the successful dissemination and implementation of psychiatric guidelines in everyday practice.

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Speech paralinguistic approach for detecting dementia using gated convolutional neural network

Rodrigues Makiuchi M., Warnita T., Inoue N., Shinoda K., Yoshimura M., Kitazawa M., Funaki K., Eguchi Y., Kishimoto T.

IEICE Transactions on Information and Systems （IEICE Transactions on Information and Systems） 104 （ 11 ） 1930 - 1940 2021年

ISSN 09168532

We propose a non-invasive and cost-effective method to automatically detect dementia by utilizing solely speech audio data. We extract paralinguistic features for a short speech segment and use Gated Convolutional Neural Networks (GCNN) to classify it into dementia or healthy. We evaluate our method on the Pitt Corpus and on our own dataset, the PROMPT Database. Our method yields the accuracy of 73.1% on the Pitt Corpus using an average of 114 seconds of speech data. In the PROMPT Database, our method yields the accuracy of 74.7% using 4 seconds of speech data and it improves to 80.8% when we use all the patient’s speech data. Furthermore, we evaluate our method on a three-class classification problem in which we included the Mild Cognitive Impairment (MCI) class and achieved the accuracy of 60.6% with 40 seconds of speech data.

ビデオ会議システムを用いて高齢者に行う神経心理検査:—信頼性と実施上の留意点

飯干紀代子, 山岡義尚, 江口洋子, 加藤佑佳, 成本迅, 吉田和生, 岸本泰士郎, 三村將

認知神経科学（認知神経科学会） 22 （ 3 ） 158 - 167 2021年

ISSN 1344-4298

【要旨】社会の高齢化に伴い、認知症をはじめとして高齢者に神経心理検査を行う機会は増え続けている。神経心理検査は、高次脳機能の十分な知識と熟達した検査技能を併せ持つ専門家が行う必要があるが、対象者の多さに比して数が不足している。このアンバランスを解決する一つの方法が、遠隔技術を用いた検査の実施である。新型コロナウイルスの感染拡大により医療機関などの受診に制限が生じている現状において、その意義はさらに高まったと言える。本稿では、ビデオ会議システムを用いて高齢者に行う神経心理検査（以下、遠隔検査）について、対面での検査と比較した信頼性に関するレビュー、利用満足度に関するレビュー、具体的な実施手続きと留意点について、自験例を含め報告した。結果、遠隔検査は、認知症者を対象に行われた研究であっても高い信頼性が得られていた。利用満足度については概ね良好な満足度が得られているが、スピーカーを通した検査者の声の聞き取りにくさや心的負担などの否定的な意見も散見された。遠隔検査の実施手続きと留意点については、遠隔精神科医療手引書策定タスクフォースが作成した精神科遠隔（オンライン）診療手引きを参照することを推奨したい。今後、適切な手続きに従った遠隔検査が全国に普及し、さらに均てん化されることを期待したい。

What Can We Tell About the Effect of Electroconvulsive Therapy on the Human Hippocampus?

Takamiya A., Kishimoto T., Mimura M.

Clinical EEG and Neuroscience （Clinical EEG and Neuroscience） 54 （ 6 ） 15500594211044066 - 593 2021年

ISSN 15500594

Electroconvulsive therapy (ECT) is the most effective antidepressant treatment, although its mechanisms of action remain unclear. Since 2010, several structural magnetic resonance imaging studies based on a neuroplastic hypothesis have consistently reported increases in the hippocampal volume following ECT. Moreover, volume increases in the human dentate gyrus, where neurogenesis occurs, have also been reported. These results are in line with the preclinical findings of ECT-induced neuroplastic changes, including neurogenesis, gliogenesis, synaptogenesis, and angiogenesis, in rodents and nonhuman primates. Despite this robust evidence of an effect of ECT on hippocampal plasticity, the clinical relevance of these human hippocampal changes continues to be questioned. This narrative review summarizes recent findings regarding ECT-induced hippocampal volume changes. Furthermore, this review also discusses methodological considerations and future directions in this field.

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Quantum Kinetic Equilibrium

Chad T. Kishimoto, Heather Hodlin, Olexiy Dvornikov

2020年11月

We solved the Quantum Kinetic Equations (QKEs) for an active-sterile neutrino
system in the early universe. While on the surface this may seem to be an
overly simplistic system, other linear two-state systems can be mapped onto the
active-sterile system. In the early universe, we find that solutions to the
QKEs are well described by an adiabatic approximation where the off-diagonal
terms of the density operator are constant on short (oscillation and/or
scattering) timescales, but may slowly evolve on long (expansion) timescales.
This "quantum kinetic equilibrium" attains as the quantum development of phase
balances with the kinetic destruction of phase. In this work, we introduce and
assess this equilibrium ansatz as the neutrino states evolve in the early
universe with a non-zero lepton number, engendering level crossings that result
in scattering-induced active-sterile neutrino transformation.

Virtual reality exposure therapy for social anxiety disorder: A systematic review and meta-Analysis

Horigome T., Kurokawa S., Sawada K., Kudo S., Shiga K., Mimura M., Kishimoto T.

Psychological Medicine （Psychological Medicine） 50 （ 15 ） 2487 - 2497 2020年11月

ISSN 00332917

Copyright © The Author(s) 2020. Published by Cambridge University Press. Background Virtual reality exposure therapy (VRET) is currently being used to treat social anxiety disorder (SAD); however, VRET's magnitude of efficacy, duration of efficacy, and impact on treatment discontinuation are still unclear. Methods We conducted a meta-Analysis of studies that investigated the efficacy of VRET for SAD. The search strategy and analysis method are registered at PROSPERO (#CRD42019121097). Inclusion criteria were: (1) studies that targeted patients with SAD or related phobias; (2) studies where VRET was conducted for at least three sessions; (3) studies that included at least 10 participants. The primary outcome was social anxiety evaluation score change. Hedges' g and its 95% confidence intervals were calculated using random-effect models. The secondary outcome was the risk ratio for treatment discontinuation. Results Twenty-Two studies (n = 703) met the inclusion criteria and were analyzed. The efficacy of VRET for SAD was significant and continued over a long-Term follow-up period: Hedges' g for effect size at post-intervention,-0.86 (-1.04 to-0.68); three months post-intervention,-1.03 (-1.35 to-0.72); 6 months post-intervention,-1.14 (-1.39 to-0.89); and 12 months post-intervention,-0.74 (-1.05 to-0.43). When compared to in vivo exposure, the efficacy of VRET was similar at post-intervention but became inferior at later follow-up points. Participant dropout rates showed no significant difference compared to in vivo exposure. Conclusion VRET is an acceptable treatment for SAD patients that has significant, long-lasting efficacy, although it is possible that during long-Term follow-up, VRET efficacy lessens as compared to in vivo exposure.

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Safety/tolerability of antipsychotics in the treatment of adult patients with major depressive disorder: a systematic review and meta-analysis

Hagi K., Kishimoto T., Kurokawa S., Correll C. U.

EUROPEAN NEUROPSYCHOPHARMACOLOGY 40 S184 - S185 2020年11月

ISSN 0924-977X

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Risk/benefit balance of antipsychotics in the treatment of adult patients with major depressive disorder: a systematic review and meta-analysis

Kishimoto T., Hagi K., Kurokawa S., Kane J. M., Correll C. U.

EUROPEAN NEUROPSYCHOPHARMACOLOGY 40 S185 - S185 2020年11月

ISSN 0924-977X

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Long-acting injectable vs. oral antipsychotics for preventing rehospitalisation in schizophrenia: a meta-analysis of randomised, mirror-image, and cohort studies

Kishimoto T., Hagi K., Kane J. M., Correll C. U.

EUROPEAN NEUROPSYCHOPHARMACOLOGY 40 S315 - S316 2020年11月

ISSN 0924-977X

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Dose-response relationships of antipsychotic drugs for major depressive disorder: a systematic review and meta-analysis

Kurokawa S., Kishimoto T., Hagi K., Kane J., Correll C.

EUROPEAN NEUROPSYCHOPHARMACOLOGY 40 S253 - S253 2020年11月

ISSN 0924-977X

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Safety of Psychotropic Medications in People With COVID-19: Evidence Review and Practical Recommendations.

Ostuzzi G, Papola D, Gastaldon C, Schoretsanitis G, Bertolini F, Amaddeo F, Cuomo A, Emsley R, Fagiolini A, Imperadore G, Kishimoto T, Michencigh G, Nosé M, Purgato M, Serdar D, Stubbs B, Taylor D, Thornicroft G, Ward PB, Hiemke C, Correll CU, Barbui C

Focus (American Psychiatric Publishing) 18 （ 4 ） 466 - 481 2020年10月

ISSN 1541-4094

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Effects of Psychotropics on the Microbiome in Patients with Depression and Anxiety: Considerations in a Naturalistic Clinical Setting.

Tomizawa Y, Kurokawa S, Ishii D, Miyaho K, Ishii C, Sanada K, Fukuda S, Mimura M, Kishimoto T

The international journal of neuropsychopharmacology （The international journal of neuropsychopharmacology） 24 （ 2 ） 97 - 107 2020年09月

ISSN 1461-1457

© The Author(s) 2020. Published by Oxford University Press on behalf of CINP. BACKGROUND: The antibacterial effects of psychotropics may be part of their pharmacological effects when treating depression. However, limited studies have focused on gut microbiota in relation to prescribed medication. METHOD: We longitudinally investigated the relationship between patients' prescribed medications and intestinal bacterial diversity in a naturalistic treatment course for patients with major depressive disorders and anxiety disorders. Patients were recruited and their stool was collected at 3 time points during their usual psychiatric treatments. Gut microbiota were analyzed using 16S rRNA gene sequencing. We examined the impact of psychotropics (i.e., antidepressants, anxiolytics, antipsychotics) on their gut microbial diversity and functions. RESULTS: We collected 246 stool samples from 40 patients. Despite no differences in microbial diversity between medication groups at the baseline, over the course of treatment, phylogenic diversity whole-tree diversity decreased in patients on antipsychotics compared with patients without (P = .027), and beta diversity followed this trend. Based on a fixed-effect model, antipsychotics predicted microbial diversity; the higher doses correlated with less diversity based on the Shannon index and phylogenic diversity whole tree (estimate = -0.00254, SE = 0.000595, P < .0001; estimate = -0.02644, SE = 0.00833, P = .002, respectively). CONCLUSION: Antipsychotics may play a role in decreasing the alpha diversity of the gut microbiome among patients with depression and anxiety, and our results indicate a relationship with medication dosage. Future studies are warranted and should consider patients' types and doses of antipsychotics in order to further elucidate the mechanisms of gut-brain interactions in psychiatric disorders.

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A study on energy resolution of CANDLES detector

B. T. Khai, S. Ajimura, W. M. Chan, K. Fushimi, R. Hazama, H. Hiraoka, T. Iida, K. Kanagawa, H. Kino, T. Kishimoto, T. Maeda, K. Nakajima, M. Nomachi, I. Ogawa, T. Ohata, K. Suzuki, Y. Takemoto, Y. Takihira, Y. Tamagawa, M. Tozawa, M. Tsuzuki, S. Umehara, S. Yoshida

2020年09月

In a neutrino-less double-beta-decay ($0\nu\beta\beta$) experiment, an
irremovable two-neutrino double-beta-decay ($2\nu\beta\beta$) background
surrounds the Q-value of the double beta decay isotope. The energy resolution
must be improved to differentiate between $0\nu\beta\beta$ and $2\nu\beta\beta$
events. CAlcium fluoride for studies of Neutrino and Dark matters by Low Energy
Spectrometer (CANDLES) discerns the $0\nu\beta\beta$ of $^{48}$Ca using a
CaF$_2$ scintillator as the detector and source. Photomultiplier tubes (PMTs)
collect scintillation photons. Ideally, the energy resolution should equal the
statistical fluctuation of the number of photoelectrons. At the Q-value of
$^{48}$Ca, the current energy resolution (2.6%) exceeds this fluctuation
(1.6%). Because of CaF$_2$'s long decay constant of 1000 ns, a signal
integration in 4000 ns is used to calculate the energy. The baseline
fluctuation ($\sigma_{\rm baseline}$) is accumulated in the signal integration,
degrading the energy resolution. Therefore, this paper studies $\sigma_{\rm
baseline}$ in the CANDLES detector, which has a severe effect (1%) at the
Q-value of $^{48}$Ca. To avoid $\sigma_{\rm baseline}$, photon counting can be
used to obtain the number of photoelectrons in each PMT; however, a significant
photoelectron signal overlapping probability in each PMT causes missing
photoelectrons in counting and reduces the energy resolution. "Partial photon
counting" reduces $\sigma_{\rm baseline}$ and minimizes photoelectron loss. We
thus obtain improved energy resolutions of 4.5--4.0% at 1460.8 keV
($\gamma$-ray of $^{40}$K), and 3.3--2.9% at 2614.5 keV ($\gamma$-ray of
$^{208}$Tl). The energy resolution at the Q-value shows an estimated
improvement of 2.2%, with improved detector sensitivity by factor 1.09 for the
$0\nu\beta\beta$ half-life of $^{48}$Ca.

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Prescription patterns in patients with schizophrenia in Japan: First-quality indicator data from the survey of “Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment (EGUIDE)” project

Ichihashi K., Hori H., Hasegawa N., Yasuda Y., Yamamoto T., Tsuboi T., Iwamoto K., Kishimoto T., Horai T., Yamada H., Sugiyama N., Nakamura T., Tsujino N., Nemoto K., Oishi S., Usami M., Katsumoto E., Yamamori H., Tomita H., Suwa T., Furihata R., Inagaki T., Fujita J., Onitsuka T., Miura K., Matsumoto J., Ohi K., Matsui Y., Takaesu Y., Hashimoto N., Iga J., Ogasawara K., Yamada H., Watanabe K., Inada K., Hashimoto R.

Neuropsychopharmacology Reports （Neuropsychopharmacology Reports） 40 （ 3 ） 281 - 286 2020年09月

© 2020 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Society of NeuropsychoPharmacology. Background: Guideline for Pharmacological Therapy for Schizophrenia was published by the Japanese Society of Neuropsychopharmacology in 2015. “Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment (EGUIDE)” project aimed to standardize medical practice using quality indicators (QIs) as indices to evaluate the quality of medical practice. In this study, we have reported the quality indicator values of prescription before the beginning of the guideline lectures in the EGUIDE project to ascertain the baseline status of treating patients with schizophrenia. Methods: A cross-sectional, retrospective case record survey was conducted, involving 1164 patients with schizophrenia at the time of discharge. We checked all types and dosage of psychotropic drugs. Results: Forty-three percent of patients had antipsychotic polypharmacy, and substantial concomitant medication was observed (antidepressants; 8%, mood stabilizers: 37%, anxiolytics or hypnotics: 68%). Conclusions: In the results obtained in this study, we plant to report changes in the effectiveness of education in the EGUIDE project near the future.

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Using speech recognition technology to investigate the association between timing-related speech features and depression severity

Yamamoto M., Takamiya A., Sawada K., Yoshimura M., Kitazawa M., Liang K.C., Fujita T., Mimura M., Kishimoto T.

PLoS ONE （PLoS ONE） 15 （ 9 September ） e0238726 2020年09月

ISSN 1932-6203

© 2020 Yamamoto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background There are no reliable and validated objective biomarkers for the assessment of depression severity. We aimed to investigate the association between depression severity and timing-related speech features using speech recognition technology. Method Patients with major depressive disorder (MDD), those with bipolar disorder (BP), and healthy controls (HC) were asked to engage in a non-structured interview with research psychologists. Using automated speech recognition technology, we measured three timing-related speech features: speech rate, pause time, and response time. The severity of depression was assessed using the Hamilton Depression Rating Scale 17-item version (HAMD-17). We conducted the current study to answer the following questions: 1) Are there differences in speech features among MDD, BP, and HC? 2) Do speech features correlate with depression severity? 3) Do changes in speech features correlate with within-subject changes in depression severity? Results We collected 1058 data sets from 241 individuals for the study (97 MDD, 68 BP, and 76 HC). There were significant differences in speech features among groups; depressed patients showed slower speech rate, longer pause time, and longer response time than HC. All timing-related speech features showed significant associations with HAMD-17 total scores. Longitudinal changes in speech rate correlated with changes in HAMD-17 total scores. Conclusions Depressed individuals showed longer response time, longer pause time, and slower speech rate than healthy individuals, all of which were suggestive of psychomotor retardation. Our study suggests that speech features could be used as objective biomarkers for the assessment of depression severity.

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Safety of psychotropic medications in people with COVID-19: evidence review and practical recommendations

Ostuzzi Giovanni, Papola Davide, Gastaldon Chiara, Schoretsanitis Georgios, Bertolini Federico, Amaddeo Francesco, Cuomo Alessandro, Emsley Robin, Fagiolini Andrea, Imperadore Giuseppe, Kishimoto Taishiro, Michencigh Giulia, Nose Michela, Purgato Marianna, Serdar Dursun, Stubbs Brendon, Taylor David, Thornicroft Graham, Ward Philip B., Hiemke Christoph, Correll Christoph U., Barbui Corrado

BMC MEDICINE 18 （ 1 ） 2020年07月

ISSN 1741-7015

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Safety of psychotropic medications in people with COVID-19: evidence review and practical recommendations.

Ostuzzi G, Papola D, Gastaldon C, Schoretsanitis G, Bertolini F, Amaddeo F, Cuomo A, Emsley R, Fagiolini A, Imperadore G, Kishimoto T, Michencigh G, Nosé M, Purgato M, Dursun S, Stubbs B, Taylor D, Thornicroft G, Ward PB, Hiemke C, Correll CU, Barbui C

BMC medicine 18 （ 1 ） 215 2020年07月

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Safety of psychotropic medications in people with COVID-19: Evidence review and practical recommendations

Ostuzzi G., Papola D., Gastaldon C., Schoretsanitis G., Bertolini F., Amaddeo F., Cuomo A., Emsley R., Fagiolini A., Imperadore G., Kishimoto T., Michencigh G., Nosé M., Purgato M., Serdar D., Stubbs B., Taylor D., Thornicroft G., Ward P.B., Hiemke C., Correll C.U., Barbui C.

BMC Medicine （BMC Medicine） 18 （ 1 ） 2020年07月

© 2020 The Author(s). Background: The novel coronavirus pandemic calls for a rapid adaptation of conventional medical practices to meet the evolving needs of such vulnerable patients. People with coronavirus disease (COVID-19) may frequently require treatment with psychotropic medications, but are at the same time at higher risk for safety issues because of the complex underlying medical condition and the potential interaction with medical treatments. Methods: In order to produce evidence-based practical recommendations on the optimal management of psychotropic medications in people with COVID-19, an international, multi-disciplinary working group was established. The methodology of the WHO Rapid Advice Guidelines in the context of a public health emergency and the principles of the AGREE statement were followed. Available evidence informing on the risk of respiratory, cardiovascular, infective, hemostatic, and consciousness alterations related to the use of psychotropic medications, and drug-drug interactions between psychotropic and medical treatments used in people with COVID-19, was reviewed and discussed by the working group. Results: All classes of psychotropic medications showed potentially relevant safety risks for people with COVID-19. A set of practical recommendations was drawn in order to inform frontline clinicians on the assessment of the anticipated risk of psychotropic-related unfavorable events, and the possible actions to take in order to effectively manage this risk, such as when it is appropriate to avoid, withdraw, switch, or adjust the dose of the medication. Conclusions: The present evidence-based recommendations will improve the quality of psychiatric care in people with COVID-19, allowing an appropriate management of the medical condition without worsening the psychiatric condition and vice versa.

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Modulation of hippocampal functional connectivity and depressive symptom improvement following ECT

Takamiya A., Kishimoto T., Hirano J., Nakajima K., Katayama N., Kikuchi T., Yamagata B., Nakagawa A., Mimura M.

EUROPEAN PSYCHIATRY 63 S373 - S373 2020年07月

ISSN 0924-9338

Speech quality feature analysis for classification of depression and dementia patients

Sumali B., Mitsukura Y., Liang K.C., Yoshimura M., Kitazawa M., Takamiya A., Fujita T., Mimura M., Kishimoto T.

Sensors (Switzerland) （Sensors (Switzerland)） 20 （ 12 ） 1 - 17 2020年06月

ISSN 14248220

© MDPI AG. All rights reserved. Loss of cognitive ability is commonly associated with dementia, a broad category of progressive brain diseases. However, major depressive disorder may also cause temporary deterioration of one’s cognition known as pseudodementia. Differentiating a true dementia and pseudodementia is still difficult even for an experienced clinician and extensive and careful examinations must be performed. Although mental disorders such as depression and dementia have been studied, there is still no solution for shorter and undemanding pseudodementia screening. This study inspects the distribution and statistical characteristics from both dementia patient and depression patient, and compared them. It is found that some acoustic features were shared in both dementia and depression, albeit their correlation was reversed. Statistical significance was also found when comparing the features. Additionally, the possibility of utilizing machine learning for automatic pseudodementia screening was explored. The machine learning part includes feature selection using LASSO algorithm and support vector machine (SVM) with linear kernel as the predictive model with age-matched symptomatic depression patient and dementia patient as the database. High accuracy, sensitivity, and specificity was obtained in both training session and testing session. The resulting model was also tested against other datasets that were not included and still performs considerably well. These results imply that dementia and depression might be both detected and differentiated based on acoustic features alone. Automated screening is also possible based on the high accuracy of machine learning results.

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Effects of Psychotropics on the Microbiome in Patients With Depression and Anxiety: a Naturalistic Prospective Study

Kurokawa Shunya, Tomizawa Yoshihiro, Ishii Daiki, Miyaho Katsuma, Sanada Kenji, Mimura Masaru, Kishimoto Taishiro

BIOLOGICAL PSYCHIATRY 87 （ 9 ） S279 - S280 2020年05月

ISSN 0006-3223

Examination of Language Characteristics Among Patients With Alzheimer's Disease Using Natural Language Processing

Momota Yuki, Isa Shimpei, Eguchi Yoko, Kitazawa Momoko, Mimura Masaru, Kishimoto Taishiro

BIOLOGICAL PSYCHIATRY 87 （ 9 ） S285 - S285 2020年05月

ISSN 0006-3223

Gut microbiota and majore depressive disorder: A systematic review and meta-analysis

Sanada K., Nakajima S., Kurokawa S., Barceló-Soler A., Ikuse D., Hirata A., Yoshizawa A., Tomizawa Y., Salas-Valero M., Noda Y., Mimura M., Iwanami A., Kishimoto T.

Journal of Affective Disorders （Journal of Affective Disorders） 266 1 - 13 2020年04月

ISSN 01650327

© 2020 Elsevier B.V. Background: Growing attention has been paid to the field of gut microbiota for mental disorders over the last decade. However, to our knowledge, no studies have conducted systematic reviews on the association between gut microbiota and major depressive disorder (MDD) in both interventional and non-interventional studies. Methods: We conducted a systematic review and meta-analysis of 16 studies (10 observational [701 participants] and six interventional trials [302 participants]) examining gut microbiota in patients with MDD. The primary outcome measures were differences in the profile of microbiota inthe observational studies, and symptom changes for depression between pre- and post-intervention with probiotics in the interventional trials. Results: In the observational studies, significant reductions in several taxa at the family and genus levels were observed in patients with MDD compared to non-depressed controls. In the interventional studies with probiotics, a significant improvement was found in depressive symptomatology compared to controls (SMD = .-1.62, 95% CI = .-2.73 to -0.51, p< 0.01). Limitations: Lack of consideration of the effects of diet and pharmacotherapy was a possible limitation. Conclusions: Our results indicate that several taxa at the family and genus levels, specifically family Prevotellaceae, genus Coprococcus,and Faecalibacterium, were decreased in MDD compared to non-depressed controls in observational studies, and depressive symptoms were improved compared to controls in interventional studies with probiotics. Due to the limited number of studies, further studies considering diet and pharmacotherapy are needed to explore the relationships between gut microbiota and MDD in humans.

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Evaluating the severity of depressive symptoms using upper body motion captured by RGB-depth sensors and machine learning in a clinical interview setting: A preliminary study

Horigome T., Sumali B., Kitazawa M., Yoshimura M., Liang K.c., Tazawa Y., Fujita T., Mimura M., Kishimoto T.

Comprehensive Psychiatry （Comprehensive Psychiatry） 98 152169 2020年04月

ISSN 0010440X

© 2020 The Authors Background: Mood disorders have long been known to affect motor function. While methods to objectively assess such symptoms have been used in experiments, those same methods have not yet been applied in clinical practice because the methods are time-consuming, labor-intensive, or invasive. Methods: We videotaped the upper body of each subject using a Red-Green-Blue-Depth (RGB-D) sensor during a clinical interview setting. We then examined the relationship between depressive symptoms and body motion by comparing the head motion of patients with major depressive disorders (MDD) and bipolar disorders (BD) to the motion of healthy controls (HC). Furthermore, we attempted to predict the severity of depressive symptoms by using machine learning. Results: A total of 47 participants (HC, n = 16; MDD, n = 17; BD, n = 14) participated in the study, contributing to 144 data sets. It was found that patients with depression move significantly slower compared to HC in the 5th percentile and 50th percentile of motion speed. In addition, Hamilton Depression Rating Scale (HAMD)-17 scores correlated with 5th percentile, 50th percentile, and mean speed of motion. Moreover, using machine learning, the presence and/or severity of depressive symptoms based on HAMD-17 scores were distinguished by a kappa coefficient of 0.37 to 0.43. Limitations: Limitations include the small number of subjects, especially the number of severe cases and young people. Conclusions: The RGB-D sensor captured some differences in upper body motion between depressed patients and controls. If much larger samples are accumulated, machine learning may be useful in identifying objective measures for depression in the future.

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The energy calibration system for CANDLES using (n, γ) reaction

T. Iida, K. Mizukoshi, T. Ohata, T. Uehara, T. Batpurev, W. M. Chan, K. Fushimi, R. Hazama, M. Ishikawa, H. Kakubata, K. Kanagawa, S. Katagiri, B. T. Khai, T. Kishimoto, X. Li, T. Maeda, K. Matsuoka, K. Morishita, M. Moser, K. Nakajima, M. Nomachi, I. Ogawa, M. Shokati, K. Suzuki, Y. Takemoto, Y. Takihira, Y. Tamagawa, K. Tetsuno, V. T. T. Trang, S. Umehara, S. Yoshida

2020年03月

CAlcium fluoride for the study of Neutrinos and Dark matters by Low-energy
Spectrometer (CANDLES) searches for neutrino-less double beta decay of
$^{48}$Ca using a CaF$_2$ scintillator array. A high Q-value of $^{48}$Ca at
4,272 keV enabled us to achieve very low background condition, however, at the
same it causes difficulties in calibrating the detector's Q-value region
because of the absence of a standard high-energy $\gamma$-ray source.
Therefore, we have developed a novel calibration system based on $\gamma$-ray
emission by neutron capture on $^{28}$Si, $^{56}$Fe and $^{58}$Ni nuclei. In
the paper, we report the development of the new calibration system as well as
the results of energy calibration in CANDLES up to 9 MeV.

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Predicting Individual Remission After Electroconvulsive Therapy Based on Structural Magnetic Resonance Imaging: A Machine Learning Approach.

Takamiya A, Liang KC, Nishikata S, Tarumi R, Sawada K, Kurokawa S, Hirano J, Yamagata B, Mimura M, Kishimoto T

The journal of ECT （Journal of ECT） 36 （ 3 ） 205 - 210 2020年02月

研究論文（学術雑誌）, 査読有り, ISSN 1095-0680

Objective To identify important clinical or imaging features predictive of an individual's response to electroconvulsive therapy (ECT) by utilizing a machine learning approach. Methods Twenty-seven depressed patients who received ECT were recruited. Clinical demographics and pretreatment structural magnetic resonance imaging (MRI) data were used as candidate features to build models to predict remission and post-ECT Hamilton Depression Rating Scale scores. Support vector machine and support vector regression with elastic-net regularization were used to build models using (i) only clinical features, (ii) only MRI features, and (iii) both clinical and MRI features. Consistently selected features across all individuals were identified through leave-one-out cross-validation. Results Compared with models that include only clinical variables, the models including MRI data improved the prediction of ECT remission: the prediction accuracy improved from 70% to 93%. Features selected consistently across all individuals included volumes in the gyrus rectus, the right anterior lateral temporal lobe, the cuneus, and the third ventricle, as well as 2 clinical features: psychotic features and family history of mood disorder. Conclusions Pretreatment structural MRI data improved the individual predictive accuracy of ECT remission, and only a small subset of features was important for prediction.

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Evaluating depression with multimodal wristband-type wearable device: screening and assessing patient severity utilizing machine-learning

Tazawa Y., Liang K., Yoshimura M., Kitazawa M., Kaise Y., Takamiya A., Kishi A., Horigome T., Mitsukura Y., Mimura M., Kishimoto T.

Heliyon （Heliyon） 6 （ 2 ） e03274 2020年02月

研究論文（学術雑誌）, 査読有り, ISSN 24058440

© 2020 Objective: We aimed to develop a machine learning algorithm to screen for depression and assess severity based on data from wearable devices. Methods: We used a wearable device that calculates steps, energy expenditure, body movement, sleep time, heart rate, skin temperature, and ultraviolet light exposure. Depressed patients and healthy volunteers wore the device continuously for the study period. The modalities were compared hourly between patients and healthy volunteers. XGBoost was used to build machine learning models and 10-fold cross-validation was applied for the validation. Results: Forty-five depressed patients and 41 healthy controls participated, creating a combined 5,250 days' worth of data. Heart rate, steps, and sleep were significantly different between patients and healthy volunteers in some comparisons. Similar differences were also observed longitudinally when patients' symptoms improved. Based on seven days' data, the model identified symptomatic patients with 0.76 accuracy and predicted Hamilton Depression Rating Scale-17 scores with a 0.61 correlation coefficient. Skin temperature, sleep time-related features, and the correlation of those modalities were the most significant features in machine learning. Limitations: The small number of subjects who participated in this study may have weakened the statistical significance of the study. There are differences in the demographic data among groups although we performed a correction for multiple comparisons. Validation in independent datasets was not performed, although 10-fold cross validation with the internal data was conducted. Conclusion: The results indicated that utilizing wearable devices and machine learning may be useful in identifying depression as well as assessing severity.

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Autism Spectrum Disorder’s Severity Prediction Model Using Utterance Features for Automatic Diagnosis Support

Sakishita M., Ogawa C., Tsuchiya K., Iwabuchi T., Kishimoto T., Kano Y.

Studies in Computational Intelligence （Studies in Computational Intelligence） 843 83 - 95 2020年

ISSN 1860949X

© Springer Nature Switzerland AG 2020. Diagnoses of autism spectrum disorder (ASD) are difficult due to difference of interviewers and environments, etc. We show relations between utterance features and ASD severity scores, which were manually given by clinical psychologists. These scores are based on the Autism Diagnostic Observation Schedule (ADOS), which is the standard metrics for symptom evaluation for subjects who are suspected as ASD. We built our original corpus where we transcribed voice records of our ADOS evaluation experiment movies. Our corpus is the world largest as speech/dialog of ASD subjects, and there has been no such ADOS corpus available in Japanese language as far as we know. We investigated relationships between ADOS scores (severity) and our utterance features, automatically estimated their scores using support vector regression (SVR). Our average estimation errors were around error rates that human ADOS experts are required not to exceed. Because our detailed analysis for each part of the ADOS test (â€œpuzzle toy assembly + story tellingâ€ part and the â€œdepiction of a pictureâ€ part) shows different error rates, effectiveness of our features would depend on the contents of the records. Our entire results suggest a new automatic way to assist humansâ€™ diagnosis, which could help supporting language rehabilitation for individuals with ASD in future.

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Large-Scale Dialog Corpus Towards Automatic Mental Disease Diagnosis

Sakishita M., Kishimoto T., Takinami A., Eguchi Y., Kano Y.

Studies in Computational Intelligence （Studies in Computational Intelligence） 843 111 - 118 2020年

研究論文（国際会議プロシーディングス）, ISSN 1860949X

© Springer Nature Switzerland AG 2020. Recently, the number of people who are diagnosed as mental diseases is increasing. Efficient and objective diagnosis is important to start medical treatments in earlier stages. However, mental disease diagnosis is difficult to quantify criteria, because it is performed through conversations with patients, not by physical surveys. We aim to automate mental disease diagnosis in order to resolve these issues. We recorded conversations between psychologists and subjects to build our diagnosis speech corpus. Our subjects include healthy persons, people with mental diseases of depression, bipolar disorder, schizophrenia, anxiety and dementia. All of our subjects are diagnosed by doctors of psychiatry. Then we made accurate transcription manually, adding utterance time stamps, linguistic and non-linguistic annotations. Using our corpus, we performed feature analysis to find characteristics for each disease. We also tried automatic mental disease diagnosis by machine learning, while the number of sample data is few because we were still in our pilot study phase. We will increase the number of subjects in future.

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発話特徴を用いた自閉スペクトラム症の重症度推測システム

﨑下雅仁, 小川ちひろ, 土屋賢治, 岩渕俊樹, 岸本泰士郎, 狩野芳伸.

人工知能学会論文誌 35 （ 3 ） 2020年

研究論文（学術雑誌）, 査読有り

Neuronal network mechanisms associated with depressive symptom improvement following electroconvulsive therapy

Takamiya A., Kishimoto T., Hirano J., Nishikata S., Sawada K., Kurokawa S., Yamagata B., Kikuchi T., Mimura M.

Psychological Medicine （Psychological Medicine） 51 （ 16 ） 1 - 8 2020年

ISSN 00332917

Copyright © The Author(s) 2020. Published by Cambridge University Press. BackgroundElectroconvulsive therapy (ECT) is the most effective antidepressant treatment for severe depression. Although recent structural magnetic resonance imaging (MRI) studies have consistently reported ECT-induced hippocampal volume increases, most studies did not find the association of the hippocampal volume changes with clinical improvement. To understand the underlying mechanisms of ECT action, we aimed to identify the longitudinal effects of ECT on hippocampal functional connectivity (FC) and their associations with clinical improvement.MethodsResting-state functional MRI was acquired before and after bilateral ECT in 27 depressed individuals. A priori hippocampal seed-based FC analysis and a data-driven multivoxel pattern analysis (MVPA) were conducted to investigate FC changes associated with clinical improvement. The statistical threshold was set at cluster-level false discovery rate-corrected p < 0.05.ResultsDepressive symptom improvement after ECT was positively associated with the change in the right hippocampus-ventromedial prefrontal cortex FC, and negatively associated with the right hippocampus-superior frontal gyrus FC. MVPA confirmed the results of hippocampal seed-based analyses and identified the following additional clusters associated with clinical improvement following ECT: the thalamus, the sensorimotor cortex, and the precuneus.ConclusionsECT-induced change in the right frontotemporal connectivity and thalamocortical connectivity, and changes in the nodes of the default mode network were associated with clinical improvement. Modulation of these networks may explain the underlying mechanisms by which ECT exert its potent and rapid antidepressant effect.

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Autism spectrum disorder’s severity prediction system using utterance features

Sakishita M., Ogawa C., Tsuchiya K.J., Iwabuchi T., Kishimoto T., Kano Y.

Transactions of the Japanese Society for Artificial Intelligence （Transactions of the Japanese Society for Artificial Intelligence） 35 （ 3 ） B - J45_1-11 2020年

ISSN 13460714

© 2020, Japanese Society for Artificial Intelligence. All rights reserved. In recent years, population with autism spectrum disorder (ASD) are growing explosively, and diagnosis of ASD is difficult due to difference of interviewers and environments, etc. We show relations between utterance features and ASD severity scores, which were manually given by a clinical psychologist. These scores are of the Autism Diagnostic Observation Schedule (ADOS), which is one of the standard metrics for symptom evaluation for subjects who are suspected as ASD. We built our original corpus where we transcribed voice records of our ADOS evaluation experiment movies. Our corpus is the world largest as speech/dialog of ASD subjects, and there has been no such ADOS corpus available in Japanese language as far as we know. We investigated relationships between ADOS scores (severity) and utterance features we defined. Our system automatically estimated their scores using support vector regression (SVR). Our average estimation errors were around error rates that human ADOS experts are required not to exceed. Because our detailed analysis for each part of the ADOS test (“puzzle toy assembly + story telling” part and the “depiction of a picture” part) shows different error rates, effectiveness of our features would depend on the contents of the records. By comparing an ADOS score prediction result of adults and adults with that of children, we showed common features of ADOS scores between children and adults. Our entire results suggest a new automatic way to assist humans’ diagnosis, which could help supporting language rehabilitation for patients with ASD in future.

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Changes in Telepsychiatry Regulations during the COVID-19 Pandemic: 17 Countries and Regions' Approaches to an Evolving Healthcare Landscape

Kinoshita S., Cortright K., Crawford A., Mizuno Y., Yoshida K., Hilty D., Guinart D., Torous J., Correll C.U., Castle D.J., Rocha D., Yang Y., Xiang Y.T., Kølbæk P., Dines D., Elshami M., Jain P., Kallivayalil R., Solmi M., Favaro A., Veronese N., Seedat S., Shin S., De Pablo G.S., Chang C.H., Su K.P., Karas H., Kane J.M., Yellowlees P., Kishimoto T.

Psychological Medicine （Psychological Medicine） 52 （ 13 ） 1 - 8 2020年

ISSN 00332917

© 2020 American Medical Association. All rights reserved. Background: During the COVID-19 pandemic, the use of telemedicine as a way to reduce COVID-19 infections was noted and consequently deregulated. However, the degree of telemedicine regulation varies from country to country, which may alter the widespread use of telemediine. This study aimed to clarify the telepsychiatry regulations for each collaborating country/region before and during the COVID-19 pandemic. Methods: We used snowball sampling within a global network of international telepsychiatry experts. Thirty collaborators from 17 different countries/regions responded to a questionnaire on barriers to the use and implementation of telepsychiatric care, including policy factors such as regulations and reimbursement at the end of 2019 and as of May 2020. Results: Thirteen of 17 regions reported a relaxation of regulations due to the pandemic; consequently, all regions surveyed stated that telepsychiatry was now possible within their public healthcare systems. In some regions, restrictions on prescription medications allowed via telepsychiatry were eased, but in 11 of the 17 regions, there were still restrictions on prescribing medications via telepsychiatry. Lower insurance reimbursement amounts for telepsychiatry consultations versus in-person consultations were reevaluated in 4 regions, and consequently, in 15 regions telepsychiatry services were reimbursed at the same rate (or higher) than in-person consultations during the COVID-19 pandemic. Conclusions: Our results confirm that, due to COVID-19, the majority of countries surveyed are altering telemedicine regulations that had previously restricted the spread of telemedicine. These findings provide information that could guide future policy and regulatory decisions, that facilitate greater scale and spread of telepsychiatry globally.

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機械学習を用いた自殺予防の可能性とその問題点

木下翔太郎, 岸本泰士郎

日本生物学的精神医学会誌（日本生物学的精神医学会） 31 （ 3 ） 141 - 146 2020年

ISSN 2186-6619

自殺者の90%以上は精神疾患を有しているとされており，精神科医にとって自殺の予防は最重要課題の一つである。しかし，精神神経科領域は，診断や重症度評価の客観的指標となるバイオマーカーに乏しく，複合的な要因によって引き起こされる自殺もまた正確な予測が困難とされてきた。近年，自殺予防において，機械学習（machine learning）を用いた研究が数多く行われるようになってきており，画像データや，自然言語処理（natural language processing）を用いた個人の日記やSNSへの投稿に関する研究など，従来にはない試みも出てきている。本稿では，機械学習を用いた自殺予防に関する新しい知見について紹介しつつ，社会への実装に際し検討すべき倫理的・法的・社会的な課題（ethical legal and social implications：ELSI）についても触れる。

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Electroconvulsive Therapy for Parkinson's Disease: A Systematic Review and Meta-Analysis

Takamiya A., Seki M., Kudo S., Yoshizaki T., Nakahara J., Mimura M., Kishimoto T.

Movement Disorders （Movement Disorders） 36 （ 1 ） 50 - 58 2020年

ISSN 08853185

© 2020 International Parkinson and Movement Disorder Society Background: Electroconvulsive therapy (ECT) is a well-established treatment for psychiatric disorders, including depression and psychosis. ECT has been reported to be effective in treating such psychiatric symptoms in patients with Parkinson's disease (PD) and has been also reported to be effective in treating motor symptoms. The aim of the study is to summarize previous clinical studies investigating the efficacy of ECT for symptoms in patients with PD. Methods: A systematic review and meta-analysis of any study designs assessing motor and/or non-motor symptoms in patients with PD before and after ECT. Co-primary outcomes were set as motor manifestations assessed using the Unified Parkinson's Disease Rating Scale or other rating scales, and non-motor symptoms included depression and psychosis. Secondary outcomes were wearing-off phenomenon and cognitive function. The impact of ECT on those symptoms was examined by comparing the severity of the symptoms before and after ECT using a random effect model and was expressed in standardized mean difference. Results: Of 1219 identified citations, 14 studies (n = 129; 1 randomized controlled study, 9 prospective observational studies, and 4 retrospective studies) were analyzed. The findings were as follows: ECT significantly improved motor manifestations in patients with PD, and the improvement was significant in the subpopulation without psychiatric symptoms; ECT significantly improved depression and psychosis; and ECT significantly relieved wearing-off phenomenon and did not worsen cognitive functioning. Conclusion: The current meta-analysis suggests the potential benefit of ECT on motor and non-motor symptoms in presumably complicated and difficult-to-treat subgroups. © 2020 International Parkinson and Movement Disorder Society.

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デスクワーク労働者のパフォーマンスに関連する要因の検討

志賀希子, 泉啓介, 湊和修, 吉村道孝, 北沢桃子, 三村將, 岸本泰士郎

日本心理学会大会発表論文集（公益社団法人日本心理学会） 84 （ 0 ） PQ - 020-PQ-020 2020年

【目的】本研究は「現場の負担を抑えたセンシングでストレスや幸福度を定量し健康経営オフィスを実現するシステムの開発」（日本医療研究開発機構）の中から，質問紙データを用い，労働者の日々のパフォーマンス（被験者が感じる自身の仕事の能率）と職場環境，生活習慣，ストレス，うつ，well-beingの関連を検討した。 【方法】国内11社の労働者を対象に，業務時間中に4週間調査を実施した。パフォーマンスは3件法（1：悪，2：普通，3：良）で自己申告にて毎日回答を得た。解析はパフォーマンス平均値を従属変数とした重回帰分析を行い，独立変数は性別，PC使用時間，学歴，喫煙歴，平日／休日の睡眠時間，睡眠負債，睡眠の質，気分／体調，ストレス，うつ，well-being得点とした。 【結果】被験者192名（男性103名，年齢38.9±8.4歳），パフォーマンスは2.04±0.31だった。パフォーマンスに対して気分／体調，PC使用時間，女性は正の影響，ストレスは負の影響が示された（p＜.05）。 【考案】本研究より毎日の気分や体調，PC使用時間，ストレス，性別が労働者のパフォーマンスに関連している可能性が示唆された。パフォーマンスを促進するにはこれらの要素を考慮する必要がある。

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Volume Increase of the Dentate Gyrus Induced by Electroconvulsive Therapy: Shedding Light on the Clinical Relevance of Plasticity in the Hippocampus

Takamiya A., Nuninga J., Mandl R., Sommer I., Mimura M., Kishimoto T.

The journal of ECT （The journal of ECT） 35 （ 4 ） e57 - e58 2019年12月

ISSN 1095-0680

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Volume Increase of the Dentate Gyrus Induced by Electroconvulsive Therapy Shedding Light on the Clinical Relevance of Plasticity in the Hippocampus

Takamiya Akihiro, Nuninga Jasper O., Mandl Rene C. W., Sommer Iris E. C., Mimura Masaru, Kishimoto Taishiro

JOURNAL OF ECT 35 （ 4 ） E57 - E58 2019年12月

ISSN 1095-0680

A Validation Study of the Remotely Administered Montreal Cognitive Assessment Tool in the Elderly Japanese Population

Iiboshi Kiyoko, Yoshida Kazunari, Yamaoka Yoshitaka, Eguchi Yoko, Sato Daisuke, Kishimoto Megumi, Funaki Kei, Mimura Masaru, Kishimoto Taishiro

TELEMEDICINE AND E-HEALTH （Telemedicine and e-Health） 26 （ 7 ） 1 - 9 2019年11月

ISSN 1530-5627

© MARY ANN LIEBERT, INC. Background: In an aging society, neuropsychological testing using video teleconferencing (VTC) is increasingly important. Despite the potential benefit of a VTC-administered Montreal Cognitive Assessment Tool (MoCA) to detect cognitive decline, only a limited number of studies have investigated this tool's reliability. Therefore, we aimed to evaluate the reliability of VTC-administered MoCA compared with face-to-face (FTF)-administered MoCA among elderly Japanese participants. Moreover, we examined participants' satisfaction with VTC-administered MoCA. Methods: Participants ‡60 years of age with and without cognitive impairment (i.e., those with mild cognitive impairment [MCI], those with dementia, and healthy controls [HC]) were assessed with VTC- and FTF-administered MoCA at an interval of >2 weeks and <3 months. The order effect (VTC first vs. FTF first) and time effect (first vs. second testing session), as well as several covariates such as age and years of education were controlled. Intraclass correlation coefficients (ICCs) were calculated using a mixed-effects model to assess the agreement between the two (VTC- vs. FTF-administered) groups. Participants' satisfaction with VTC-administered MoCA was examined using a Likert scale asking seven questions. Results: We included 73 participants in the study (36 men; age, 76.3 - 7.5 years). The ICC for the MoCA total score was high in the entire sample (0.85), whereas ICCs were moderate to high for the subgroups (MCI: 0.82, dementia: 0.82, and HC: 0.53). Furthermore, we found good overall participant satisfaction with VTC-administered MoCA. Discussion: VTC-administered MoCA appears viable as an alternative to FTF-administered MoCA, although further replication studies with larger sample sizes are needed.

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Survey of the effects of internet usage on the happiness of Japanese university students

Kitazawa M., Yoshimura M., Hitokoto H., Sato-Fujimoto Y., Murata M., Negishi K., Mimura M., Tsubota K., Kishimoto T.

Health and quality of life outcomes （Health and quality of life outcomes） 17 （ 1 ） 151 2019年10月

BACKGROUND: Besides research on psychiatric diseases related to problematic Internet use (PIU), a growing number of studies focus on the impact of Internet on subjective well-being (SWB). However, in previous studies on the relationship between PIU and SWB, there is little data for Japanese people specifically, and there is a lack of consideration for differences in perception of happiness due to cultural differences. Therefore, we aimed to clarify how happiness is interdependent on PIU measures, with a focus on how the concept of happiness is interpreted among Japanese people, and specifically among Japanese university students. METHODS: A paper-based survey was conducted with 1258 Japanese university students. Respondents were asked to fill out self-report scales regarding their happiness using the Interdependent Happiness Scale (IHS). The relationship between IHS and Internet use (Japanese version of the Internet addiction test, JIAT), use of social networking services, as well as social function and sleep quality (Pittsburgh Sleep Quality Index, PSQI) were sought using multiple regression analyses. RESULTS: Based on multiple regression analyses, the following factors related positively to IHS: female gender and the number of Twitter followers. Conversely, the following factors related negatively to IHS: poor sleep, high- PIU, and the number of times the subject skipped a whole day of school. CONCLUSIONS: It was shown that there was a significant negative correlation between Japanese youths' happiness and PIU. Since epidemiological research on happiness that reflects the cultural background is still scarce, we believe future studies shall accumulate similar evidence in this regard.

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Thalamic volume, resting-state activity, and their association with the efficacy of electroconvulsive therapy

Takamiya A., Kishimoto T., Liang K., Terasawa Y., Nishikata S., Tarumi R., Sawada K., Kurokawa S., Hirano J., Yamagata B., Mimura M.

Journal of Psychiatric Research （Journal of Psychiatric Research） 117 135 - 141 2019年10月

ISSN 00223956

© 2019 Electroconvulsive therapy (ECT) is the most effective antidepressant treatment. Biological predictors of clinical outcome to ECT are valuable. We aimed to examine multimodal magnetic resonance imaging (MRI) data that correlates to the efficacy of ECT. Structural and resting-state functional MRI data were acquired from 46 individuals (25 depressed individuals who received ECT, and 21 healthy controls). Whole-brain grey matter volume (GMV) and fractional amplitude of low frequency fluctuations (fALFF) were investigated to identify brain regions associated with post-ECT Hamilton Depression Rating Scale (HAM-D) total scores. GMV and fALFF values were compared with those in healthy controls using analysis of covariance (ANCOVA). Remission was defined by HAM-D ≤7. A multiple regression analysis revealed that pretreatment smaller GMV in the left thalamus was associated with worse response to ECT (i.e. higher post-ECT HAM-D). Pretreatment higher fALFF in the right anterior insula, and lower fALFF in the left thalamus and the cerebellum were associated with worse outcomes. The left thalamus was identified in both GMV and fALFF analyses. Nonremitters showed significantly smaller thalamic GMV compared to remitters and controls. We found that pretreatment thalamic volume and resting-state activity were associated with the efficacy of ECT. Our results highlight the importance of the thalamus as a possible biological predictor and its role in the underlying mechanisms of ECT action.

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Effectiveness and safety of long-term benzodiazepine use in anxiety disorders: a systematic review and meta-analysis

Shinfuku M., Kishimoto T., Uchida H., Suzuki T., Mimura M., Kikuchi T.

International clinical psychopharmacology （International clinical psychopharmacology） 34 （ 5 ） 211 - 221 2019年09月

Long-term benzodiazepines (BZDs) use is not endorsed in the treatment guidelines for anxiety disorders, but is prevalent in the real-world clinical settings. A systematic literature review was performed by using PubMed (last search: May 2019) to identify randomized controlled trials (RCTs) or maintenance studies following RCT that examined the effectiveness of BZDs in patients with anxiety disorders for a duration of 13 weeks or more. Meta-analyses were then conducted regarding changes in the Hamilton Anxiety Rating Scale (HAM-A) scores from baseline through endpoint, all-cause discontinuation, side effects, and the numbers of panic attacks at endpoint. Eight studies were identified (N = 1228). There were no significant differences in all outcomes between BZDs and antidepressants after the initial 8-week treatment. While no significant difference was noted in the HAM-A score changes between BZDs and placebo, BZDs resulted in a lower discontinuation rate and more frequent constipation and dry mouth than placebo. Our study indicates that for those who respond to an initial 8-week treatment, continuing BZDs is equivalent to antidepressants in efficacy and safety. However, the limited number of studies warranted further investigations of the long-term effectiveness and safety of BZDs.

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Long-Acting Injectables Versus Oral Antipsychotics: A Retrospective Bidirectional Mirror-Image Study

Miura G., Misawa F., Kawade Y., Fujii Y., Mimura M., Kishimoto T.

Journal of Clinical Psychopharmacology （Journal of Clinical Psychopharmacology） 39 （ 5 ） 441 - 445 2019年09月

ISSN 02710749

© Wolters Kluwer Health, Inc. All rights reserved. Purpose Mirror-image studies, which compare equal periods of time before and after a new treatment is introduced, may reflect the real-world impact of that treatment. However, most mirror-image studies that have investigated the impact of long-acting injectable antipsychotics (LAIs) were unidirectional in design, for patients switching from oral antipsychotics (OAPs) to LAIs. Therefore, we conducted a bidirectional mirror-image study comparing LAIs and OAPs. Methods We included 126 schizophrenia or schizoaffective disorder patients' LAI treatment data from 3 psychiatric hospitals. Patients took OAPs for 6 months or more before initiating LAIs, or the reverse. We obtained data on the number of hospitalizations as a primary outcome, plus the total duration and mean duration of hospitalization as secondary outcomes during the 6 months of the patients' first treatment, and the 6 months after the patients started their second type of treatment. Results The results indicated that there was no significant difference in any outcomes between LAI and OAP treatment when going from LAIs to OAPs (n = 59). However, when patients started with OAPs and switched to LAIs (n = 67), they were hospitalized a significantly fewer number of times, and the duration of their stays was shorter in the LAI phase than in the OAP phase. When combined with bidirectional data, LAI superiority was still observed. Conclusions The findings endorse the relative effectiveness of LAIs over OAPs in the real world, although the inherent flaws of mirror-image studies such as expectation bias and having no parallel comparator should be considered.

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Prolonged Post-Electroconvulsive Therapy Delirium Controlled With Donepezil

Takamiya A, Sawada K, Hirano J, Mimura M, Kishimoto T.

Journal of ECT 35 （ 3 ） E29 - E33 2019年09月

査読有り, ISSN 10950680

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Facial Landmark Activity Features for Depression Screening

Sumali B., Mitsukura Y., Tazawa Y., Kishimoto T.

2019 58th Annual Conference of the Society of Instrument and Control Engineers of Japan, SICE 2019 （2019 58th Annual Conference of the Society of Instrument and Control Engineers of Japan, SICE 2019） 1376 - 1381 2019年09月

© 2019 The Society of Instrument and Control Engineers - SICE. Depression is the most common mood disorder in the world which is also the leading cause of suicide. Depression might be diagnosed using varying modalities, as it affects many aspects of the patient, not only the patient will appear melancholic, but the patient's sleep quality and life quality might also be disrupted. In this study, we aim to extract facial landmark features unique to depression patients and build a machine learning model to classify the depression severity. The facial landmark activities considered in this study include: speed statistics of the landmarks, the standard deviation of eye pupils, and statistical features of mouth area. We found several facial landmark activity features with significant differences between healthy volunteers and depressed patients. We also successfully built machine learning models for automatic depression severity prediction.

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Psychiatrists' perceptions of medication adherence among patients with schizophrenia: An international survey.

59. Kurokawa S, Kishimoto T, Su KP, Chang JP, Chang HC, Yu X, Rodrigues-Silva N,Nielsen J, Unadkat A, Castle D, Haddad PM, Rocha D, Gadelha A, Kaliora S,Petrides G, Agid O, Tazawa Y, Takamiya A, Horigome T, Kane JM.

Schizophr Res 211 105 - 107 2019年09月

研究論文（学術雑誌）, 共著, 査読有り

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Effectiveness and safety of long term benzodiazepine use in anxiety disorders: a systematic review and meta-analysis.

Int Clin Psychopharmacol 34 （ 5 ） 211 - 221 2019年09月

研究論文（学術雑誌）, 査読有り

日本の大学生におけるインターネット使用と精神症状との関連, 精神神経学雑誌

9. 北沢桃子, 吉村道孝, 村田まゆ, 藤本友香, 一言英文, 三村　將, 坪田一男, 岸本泰士郎

精神神経学雑誌 121 （ 8 ） 593 - 601 2019年08月

研究論文（学術雑誌）, 共著, 査読有り

Corpus Analysis of Psychiatric Disorders Utilizing Natural Language Processing and Neurolinguistics

Kudo K., Kishimoto T.

Brain and nerve = Shinkei kenkyu no shinpo （Brain and nerve = Shinkei kenkyu no shinpo） 71 （ 7 ） 765 - 770 2019年07月

ISSN 18816096

Natural language processing (NLP) is a technology in which a computer processes human "natural language" directly. Along with the development of technologies such as automatic morphological analysis and transition words or sentences to vectors, more research that targets psychiatric disorders utilizing NLP is being conducted. In this manuscript, we will review some of these studies. Such approaches may resolve many problems regarding the assessment of psychiatric illnesses, and are expected to contribute to neurolinguistics.

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Switching to antipsychotic monotherapy vs. staying on antipsychotic polypharmacy in schizophrenia: A systematic review and meta-analysis

Matsui K., Tokumasu T., Takekita Y., Inada K., Kanazawa T., Kishimoto T., Takasu S., Tani H., Tarutani S., Hashimoto N., Yamada H., Yamanouchi Y., Takeuchi H.

Schizophrenia Research （Schizophrenia Research） 209 50 - 57 2019年07月

ISSN 09209964

© 2019 Elsevier B.V. Background: While recent meta-analyses have reported the superiority of antipsychotic polypharmacy (APP) over antipsychotic monotherapy (APM) in schizophrenia, switching to APM can be beneficial in terms of side effects. To determine whether patients receiving APP should switch to APM or stay on APP, we conducted a systematic review and meta-analysis. Methods: Randomized controlled trials (RCTs) examining a switch from APP to APM vs. staying on APP were systematically selected from a previous meta-analysis comparing APP with APM in patients with schizophrenia. In addition, we conducted an updated systematic literature search using MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. Data on study discontinuation, relapse, psychopathology, neurocognition, extrapyramidal symptoms, and body weight/body mass index (BMI) were extracted and synthesized. Results: A total of 6 RCTs involving 341 patients were included. All studies examined a switch from 2 antipsychotic agents to a single agent. Clozapine-treated patients were included in 3 studies. There was a significant difference in study discontinuation due to all causes in favor of staying on APP (N = 6, n = 341, RR = 2.28, 95% CI = 1.50–3.46, P < 0.001). There were no significant differences in relapse, any psychopathology, neurocognition, extrapyramidal symptoms, or body weight/BMI between the 2 groups. The quality of evidence was low to very low. Conclusions: The findings suggest that clinicians should closely monitor patient condition when switching to APM after receiving 2 antipsychotics. Given the low to very low overall quality of the evidence, the findings should be considered preliminary and inconclusive.

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Actigraphy for evaluation of mood disorders: A systematic review and meta-analysis

Tazawa Y., Wada M., Mitsukura Y., Takamiya A., Kitazawa M., Yoshimura M., Mimura M., Kishimoto T.

Journal of Affective Disorders （Journal of Affective Disorders） 253 257 - 269 2019年06月

ISSN 01650327

© 2019 Background: Actigraphy has enabled consecutive observation of individual health conditions such as sleep or daily activity. This study aimed to examine the usefulness of actigraphy in evaluating depressive and/or bipolar disorder symptoms. Method: A systematic review and meta-analysis was conducted. We selected studies that used actigraphy to compare either patients vs. healthy controls, or pre- vs. post-treatment data from the same patient group. Common actigraphy measurements, namely daily activity and sleep-related data, were extracted and synthesized. Results: Thirty-eight studies (n = 3,758) were included in the analysis. Compared with healthy controls, depressive patients were less active (standardized mean difference; SMD=1.27, 95%CI=[0.97, 1.57], P<0.001) and had longer wake after sleep onset (SMD= − 0.729, 95%CI=[− 1.20, − 0.25], p = 0.003). Total sleep time (SMD= − 0.33, 95%CI=[− 0.55, − 0.11], P = 0.004), sleep latency (SMD= − 0.22, 95%CI=[− 0.42, − 0.02], P = 0.032), and wake after sleep onset (SMD= − 0.22, 95%CI=[− 0.39, − 0.04], P = 0.015) were longer in euthymic/remitted patients compared to healthy controls. In pre- and post-treatment comparisons, sleep latency (SMD=− 0.85, 95%CI=[− 1.53, − 0.17], P = 0.015), wake after sleep onset (SMD= − 0.65, 95%CI=[− 1.20, − 0.10], P = 0.022), and sleep efficiency (SMD=0.77, 95%CI=[0.29, 1.24], P = 0.002) showed significant improvement. Limitation: The sample sizes for each outcome were small. The type of actigraphy devices and patients’ illness severity differed across studies. It is possible that hospitalizations and medication influenced the outcomes. Conclusion: We found significant differences between healthy controls and mood disorders patients for some actigraphy-measured modalities. Specific measurement patterns characterizing each mood disorder/status were also found. Additional actigraphy data linked to severity and/or treatment could enhance the clinical utility of actigraphy.

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IN VIVO RETENTION PATTERNS OF 18F‐PI‐2620 IN DIVERSE TAUOPATHIES, AND ASSESSMENTS OF THOSE RESEMBLANCE TO PATHOGNOMONIC DISTRIBUTION OF TAU DEPOSITS.

Yamamoto Y, Takahata K, Tezuka T, Sano Y, Kurokawa S, Kurose S, Mizushima J, Mashima K, Okada K, Seki M, Yamagata B, Yoshizaki T, Kishimoto T, Nakahara T, Tabuchi H, Ito D, Jinzaki M, Mimura M.

Alzheimer's Association International Conference 2019 15 （ 7S ） 1085 2019年06月

研究論文（国際会議プロシーディングス）, 共著

LINICAL CHARACTERIZATION OF 18F‐PI2620 IN ALZHEIMER'S DISEASE AND OTHER TAUOPATHIES.

Sano Y, Takahata K, Yamamoto Y, Tezuka T, Kurose S, Kurokawa S, Mizushima J, Mashima K, Okada K, Seki M, Yamagata B, Yoshizaki T, Kishimoto T, Nakahara T, Ito D, Tabuchi H, Jinzaki M, Mimura M.

Alzheimer's Association International Conference 2019 15 （ 7S ） 1093 - 1094 2019年06月

研究論文（国際会議プロシーディングス）, 共著

Structural Magnetic Resonance Imaging for Individual Predictions for Electroconvulsive Therapy Remission Utilizing Machine Learning

Takamiya Akihiro, Liang Kuo-ching, Nishikata Shiro, Kurokawa Shunya, Sawada Kyosuke, Hirano Jinichi, Yamagata Bun, Mimura Masaru, Kishimoto Taishiro

BIOLOGICAL PSYCHIATRY 85 （ 10 ） S263 - S263 2019年05月

ISSN 0006-3223

Electroconvulsive therapy modulates resting-state EEG oscillatory pattern and phase synchronization in nodes of the default mode network in patients with depressive disorder

Takamiya A., Hirano J., Yamagata B., Takei S., Kishimoto T., Mimura M.

Frontiers in Human Neuroscience （Frontiers in Human Neuroscience） 13 1 2019年02月

ISSN 1662-5161

© 2019 Takamiya, Hirano, Yamagata, Takei, Kishimoto and Mimura. Introduction: Electroconvulsive therapy (ECT) has antidepressant effects, but it also has possible cognitive side effects. The effects of ECT on neuronal oscillatory pattern and phase synchronization, and the relationship between clinical response or cognitive change and electroencephalogram (EEG) measurements remain elusive. Methods: Individuals with unipolar depressive disorder receiving bilateral ECT were recruited. Five minutes of resting, eyes-closed, 19-lead EEG recordings were obtained before and after a course of ECT. Non-overlapping 60 artifact-free epocs of 2-s duration were used for the analyses. We used exact low resolution electromagnetic tomography (eLORETA) to compute the whole-brain three-dimensional intracortical distribution of current source density (CSD) and phase synchronization among 28 regions-of-interest (ROIs). Paired t-tests were used to identify cortical voxels and connectivities showing changes after ECT. Montgomery Asberg Depression Rating Scale (MADRS) and Mini-Mental State Examination (MMSE) were used to evaluate the severity of depression and the global cognitive function. Correlation analyses were conducted to identify the relationship between changes in the EEG measurements and changes in MADRS or MMSE. Results: Thirteen depressed patients (five females, mean age: 58.4 years old) were included. ECT increased theta CSD in the anterior cingulate cortex (ACC), and decreased beta CSD in the frontal pole (FP), and gamma CSD in the inferior parietal lobule (IPL). ECT increased theta phase synchronization between the posterior cingulate cortex (PCC) and the anterior frontal cortex, and decreased beta phase synchronization between the PCC and temporal regions. A decline in beta synchronization in the left hemisphere was associated with cognitive changes after ECT. Conclusion: ECT modulated resting-state EEG oscillatory patterns and phase synchronization in central nodes of the default mode network (DMN). Changes in beta synchronization in the left hemisphere might explain the ECT-related cognitive side effects.

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Attitudes Toward Electroconvulsive Therapy among Involuntary and Voluntary Patients

岸本泰士郎

Journal of ECT （Journal of ECT） 35 （ 3 ） 165 - 169 2019年01月

研究論文（学術雑誌）, 査読有り, ISSN 10950680

© Wolters Kluwer Health, Inc. All rights reserved. Objective We aimed to examine attitudes toward electroconvulsive therapy (ECT) among involuntary patients, voluntary patients, and their relatives. Methods Patients experiencing a major depressive episode and receiving ECT and their relatives were recruited for the survey. Patients and their relatives answered the self-rating questionnaires with a 7-point Likert scale. We explored differences in the survey results between involuntary and voluntary patients, as well as differences in the survey results between patients and their relatives. Results We recruited 97 participants (53 patients and 44 relatives) for the survey. Approximately 80% of the patients showed positive attitudes toward ECT. There were no statistically significant differences between involuntary (n = 23) and voluntary (n = 30) patients across multiple aspects of the ECT experience, including treatment satisfaction, positive or adverse effects of ECT, and treatment preference in the future. Relatives were more satisfied with the positive effects of ECT and with the information offered before ECT treatment than the patients themselves. Conclusions Approximately 80% of the patients showed overall satisfaction with ECT irrespective of consent status. Relatives were more satisfied with ECT than patients. Electroconvulsive therapy can be a lifesaving treatment for severely depressed patients, and the subjective experience of involuntary patients should be taken into consideration when discussing involuntary ECT treatment.

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Acute and long-term effects of electroconvulsive therapy on human dentate gyrus

岸本泰士郎

Neuropsychopharmacology （Neuropsychopharmacology） 44 （ 10 ） 1805 - 1811 2019年01月

研究論文（学術雑誌）, 査読有り, ISSN 0893133X

© 2019, American College of Neuropsychopharmacology. Electroconvulsive therapy (ECT) is the most effective treatment for severe depression, although the underlying mechanisms remain unclear. Animal studies have consistently shown that electroconvulsive stimulation induces neuroplastic changes in the dentate gyrus. To date, few studies have investigated the effect of ECT on human hippocampal subfields. In the current study, structural magnetic resonance imaging (MRI) was conducted in 25 patients with major depressive episodes at 3 time points: before ECT (TP1), after 1 week of the last ECT (TP2) and after 3 months of the last ECT (TP3). Twenty healthy controls were scanned twice with an interval similar to patients between TP1 and TP2. Volumetric analyses of the cornu ammonis (CA)4/dentate gyrus (DG) were performed using the MAGeT-Brain (Multiple Automatically Generated Templates) algorithm. Clinically remitted patients after ECT showed larger volume increases in the right CA4/DG than non-remitted patients. Volume increases in the right CA4/DG were negatively associated with age. Increased CA4/DG volumes after ECT returned to baseline levels after 3 months irrespective of clinical state. ECT-induced volume increase in the CA4/DG was associated with age and clinical remission. These findings are consistent with the neurotrophic processes seen in preclinical studies. Neuroplastic change in the CA4/DG might mediate some of the short-term antidepressant effects of ECT.

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Artificial Intelligence in Psychiatry

Takamiya A., Tazawa Y., Kudo K., Kishimoto T.

Brain and nerve = Shinkei kenkyu no shinpo （Brain and nerve = Shinkei kenkyu no shinpo） 71 （ 1 ） 15 - 23 2019年01月

ISSN 18816096

Diagnosis of psychiatric disorders is based primarily on subjective symptoms, and neuroimaging or other biological examinations are used for excluding organic disorders. Advances in artificial intelligence technologies, such as machine learning, may enable us to utilize neuroimaging for individual diagnosis of psychiatric disorder or treatment response prediction. In addition, such technologies may elucidate the underlying pathophysiology of psychiatric disorders. In this article, we review studies that utilized machine learning on structural magnetic resonance imaging for depression.

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Actiraphy for Evaluation of Mood Disorders:A systemativc review and Meta-analysis.

Tazawa Y, Wada M, Mitsukura Y, Takamiya A, Kitazawa M, Yoshimura M, Mimura M, Kishimoto T.

（J Affect Disord. 2019 (in press)） 2019年

査読有り

Remote neuropsychological assessment of elderly Japanese population using the Alzheimer’s Disease Assessment Scale: A validation study

Yoshida K., Yamaoka Y., Eguchi Y., Sato D., Iiboshi K., Kishimoto M., Mimura M., Kishimoto T.

J Telemed Telecare 2019 (in press) （Journal of Telemedicine and Telecare） 26 （ 7-8 ） 1357633X19845278 - 487 2019年

査読有り, ISSN 1357633X

© The Author(s) 2019. Introduction: Studies have demonstrated the high agreement of several remote neuropsychological tests using video teleconferencing (VTC) with face-to-face (FTF) tests. However, the reliability of the remotely administered Alzheimer’s Disease Assessment Scale cognitive subscale (ADAS-cog), one of the most commonly used neuropsychological tests to detect cognitive decline, has not been substantially elucidated, particularly in Japanese populations. Therefore, this study aimed to evaluate the reliability of the remotely administered ADAS-cog compared with FTF-administered ADAS-cog among elderly Japanese participants. Methods: Participants aged ≥60 years with and without cognitive impairment, i.e. those with mild cognitive impairment (MCI), those with dementia and healthy controls (HCs), were assessed with the ADAS-cog using VTC and FTF testing at an interval of >2 weeks and <3 months. The assessment order (VTC or FTF) was randomized by participants. Participants’ scores were compared among the entire sample, as well as subgroups, using intra-class correlation coefficients (ICCs) in a mixed-effects model. Results: A total of 73 participants were included in the study (36 men; age, 76.3 ± 7.6 years). The ICC for the ADAS-cog total score was high in the entire sample (0.86), whereas ICCs were moderate to high for the subgroups (MCI: 0.63, dementia: 0.80 and HC: 0.74). Discussion: The results indicate that a VTC-administered ADAS-cog could be an alternative for an FTF-administered ADAS-cog, although further replication studies with larger sample sizes and a wider range of cognitive functionalities are warranted.

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Long-term effectiveness of oral second-generation antipsychotics in patients with schizophrenia and related disorders: a systematic review and meta-analysis of direct head-to-head comparisons

Kishimoto T., Hagi K., Nitta M., Kane J., Correll C.

World Psychiatry 2019 (in press) （World Psychiatry） 18 （ 2 ） 208 - 224 2019年

査読有り, ISSN 17238617

© 2019 World Psychiatric Association Second-generation antipsychotics (SGAs) are recommended for maintenance treatment in schizophrenia. However, comparative long-term effectiveness among SGAs is unclear. Here we provide a systematic review and meta-analysis of randomized trials lasting ≥⃒6 months comparing SGAs head-to-head in schizophrenia and related disorders. The primary outcome was all-cause discontinuation. Secondary outcomes included efficacy and tolerability, i.e., psychopathology, inefficacy-related and intolerability-related discontinuation, relapse, hospitalization, remission, functioning, quality of life, and adverse events. Pooled risk ratio and standardized mean difference were calculated using random-effects models. Across 59 studies (N=45,787), lasting 47.4±32.1 weeks (range 24-186), no consistent superiority of any SGA emerged across efficacy and tolerability outcomes. Regarding all-cause discontinuation, clozapine, olanzapine and risperidone were significantly (p<0.05) superior to several other SGAs, while quetiapine was inferior to several other SGAs. As to psychopathology, clozapine and olanzapine were superior to several other SGAs, while quetiapine and ziprasidone were inferior to several other SGAs. Data for other efficacy outcomes were sparse. Regarding intolerability-related discontinuation, risperidone was superior and clozapine was inferior to several other SGAs. Concerning weight gain, olanzapine was worse than all other compared non-clozapine SGAs, and risperidone was significantly worse than several other SGAs. As to prolactin increase, risperidone and amisulpride were significantly worse than several other SGAs. Regarding parkinsonism, olanzapine was superior to risperidone, without significant differences pertaining to akathisia. Concerning sedation and somnolence, clozapine and quetiapine were significantly worse than some other SGAs. In summary, different long-term SGA efficacy and tolerability patterns emerged. The long-term risk-benefit profiles of specific SGAs need to be tailored to individual patients to optimize maintenance treatment outcomes.

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Improvement of psychiatrists’ clinical knowledge of the treatment guidelines for schizophrenia and major depressive disorders using the ‘Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE)’ project: A nationwide dissemination, education, and evaluation study

Takaesu Y., Watanabe K., Numata S., Iwata M., Kudo N., Oishi S., Takizawa T., Nemoto K., Yasuda Y., Tagata H., Tsuboi T., Tsujino N., Hashimoto N., Matsui Y., Hori H., Yamamori H., Sugiyama N., Suwa T., Kishimoto T., Hishimoto A., Usami M., Furihata R., Iwamoto K., Fujishiro H., Nakamura T., Mizuno K., Inagaki T., Katsumoto E., Tomita H., Ohi K., Muraoka H., Atake K., Iida H., Nagasawa T., Fujita J., Yamamura S., Onitsuka T., Murata A., Takayanagi Y., Noda H., Matsumura Y., Takezawa K., Iga J., Ichihashi K., Ogasawara K., Yamada H., Inada K., Hashimoto R.

Psychiatry and Clinical Neurosciences （Psychiatry and Clinical Neurosciences） 73 （ 10 ） 642 - 648 2019年

ISSN 13231316

© 2019 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology Aim: Although treatment guidelines for pharmacological therapy for schizophrenia and major depressive disorder have been issued by the Japanese Societies of Neuropsychopharmacology and Mood Disorders, these guidelines have not been well applied by psychiatrists throughout the nation. To address this issue, we developed the ‘Effectiveness of Guidelines for Dissemination and Education in Psychiatric Treatment (EGUIDE)’ integrated education programs for psychiatrists to disseminate the clinical guidelines. Additionally, we conducted a systematic efficacy evaluation of the programs. Methods: Four hundred thirteen out of 461 psychiatrists attended two 1-day educational programs based on the treatment guidelines for schizophrenia and major depressive disorder from October 2016 to March 2018. We measured the participants’ clinical knowledge of the treatment guidelines using self-completed questionnaires administered before and after the program to assess the effectiveness of the programs for improving knowledge. We also examined the relation between the participants’ demographics and their clinical knowledge scores. Results: The clinical knowledge scores for both guidelines were significantly improved after the program. There was no correlation between clinical knowledge and participant demographics for the program on schizophrenia; however, a weak positive correlation was found between clinical knowledge and the years of professional experience for the program on major depressive disorder. Conclusion: Our results provide evidence that educational programs on the clinical practices recommended in guidelines for schizophrenia and major depressive disorder might effectively improve participants’ clinical knowledge of the guidelines. These data are encouraging to facilitate the standardization of clinical practices for psychiatric disorders.

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Brain Changes Induced by Electroconvulsive Therapy Are Broadly Distributed

Ousdal O., Argyelan M., Narr K., Abbott C., Wade B., Vandenbulcke M., Urretavizcaya M., Tendolkar I., Takamiya A., Stek M., Soriano-Mas C., Redlich R., Paulson O., Oudega M., Opel N., Nordanskog P., Kishimoto T., Kampe R., Jorgensen A., Hanson L., Hamilton J., Espinoza R., Emsell L., van Eijndhoven P., Dols A., Dannlowski U., Cardoner N., Bouckaert F., Anand A., Bartsch H., Kessler U., Oedegaard K., Dale A., Oltedal L., Erchinger V., Haavik J., Evjenth Sørhaug O., Jørgensen M., Bolwig T., Magnusson P., Cano M., Pujol J., Menchón J., Petrides G., Sienaert P.

Biological Psychiatry （Biological Psychiatry） 87 （ 5 ） 451 - 461 2019年

ISSN 00063223

© 2019 Society of Biological Psychiatry Background: Electroconvulsive therapy (ECT) is associated with volumetric enlargements of corticolimbic brain regions. However, the pattern of whole-brain structural alterations following ECT remains unresolved. Here, we examined the longitudinal effects of ECT on global and local variations in gray matter, white matter, and ventricle volumes in patients with major depressive disorder as well as predictors of ECT-related clinical response. Methods: Longitudinal magnetic resonance imaging and clinical data from the Global ECT-MRI Research Collaboration (GEMRIC) were used to investigate changes in white matter, gray matter, and ventricle volumes before and after ECT in 328 patients experiencing a major depressive episode. In addition, 95 nondepressed control subjects were scanned twice. We performed a mega-analysis of single subject data from 14 independent GEMRIC sites. Results: Volumetric increases occurred in 79 of 84 gray matter regions of interest. In total, the cortical volume increased by mean ± SD of 1.04 ± 1.03% (Cohen's d = 1.01, p < .001) and the subcortical gray matter volume increased by 1.47 ± 1.05% (d = 1.40, p < .001) in patients. The subcortical gray matter increase was negatively associated with total ventricle volume (Spearman's rank correlation ρ = −.44, p < .001), while total white matter volume remained unchanged (d = −0.05, p = .41). The changes were modulated by number of ECTs and mode of electrode placements. However, the gray matter volumetric enlargements were not associated with clinical outcome. Conclusions: The findings suggest that ECT induces gray matter volumetric increases that are broadly distributed. However, gross volumetric increases of specific anatomically defined regions may not serve as feasible biomarkers of clinical response.

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Simple Stress Quantitative Evalution for Healthcare Using Daily KANSEI Detection with EEG Device - Relation between Stress and Healthcare

Mitsukura Y., Sumali B., Tazawa Y., Kishimoto T., and Mimura M

Modern Environmental Science and Engineering 5 （ 5 ） 345 - 350 2019年

研究論文（学術雑誌）, 査読有り

The project for objective measures using computational psychiatry technology (PROMPT): Rationale, design, and methodology

Kishimoto T., Takamiya A., Liang K.c., Funaki K., Fujita T., Kitazawa M., Yoshimura M., Tazawa Y., Horigome T., Eguchi Y., Kikuchi T., Tomita M., Bun S., Murakami J., Sumali B., Warnita T., Kishi A., Yotsui M., Toyoshiba H., Mitsukura Y., Shinoda K., Sakakibara Y., Mimura M.

Contemporary Clinical Trials Communications （Contemporary Clinical Trials Communications） 19 100649 2019年

研究論文（学術雑誌）, 査読有り, ISSN 24518654

© 2020 The Authors Introduction: Depressive and neurocognitive disorders are debilitating conditions that account for the leading causes of years lived with disability worldwide. However, there are no biomarkers that are objective or easy-to-obtain in daily clinical practice, which leads to difficulties in assessing treatment response and developing new drugs. New technology allows quantification of features that clinicians perceive as reflective of disorder severity, such as facial expressions, phonic/speech information, body motion, daily activity, and sleep. Methods: Major depressive disorder, bipolar disorder, and major and minor neurocognitive disorders as well as healthy controls are recruited for the study. A psychiatrist/psychologist conducts conversational 10-min interviews with participants ≤10 times within up to five years of follow-up. Interviews are recorded using RGB and infrared cameras, and an array microphone. As an option, participants are asked to wear wrist-band type devices during the observational period. Various software is used to process the raw video, voice, infrared, and wearable device data. A machine learning approach is used to predict the presence of symptoms, severity, and the improvement/deterioration of symptoms. Discussion: The overall goal of this proposed study, the Project for Objective Measures Using Computational Psychiatry Technology (PROMPT), is to develop objective, noninvasive, and easy-to-use biomarkers for assessing the severity of depressive and neurocognitive disorders in the hopes of guiding decision-making in clinical settings as well as reducing the risk of clinical trial failure. Challenges may include the large variability of samples, which makes it difficult to extract the features that commonly reflect disorder severity. Trial Registration: UMIN000021396, University Hospital Medical Information Network (UMIN).

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腸内細菌と自閉症スペクトラム障害

黒川駿哉, 岸本泰士郎, 真田健史, 三村將

日本生物学的精神医学会誌（日本生物学的精神医学会） 30 （ 2 ） 55 - 59 2019年

ISSN 2186-6619

腸内細菌叢とその代謝産物が，腸を介して脳に作用し，相互に影響し合うという腸内フローラ‐腸‐脳軸（microbiota‐gut‐brain axis）が注目されている。自閉症スペクトラム障害（autism spectrum disorder：ASD）は精神神経科領域において，microbiota‐gut‐brain axisについての報告が最も多い疾患の一つである。健常と比べてASDでは特定の菌種・構成パターンの違いや多様性の乱れ（dysbiosis）が報告されている一方で，このdysbiosisを復する目的で，腸内細菌叢移植（fecal microbiota transplantation：FMT）などの新しい試みについての報告も出てきている。本稿では，最新の腸内細菌叢の観察研究および介入研究について紹介し，治療応用や病態理解の可能性など今後の展望について述べる。

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腸内細菌と自閉症スペクトラム障害

黒川駿哉, 岸本泰士郎, 真田健史, 三村將

日本生物学的精神医学会誌（日本生物学的精神医学会） 30 （ 2 ） 55 - 59 2019年

ISSN 2186-6619

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Internet-Based Cognitive Behavioral Therapy With Real-Time Therapist Support via Videoconference for Patients With Obsessive-Compulsive Disorder, Panic Disorder, and Social Anxiety Disorder: Pilot Single-Arm Trial

Matsumoto K., Sutoh C., Asano K., Seki Y., Urao Y., Yokoo M., Takanashi R., Yoshida T., Tanaka M., Noguchi R., Nagata S., Oshiro K., Numata N., Hirose M., Yoshimura K., Nagai K., Sato Y., Kishimoto T., Nakagawa A., Shimizu E.

Journal of medical Internet research （Journal of medical Internet research） 20 （ 12 ） e12091 2018年12月

ISSN 1438-8871

©Kazuki Matsumoto, Chihiro Sutoh, Kenichi Asano, Yoichi Seki, Yuko Urao, Mizue Yokoo, Rieko Takanashi, Tokiko Yoshida, Mari Tanaka, Remi Noguchi, Shinobu Nagata, Keiko Oshiro, Noriko Numata, Motohisa Hirose, Kensuke Yoshimura, Kazue Nagai, Yasunori Sato, Taishiro Kishimoto, Akiko Nakagawa, Eiji Shimizu. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 17.12 BACKGROUND: Cognitive behavioral therapy (CBT) is the first-line treatment for adults with obsessive-compulsive disorder (OCD), panic disorder (PD), and social anxiety disorder (SAD). Patients in rural areas can access CBT via the internet. The effectiveness of internet-delivered cognitive behavioral therapy (ICBT) has been consistently shown, but no clinical studies have demonstrated the feasibility of ICBT with real-time therapist support via videoconference for OCD, PD, and SAD at the same time. OBJECTIVES: This study aimed to evaluate the feasibility of videoconference-delivered CBT for patients with OCD, PD, or SAD. METHODS: A total of 30 Japanese participants (mean age 35.4 years, SD 9.2) with OCD, SAD, or PD received 16 sessions of individualized videoconference-delivered CBT with real-time support of a therapist, using tablet personal computer (Apple iPad Mini 2). Treatment involved individualized CBT formulations specific to the presenting diagnosis; all sessions were provided by the same therapist. The primary outcomes were reduction in symptomatology, using the Yale-Brown obsessive-compulsive scale (Y-BOCS) for OCD, Panic Disorder Severity Scale (PDSS) for PD, and Liebowitz Social Anxiety Scale (LSAS) for SAD. The secondary outcomes included the EuroQol-5 Dimension (EQ-5D) for Quality of Life, the Patient Health Questionnaire (PHQ-9) for depression, the Generalized Anxiety Disorder (GAD-7) questionnaire for anxiety, and Working Alliance Inventory-Short Form (WAI-SF). All primary outcomes were assessed at baseline and at weeks 1 (baseline), 8 (midintervention), and 16 (postintervention) face-to-face during therapy. The occurrence of adverse events was observed after each session. For the primary analysis comparing between pre- and posttreatments, the participants' points and 95% CIs were estimated by the paired t tests with the change between pre- and posttreatment. RESULTS: A significant reduction in symptom of obsession-compulsion (Y-BOCS=-6.2; Cohen d=0.74; 95% CI -9.4 to -3.0, P=.002), panic (PDSS=-5.6; Cohen d=0.89; 95% CI -9.83 to -1.37; P=.02), social anxiety (LSAS=-33.6; Cohen d=1.10; 95% CI -59.62 to -7.49, P=.02) were observed. In addition, depression (PHQ-9=-1.72; Cohen d=0.27; 95% CI -3.26 to -0.19; P=.03) and general anxiety (GAD-7=-3.03; Cohen d=0.61; 95% CI -4.57 to -1.49, P<.001) were significantly improved. Although there were no significant changes at 16 weeks from baseline in EQ-5D (0.0336; Cohen d=-0.202; 95% CI -0.0198 to 0.00869; P=.21), there were high therapeutic alliance (ie, WAI-SF) scores (from 68.0 to 73.7) throughout treatment, which significantly increased (4.14; 95% CI 1.24 to 7.04; P=.007). Of the participants, 86% (25/29) were satisfied with videoconference-delivered CBT, and 83% (24/29) preferred videoconference-delivered CBT to face-to-face CBT. An adverse event occurred to a patient with SAD; the incidence was 3% (1/30). CONCLUSIONS: Videoconference-delivered CBT for patients with OCD, SAD, and SAD may be feasible and acceptable.

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Sleep disorders are a prevalent and serious comorbidity in dry eye

岸本泰士郎

Investigative Ophthalmology and Visual Science （Investigative Ophthalmology and Visual Science） 59 （ 14 ） DES143 - DES150 2018年11月

研究論文（学術雑誌）, ISSN 01460404

© 2018 The Authors. PURPOSE. Sleep is an essential life habit and closely associated with lifespan, diabetes, hypertension, and mental health. Sleep disorders are a prominent, but overlooked problem in patients with dry eye disease (DED), characterized by a poor sleep index, short sleep duration, long sleep latency, and poor subjective sleep. DED and sleep disorders are more prevalent in women than men. Moreover, sleep quality in DED is worse than in other eye diseases, including glaucoma, retinal diseases, cataract, and allergic and chronic conjunctivitis. METHODS. We reviewed the literature for studies investigating sleep and health, eyes and sleep, and DED and sleep, in terms of systemic and eye health, especially in women. RESULTS. Two studies reported that approximately half of patients with DED suffer from poor sleep. The severity of mood disorders, including anxiety and depression, is correlated strongly with sleep disorders in DED, and the symptoms and signs of DED, especially pain, also are correlated with sleep quality. Sleep disorders are documented in primary Sjögren’s syndrome and an association with sleep apnea and depression is suggested. Primary Sjögren’s syndrome includes arthritis and other rheumatic disease causing pain and fatigue; however, how sicca contributes to sleep disorders is not known. CONCLUSIONS. Possible explanations for sleep disorders in DED may be depression, pain, and eye exposure at night. Reciprocal effects may be expected and consultation-liaison psychiatry is recommended for the management of sleep disorders in DED. Topical medication and lid heating also may be advantageous for sleep quality in DED.

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Minocycline as a treatment for schizophrenia:is the discussion truly finished?

岸本泰士郎

Lancet Psychiatry 5 （ 11 ） 856 - 857 2018年11月

研究論文（学術雑誌）, 査読有り

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Utilization of Facial Image Analysis Technology for Blink Detection: A Validation Study

Kitazawa M., Yoshimura M., Liang K., Wada S., Mimura M., Tsubota K., Kishimoto T.

Eye & contact lens （Eye & contact lens） 44 （ Suppl 2 ） S297 - S301 2018年11月

研究論文（学術雑誌）, 査読有り, ISSN 1542-2321

PURPOSE: The assessment of anterior eye diseases and the understanding of psychological functions of blinking can benefit greatly from a validated blinking detection technology. In this work, we proposed an algorithm based on facial recognition built on current video processing technologies to automatically filter and analyze blinking movements. We compared electrooculography (EOG), the gold standard of blinking measurement, with manual video tape recording counting (mVTRc) and our proposed automated video tape recording analysis (aVTRa) in both static and dynamic conditions to validate our aVTRa method. METHODS: We measured blinking in both static condition, where the subject was sitting still with chin fixed on the table, and dynamic condition, where the subject's face was not fixed and natural communication was taking place between the subject and interviewer. We defined concordance of blinks between measurement methods as having less than 50 ms difference between eyes opening and closing. RESULTS: The subjects consisted of seven healthy Japanese volunteers (3 male, four female) without significant eye disease with average age of 31.4±7.2. The concordance of EOG vs. aVTRa, EOG vs. mVTRc, and aVTRa vs. mVTRc (average±SD) were found to be 92.2±10.8%, 85.0±16.5%, and 99.6±1.0% in static conditions and 32.6±31.0%, 28.0±24.2%, and 98.5±2.7% in dynamic conditions, respectively. CONCLUSIONS: In static conditions, we have found a high blink concordance rate between the proposed aVTRa versus EOG, and confirmed the validity of aVTRa in both static and dynamic conditions.

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The relationship of dry eye disease with depression and anxiety: A naturalistic observational study

Kitazawa M., Sakamoto C., Yoshimura M., Kawashima M., Inoue S., Mimura M., Tsubota K., Negishi K., Kishimoto T.

Translational Vision Science and Technology （Translational Vision Science and Technology） 7 （ 6 ） 35 2018年11月

ISSN 2164-2591

© 2018 The Authors. Purpose: In recent years, the relationship between dry eye disease (DED) and psychiatric disorders has been gaining attention. The relationship between dry eye symptoms and psychiatric symptoms has been reported in multiple retrospective studies. However, in previous studies there have been limitations to these observations, such as a lack of close examination of either DED or mood symptoms. Methods: In this study, we evaluated the psychological state and social functionality of DED patients by administering validated psychiatric tests as well as ophthalmologic examinations twice during the course of DED treatment. Forty subjects (61.3 ± 18.1-years old) received the primary psychiatric assessments and 26 received the secondary psychiatric assessments. Results: In a cross-sectional examination, we found patients with depressive and/or anxiety symptoms had higher Dry Eye Related Quality of Life Score (DEQ) scores, whereas the objective symptoms of DED did not differ between groups. We also found a positive relationship between depression/anxiety scores and DED subjective symptoms. On the other hand, in longitudinal examination, we found psychiatric symptoms had no impact on subjective and objective DED symptoms throughout the course of DED symptoms. Conclusions: We found depression and anxiety were related to the subjective symptoms of DED but not the objective symptoms. Translational Relevance: It is important to pay attention to psychiatric symptoms in patients with DED and an investigation into appropriate treatment strategies for patients with DED in combination with psychiatric symptoms is needed in the future.

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Glutamatergic neurometabolite levels in major depressive disorder: a systematic review and meta-analysis of proton magnetic resonance spectroscopy studies

岸本泰士郎

Molecular Psychiatry （Molecular Psychiatry） 24 （ 7 ） 952 - 964 2018年10月

研究論文（学術雑誌）, ISSN 13594184

© 2018, The Author(s). Alterations in glutamatergic neurotransmission are implicated in the pathophysiology of depression, and the glutamatergic system represents a treatment target for depression. To summarize the nature of glutamatergic alterations in patients with depression, we conducted a meta-analysis of proton magnetic resonance (1H-MRS) spectroscopy studies examining levels of glutamate. We used the search terms: depress* AND (MRS OR “magnetic resonance spectroscopy”). The search was performed with MEDLINE, Embase, and PsycINFO. The inclusion criteria were 1H-MRS studies comparing levels of glutamate + glutamine (Glx), glutamate, or glutamine between patients with depression and healthy controls. Standardized mean differences (SMD) were calculated to assess group differences in the levels of glutamatergic neurometabolites. Forty-nine studies met the eligibility criteria, which included 1180 patients and 1066 healthy controls. There were significant decreases in Glx within the medial frontal cortex (SMD = −0.38; 95% CI, −0.69 to −0.07) in patients with depression compared with controls. Subanalyses revealed that there was a significant decrease in Glx in the medial frontal cortex in medicated patients with depression (SMD = −0.50; 95% CI, −0.80 to −0.20), but not in unmedicated patients (SMD = −0.27; 95% CI, −0.76 to 0.21) compared with controls. Overall, decreased levels of glutamatergic metabolites in the medial frontal cortex are linked with the pathophysiology of depression. These findings are in line with the hypothesis that depression may be associated with abnormal glutamatergic neurotransmission.

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Non-consenting and Consenting Patients' satisfaction after Electroconvulsive Therapy

Takamiya Akihiro, Sawada Kyosuke, Mimura Masaru, Kishimoto Taishiro

JOURNAL OF ECT 34 （ 3 ） 205 - 205 2018年09月

ISSN 1095-0680

The effect of fecal microbiota transplantation on psychiatric symptoms among patients with irritable bowel syndrome, functional diarrhea and functional constipation: An open-label observational study

Kurokawa S., Kishimoto T., Mizuno S., Masaoka T., Naganuma M., Liang K., Kitazawa M., Nakashima M., Shindo C., Suda W., Hattori M., Kanai T., Mimura M.

Journal of Affective Disorders （Journal of Affective Disorders） 235 506 - 512 2018年08月

研究論文（学術雑誌）, ISSN 01650327

© 2018 Elsevier B.V. Backgrounds: The intestinal microbiota is considered as a potential common underpinning pathophysiology of Functional Gastrointestinal Disorders (FGIDs) and psychiatric disorders such as depression and anxiety. Fecal Microbiota Transplantation (FMT) has been reported to have therapeutic effects on diseases related to dysbiosis, but few studies have evaluated its effect on psychiatric symptoms. Methods: We followed 17 patients with either Irritable Bowel Syndrome (IBS), Functional Diarrhea (FDr) or Functional Constipation (FC) who underwent FMT for the treatment of gastrointestinal symptoms and observation of psychiatric symptoms. Changes in Hamilton Rating Scale for Depression (HAM-D) and subscale of sleep-related items, Hamilton Rating Scale for Anxiety (HAM-A) and Quick Inventory for Depressive Symptoms (QIDS) between baseline and 4 weeks after FMT, and relationship with the intestinal microbiota were measured. Results: At baseline, 12 out of 17 patients were rated with HAM-D ≥ 8. Significant improvement in HAM-D total and sleep subscale score, HAM-A and QIDS were observed (p = 0.007, p = 0.007, p = 0.01, p = 0.007, respectively). Baseline Shannon index indicated that microbiota showed lower diversity in patients with HAM-D ≥ 8 compared to those of healthy donors and patients with HAM-D < 8. There was a significant correlation between baseline Shannon index and HAM-D score, and a correlation between Shannon index change and HAM-D improvement after FMT. Limitations: The small sample size with no control group. Conclusions: Our results suggest that depression and anxiety symptoms may be improved by FMT regardless of gastrointestinal symptom change in patients with IBS, FDr and FC, and the increase of microbiota diversity may help to improve patient's mood.

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Associations between problematic Internet use and psychiatric symptoms among university students in Japan

Kitazawa M., Yoshimura M., Murata M., Sato-Fujimoto Y., Hitokoto H., Mimura M., Tsubota K., Kishimoto T.

Psychiatry and Clinical Neurosciences （Psychiatry and Clinical Neurosciences） 72 （ 7 ） 531 - 539 2018年07月

研究論文（学術雑誌）, 査読有り, ISSN 13231316

© 2018 The Author. Psychiatry and Clinical Neurosciences © 2018 Japanese Society of Psychiatry and Neurology Aim: Research on the adverse effects of Internet use has gained importance recently. However, there is currently insufficient data on Japanese young adults’ Internet use, so we conducted a survey targeting Japanese university students to research problematic Internet use (PIU). We also investigated the relationship between PIU and multiple psychiatric symptoms. Methods: A paper-based survey was conducted at five universities in Japan. Respondents were asked to fill out self-report scales regarding their Internet dependency using the Internet Addiction Test (IAT). Sleep quality, attention-deficit hyperactivity disorder (ADHD) tendency, depression, and anxiety symptom data were also collected based on respective self-reports. Results: There were 1336 responses and 1258 were included in the analysis. The mean IAT score (± SD) was 37.87 ± 12.59; and 38.2% of participants were classified as PIU, and 61.8% as non-PIU. The trend level for young women showed that they were more likely to be classified as PIU than young men (40.6% and 35.2% respectively, P = 0.05). Compared to the non-PIU group, the PIU group used the Internet longer (P < 0.001), had significantly lower sleep quality (P < 0.001), had stronger ADHD tendencies (P < 0.001), had higher Depression scores (P < 0.001), and had higher Trait-Anxiety scores (P < 0.001). Based on multiple logistic regression analyses, the factors that contributed to an increased risk of PIU were: being female (odds ratio [OR] = 1.52), being older (OR = 1.17), having poor sleep quality (OR = 1.52), having ADHD tendencies (OR = 2.70), having depression (OR = 2.24), and having anxiety tendencies (OR = 1.43). Conclusion: We found a high PIU prevalence among Japanese young adults. The factors that predicted PIU were: female sex, older age, poor sleep quality, ADHD tendencies, depression, and anxiety.

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A practical BCG measuring system with bed sensors and algorithm for heartbeat detection

Nagura M., Mitsukura Y., Kishimoto T., Mimura M.

Proceedings - 2018 IEEE 15th International Workshop on Advanced Motion Control, AMC 2018 （Proceedings - 2018 IEEE 15th International Workshop on Advanced Motion Control, AMC 2018） 317 - 321 2018年06月

© 2018 IEEE. Ballistocardiogram (BCG) is useful and informative signal result from the cardiac activity. In this paper, we present a practical BCG measurement system with bed sensors. Moreover, the simple algorithm to detect all individual heartbeats and estimate beat-to-beat interval lengths is presented. These are effective for all night continuous monitoring of cardiovascular system and enable us to detect sleep stage. Heart beats is detected by cross-correlation method. This method has three steps, preprocessing, typical wave form creation and cross-correlation calculation. Output of this process were validated with 10 subjects. As the results, the average 71.5% of the beat-to-beat intervals were detected. Moreover this study revealed that the individual difference is significant factor to detect heart beats precisely.

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The effect of fecal microbiota transplantation on psychiatric symptoms among patients with irritable bowel syndrome, functional diarrhea and functional constipation: An open-label observational study

Kurokawa Shunya, Kishimoto Taishiro, Mizuno Shinta, Masaoka Tatsuhiro, Naganuma Makoto, Liang Kuo-ching, Kitazawa Momoko, Nakashima Moeko, Shindo Chie, Suda Wataru, Hattori Masahira, Kanai Takanori, Mimura Masaru

BIOLOGICAL PSYCHIATRY 83 （ 9 ） S268 - S268 2018年05月

ISSN 0006-3223

Electroconvulsive Therapy Induces Age-Dependent Volume Increase in the Human Dentate Gyrus

Takamiya Akihiro, Chung Jun Ku, Plitman Eric, Chakravarty Mallar, Sawada Kyosuke, Hirano Jinichi, Yamagata Bun, Graff-Guerrero Ariel, Kishimoto Taishiro, Mimura Masaru

BIOLOGICAL PSYCHIATRY 83 （ 9 ） S188 - S188 2018年05月

ISSN 0006-3223

An estimation of heart rate variability from ballistocardiogram measured with bed leg sensors

Nagura M., Mitsukura Y., Kishimoto T., Mimura M.

Proceedings of the IEEE International Conference on Industrial Technology （Proceedings of the IEEE International Conference on Industrial Technology） 2018-February 2005 - 2009 2018年04月

© 2018 IEEE. Ballistocardiogram (BCG) is the repetitive body movements related to cardiac cycle. All night continuous measuring of BCG by using bed sensors enable us to detect sleep stage. However conventional methods are seemed to have unreliability caused by position of lying down. In this paper, we propose a reliable method of all night continuous measuring of BCG. Heart rate variability (HRV) is estimated from BCG measured with new bed sensors by template-matching approach. This approach has three steps, pre-processing, template-creation and template matching. Output of this process were validated with 4 subjects. The mean beat-to-beat interval error was 9.8[ms] and on an average 87.1% of the beat-to-beat intervals were detected.

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BREAKTHROUGH ON ANTIPSYCHOTIC MAINTENANCE MEDICATION: A STUDY-LEVEL META-ANALYSIS AND META-REGRESSION ANALYSI

Rubio J, Ahmed K, Correll C, Hagi K, Kishimoto T, Kane J.

Schizophrenia bulletin 44 （ suppl_1 ） S207 - S208 2018年04月

研究論文（国際会議プロシーディングス）, 共著

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Effect of electroconvulsive therapy on hippocampal and amygdala volumes: Systematic review and meta-analysis

Takamiya A., Chung J., Liang K., Graff-Guerrero A., Mimura M., Kishimoto T.

British Journal of Psychiatry （British Journal of Psychiatry） 212 （ 1 ） 19 - 26 2018年01月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 00071250

© 2018 The Royal College of Psychiatrists. Background Electroconvulsive therapy (ECT) is one of the most effective treatments for depression, although the underlying mechanisms remain unclear. Animal studies have shown that electroconvulsive shock induced neuroplastic changes in the hippocampus. Aims To summarise volumetric magnetic resonance imaging studies investigating the effects of ECT on limbic brain structures. Method A systematic review and meta-analysis was conducted to assess volumetric changes of each side of the hippocampus and amygdala before and after ECT. Standardised mean difference (SMD) was calculated. Results A total of 8 studies (n = 193) were selected for our analyses. Both right and left hippocampal and amygdala volumes increased after ECT. Meta-regression analyses revealed that age, percentage of those responding and percentage of those in remission were negatively associated with volume increases in the left hippocampus. Conclusions ECT increased brain volume in the limbic structures. The clinical relevance of volume increase needs further investigation.

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音声データを用いたうつ病重症度の深層学習解析

四井美月, Liang Kuo-ching, 廣原茉耶, 北沢桃子, 吉村道孝, 江口洋子, 藤田卓仙, 岸本泰士郎, 榊原康文

人工知能学会全国大会論文集（一般社団法人人工知能学会） 2018 （ 0 ） 4C2OS27b02 - 4C2OS27b02 2018年

精神疾患の診断は現在，問診に基づく医師の主観的判断によって行われている．このような現在の診断方法は医師の経験に強く依存するため，正確な診断を行うための客観的な診断方法を開発する必要があると言われている．したがって我々の目標は，デバイスによって記録されたデータからうつ病患者の重症度を客観的に計算する深層学習手法を構築することである．本研究では，うつ病患者と健常者を音声データで分類する深層学習プログラムを開発する．

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不安障害における時間概念と感情価の連合:潜在連合テストによる検討

伊藤友一, 百田友紀, 岸本泰士郎, 三村將, 梅田聡

日本認知心理学会発表論文集（日本認知心理学会） 2018 （ 0 ） 2018年

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不安障害における時間概念と感情価の連合:潜在連合テストによる検討

伊藤友一, 百田友紀, 岸本泰士郎, 三村將, 梅田聡

日本認知心理学会発表論文集（日本認知心理学会） 2018 （ 0 ） 2018年

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Effectiveness of Long-Acting Injectable vs Oral Antipsychotics in Patients With Schizophrenia: A Meta-analysis of Prospective and Retrospective Cohort Studies

Kishimoto T., Hagi K., Nitta M., Leucht S., Olfson M., Kane J., Correll C.

Schizophrenia Bulletin （Schizophrenia Bulletin） 44 （ 3 ） 603 - 619 2017年07月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 05867614

© The Author(s) 2017. Compared with oral antipsychotics (OAPs), long-acting injectable antipsychotics (LAIs) should improve medication adherence and reduce relapses in schizophrenia. However, meta-analyses of randomized trials and mirror-image studies yielded inconsistent results. Nonrandomized cohort studies with parallel comparisons of LAIs and OAPs offer a third design to examine this issue. We meta-analyzed cohort studies with ≥24 weeks duration and hospitalization data. Primary outcome was hospitalization rate, ie, number of hospitalizations per person-year. Secondary outcomes included hospitalization risk, ie, proportion of patients experiencing ≥1 hospitalizations, all-cause discontinuation, and total hospitalization days. Patient severity and/or chronicity at baseline was also meta-analyzed and explored as a potential effect size moderator. Altogether, 42 studies (n = 101 624; follow-up = 18.6 ± 10.0 mo) were meta-analyzed. LAIs were superior to OAPs regarding hospitalization rate (studies = 15, person-years = 68 009, rate ratio = 0.85, 95% CI = 0.78-0.93, P < .001) and all-cause discontinuations (studies = 10, n = 37 293, risk ratio = 0.78, 95% CI = 0.67-0.91, P = .001), but not regarding hospitalization risk (studies = 33, n = 51 733, risk ratio = 0.92, 95% CI = 0.84-1.00, P = .06), and hospitalization days (studies = 11, n = 21 328, Hedges' g = -0.05, 95% CI = -0.16 to 0.06, P = .39). Illness severity/chronicity was significantly greater in patients prescribed LAIs vs OAPs when all available information was pooled together (studies = 23, n = 61 806, Hedges' g = 0.15, 95% CI = 0.03-0.26, P = .01), but not when examined separately. In summary, this metaanalysis of cohort studies, which included patients that are broadly representative of clinical practice, indicates that LAIs are superior to OAPs. The lack of significant superiority of LAIs for hospitalization risk and hospital days needs to be interpreted in the context of naturalistic treatment selection with subsequently greater illness severity/chronicity in LAI-treated patients.

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Bifidobacterium-Rich Fecal Donor May Be a Positive Predictor for Successful Fecal Microbiota Transplantation in Patients with Irritable Bowel Syndrome.

Mizuno S, Masaoka T, Naganuma M, Kishimoto T, Kitazawa M, Kurokawa S, Nakashima M, Takeshita K, Suda W, Mimura M, Hattori M, Kanai T.

Digestion 96 （ (1) ） 29 - 38 2017年06月

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テレビ会議システムを用いた時計描画検査の信頼性, 高次脳機能研究

飯干紀代子, 岸本泰士郎, 江口洋子, 加藤佑佳, 松岡照之, 成本迅, 三村將.

高次脳機能研究（株式会社新興医学出版社） 37 （ (2) ） 220 - 227 2017年06月

査読有り, ISSN 1348-4818

Indications for and use of long-acting injectable antipsychotics: consideration from an inpatient setting

Kishimoto T, Sanghani S, Russ MJ, Marsh AN, Morris J, Basu S, Kane JM.

International Clinical Psychopharmacolo 32 （ (3) ） 161 - 168 2017年05月

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Smartphone Viewing Distance and Sleep: An Experimental Study Utilizing Motion Capture Technology

Yoshimura M, Kitazawa M, Maeda Y, Mimura M, Tsubota K, Kishimoto T

Nature and Science of Sleep 9 59 - 65 2017年03月

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Comparison of treatment patterns in schizophrenia between China and Japan (2001-2009)

Xiang YT, Kato TA, Kishimoto T, Ungvari GS, Chiu HF, Si TM, Yang SY, Fujii S, Ng CH, Shinfuku N.

Asia-Pacific Psychiatry 2017年02月

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Predictors of readmission after successful electroconvulsive therapy for depression: a chart review study.

''Uchida T, Kishimoto T, Koreki A, Nakao S, Owada A, Koizumi T, Saito A, Sato M,Sawada S, Matsuzaki R, Petrides G, Mimura M

Int J Psychiatry Clin Pract 20 （ (4) ） 260 - 264 2016年11月

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Attenuated psychotic and basic symptom characteristics in adolescents with ultra-high risk criteria for psychosis, other non-psychotic psychiatric disorders and early-onset psychosis.

Lo Cascio N, Saba R, Hauser M, Vernal DL, Al-Jadiri A, Borenstein Y, Sheridan EM, Kishimoto T, Armando M, Vicari S, Fiori Nastro P, Girardi P, Gebhardt E, Kane JM, Auther A, Carrión RE, Cornblatt BA, Schimmelmann BG, Schultze-Lutter F, Correll CU

Eur Child Adolesc Psychiatry 25 （ (10) ） 1091 - 1102 2016年10月

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Safety and tolerability of long-acting injectable versus oral antipsychotics: a meta-analysis of randomized controlled studies comparing the same antipsychotics.

''Misawa F, Hagi K, Kishimoto T, Kane JM, Correll CU

Schizophrenia Research 176 （ (2-3) ） 220 - 230 2016年10月

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Sleep and mood disorders in women with dry eye disease.

Ayaki M, Kawashima M, Negishi K, Kishimoto T, Mimura M, Tsubota K

Scientific Reports 2016年10月

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Sleep and mood disorders in dry eye disease and allied irritating ocular diseases.

Ayaki M, Kawashima M, Negishi K, Kishimoto T, Mimura M, Tsubota K

Sci Rep 6 2016年03月

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Factors associated with discontinuation of aripiprazole treatment after switching from other antipsychotics in patients with chronic schizophrenia: A prospective observational study

''Takaesu Y, Kishimoto T, Murakoshi A, Takahashi N, Inoue Y

Psychiatry Res 236 71 - 74 2016年02月

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Attenuated psychotic and basic symptom characteristics in adolescents with ultra-high risk criteria for psychosis, other non-psychotic psychiatric disorders and early-onset psychosis

Eur Child Adolesc Psychiatry 25 （ (10) ） 1091 - 1102 2016年02月

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Single-dose infusion ketamine and non-ketamine N-methyl-d-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories.

Kishimoto T, Chawla JM, Hagi K, Zarate CA, Kane JM, Bauer M, Correll CU.

Psychol Med 46 （ (7) ） 1459 - 1472 2016年02月

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Worldwide differences in regulations of clozapine use.

Nielsen J, Young C, Ifteni P, Kishimoto T, Xian YT, Schukte PF, Correll CU, Taylor D

CNS Drugs 30 （ (2) ） 149 - 161 2016年02月

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高齢者に対するビデオ会議システムを用いた改訂長谷川式簡易知能評価スケールの信頼性試験

岸本泰士郎, 江口洋子, 飯干紀代子, 北沢桃子, 梁國經, 船木桂, 成本迅, 三村將

日本遠隔医療学会雑誌 12 （ 2 ） 145 - 148 2016年

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A Survey of Japanese young adult’s postures when using smartphones before sleeping.

Yoshimura M, Kitazawa M, Kishimoto T, Mimura M, Tsubota K

Journal of Mobile Technology in Medicine 5 （ 2 ） 51 - 53 2016年

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統合失調症患者における死亡率と突然死についての検討

五十嵐桂, 藤井康男, 三澤史斉, 岸本泰士郎

臨床精神薬理 19 （ (7) ） 1003 - 1014 2016年

研究論文（学術雑誌）, 共著, 査読有り

臨床研究デザインの限界に注目しながら持効性注射剤（LAI）の効果について検証する―LAI賛成の立場から―

岸本泰士郎

精神神経学雑誌 118 （ (8) ） 607 - 614 2016年

研究論文（学術雑誌）, 単著, 査読有り

遠隔で行った強迫症に対する曝露反応妨害法：3症例のケースシリーズ

岸本泰士郎, 垂水沙梨, 中前貴, 三村將

臨床精神医学 45 （ (12) ） 1603 - 1609 2016年

査読有り

Frequency and correlates of DSM-5 attenuated psychosis syndrome in a sample of adolescent inpatients with nonpsychotic psychiatric disorders.

Gerstenberg M, Hauser M, Al-Jadiri A, Sheridan EM, Kishimoto T, Borenstein Y, Vernal DL, David L, Saito E, Landers SE, Carella M, Singh S, Carbon M, Jiménez-Fernández S, Birnbaum ML, Auther A, Carrión RE, Cornblatt BA, Kane JM, Walitza S, Correll CU

J Clin Psychiatry 76 （ (11) ） 1449 - 1458 2015年11月

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Transcranial Magnetic Stimulation for Bipolar Disorder with Catatonic Stupor: A Case Report.

''Takamiya A, Kishimoto T, Watanabe K, Mimura M, Kito S

Brain Stimul 8 （ (6) ） 1236 - 1237 2015年11月

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Do Long-Acting Injectable Antipsychotics Improve Adherence and Related Outcomes?

Christoph U. Correll, MD; Kishimoto T, MD; John M. Kane, MD

2015年09月

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Ambiguous findings concerning potential advantages of depot antipsychotics: in search of clinical relevance

''Haddad PM, Kishimoto T, Correll CU, Kane JM

Curr Opin Psychiatry 28 （ (3) ） 216 - 221 2015年05月

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Capacity test in financial activities of elderly: Preliminary study

Iiboshi K, Kohriyama K, Kato Y, Matsuoka T, Narumoto J, Eguchi Y, Kishimoto T, Mimura M, Awazu K, Iwamaru H.

INTERNATIONAL PSYCHOGERIATRICS 27 S141 - S142 2015年

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The Bipolar Prodrome Symptom Interview and Scale-Prospective (BPSS-P): description and validation in a psychiatric sample and healthy controls

Correll CU, Olvet DM, Auther AM, Hauser M, Kishimoto T, Carrión RE, Snyder S, Cornblatt BA

Bipolar Disord. 16 （ (5) ） 505 - 522 2014年08月

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Long-acting injectable vs oral antipsychotics for relapse prevention in schizophrenia: a meta-analysis of randomized trials.

Kishimoto T, Robenzadeh A, Leucht C, Leucht S, Watanabe K, Mimura M, Borenstein M, Kane JM, Correll CU

Schizophr Bull 40 （ (1) ） 192 - 213 2014年01月

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New developments in the early recognition of individuals at risk for or with emerging schizophrenia and bipolar spectrum disorders.

Correll C, Kishimoto T, Loewy R, Kane JM

（Early Intervention in Psychiatry） 8 （ 29 ） 29 2014年

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Early nonresponse determined by the clinical global impressions scale predicts poorer outcomes in youth with schizophrenia spectrum disorders naturalistically treated with second-generation antipsychotics.

Stentebjerg-Olesen M, Jeppesen P, Pagsberg AK, Fink-Jensen A, Kapoor S, Chekuri R, Carbon M, Al-Jadiri A, Kishimoto T, Kane JM, Correll CU

J Child Adolesc Psychopharmacol. 23 （ (10) ） 665 - 675 2013年12月

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Adjunctive use of nonsteroidal anti-inflammatory drugs for schizophrenia: a meta-analytic investigation of randomized controlled trials

Nitta M, Kishimoto T, Müller N, Weiser M, Davidson M, Kane JM, Correll CU

Schizophr Bull 39 （ (6) ） 1230 - 1241 2013年11月

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An open-label study of algorithm-based treatment versus treatment-as-usual for patients with schizophrenia

Hirano J, Watanabe K, Suzuki T, Uchida H, Den R, Kishimoto T, Nagasawa T, Tomita Y, Hara K, Ochi H, Kobayashi Y, Ishii M, Fujita A, Kanai Y, Goto M, Hayashi H, Inamura K, Ooshima F, Sumida M, Ozawa T, Sekigawa K, Nagaoka M, Yoshimura K, Konishi M, Inagaki A, Saito T, Motohashi N, Mimura M, Okubo Y, Kato M

Neuropsychiatr Dis Treat 9 1553 - 1564 2013年10月

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Long Acting Injectable vs. Oral Antipsychotics in Schizophrenia: A Systematic Review and Meta-Analysis of Mirror-Image Studies

Kishimoto T, Nitta M, Borenstein M, Kane JM, Correll CU

J Clin Psychiatry 74 （ (10) ） 957 - 965 2013年10月

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Antipsychotic polypharmacy: a Japanese survey of prescribers' attitudes and rationales

Kishimoto T, Watanabe K, Uchida H, Mimura M, Kane JM, Correll CU.

Psychiatry Res 209 （ (3) ） 406 - 411 2013年10月

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Non-adherence to medication in patients with psychotic disorders: epidemiology, contributing factors and management strategies

Kane JM, Kishimoto T, Correll CU

World Psychiatry 12 （ (3) ） 216 - 226 2013年10月

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Assessing the comparative effectiveness of long-acting injectable vs. oral antipsychotic medications in the prevention of relapse provides a case study in comparative effectiveness research in psychiatry

Kane JM, Kishimoto T, Correll CU

J Clin Epidemiol 66 （ (8 Suppl) ） S37 - S41 2013年08月

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The impact of prolactin-raising antipsychotics on bone mineral density in patients with schizophrenia: findings from a longitudinal observational cohort

Takahashi T, Uchida H, John M, Hirano J, Watanabe K, Mimura M, Correll CU, Kishimoto T

Schizophr Res 147 （ (2-3) ） 383 - 386 2013年07月

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Relapse prevention in schizophrenia: a systematic review and meta-analysis of second-generation antipsychotics versus first-generation antipsychotics

Kishimoto T, Agarwal V, Broday A, Kishi T, Geiman G, Kane JM, Correll C.

Mol Psychiatry 18 （ (1) ） 53 - 66 2013年01月

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The 3rd Schizophrenia International Research Society Conference, 14-18 April 2012, Florence, Italy: summaries of oral sessions.

Abbs B, Achalia RM, Adelufosi AO, Aktener AY, Beveridge NJ, Bhakta SG, Blackman RK, Bora E, Byun MS, Cabanis M, Carrion R, Castellani CA, Chow TJ, Dmitrzak-Weglarz M, Gayer-Anderson C, Gomes FV, Haut K, Hori H, Kantrowitz JT, Kishimoto T, Lee FH, Lin A, Palaniyappan L, Quan M, Rubio MD, Ruiz de Azúa S, Sahoo S, Strauss GP, Szczepankiewicz A, Thompson AD, Trotta A, Tully LM, Uchida H, Velthorst E, Young JW, O'Shea A, Delisi LE

Schizophr Res 141 （ (1) ） e1 - e24 2012年10月

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Osteoporosis and fracture risk in people with schizophrenia.

Kishimoto T, De Hert M, Carlson HE, Manu P, Correll CU.

Curr Opin Psychiatry 25 （ (5) ） 415 - 429 2012年09月

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Antipsychotic polypharmacy: A survey study of prescriber attitudes, knowledge and behavior.

Correll CU, Shaikh L, Gallego JA, Nachbar J, Olshanskiy V, Kishimoto T, Kane JM

Schizophr Res 131 （ (1-3) ） 58 - 62 2011年05月

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Quantifying clinical relevance in the treatment of schizophrenia

Correll CU, Kishimoto T, Nielson J, Kane JM

Clinical therapeutics 33 （ (12) ） B16 - B39 2011年

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Randomized controlled trials in schizophrenia: opportunities, limitations, and trial design alternatives.

Correll CU, Kishimoto T, Kane JM

Dialogues Clin Neurosci. 13 （ (2) ） 155 - 172 2011年

研究論文（学術雑誌）, 共著, 査読有り

Review: most antipsychotic drugs more than double the prolactin levels in children and adolescents.

''Correll C, Kishimoto T, Carlson H.

Evid Based Ment Health. 13 （ (2) ） 54 2010年05月

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Antipsychotic-induced hyperprolactinemia inhibits the hypothalamo-pituitary-gonadal axis and reduces bone mineral density in male patients with schizophrenia

Kishimoto T, Watanabe K, Shimada N, Makita K, Yagi G, Kashima H

J Clin Psychiatry 69 （ (3) ） 385 - 391 2008年03月

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Bone mineral density measurement in female inpatients with schizophrenia.

Kishimoto T, Watanabe K, Takeuchi H, Kikuchi T, Nakajima S, Shimada N, Yagi G, Kashima H

Schizophr Res 77 （ 1 ） 113 - 115 2005年09月

研究論文（学術雑誌）, 査読有り

PCCX1, a novel　DNA-binding protein with PHD finger and CXXC domain, is regulated by proteolysis.

Fujino T, Hasegawa M, Shibata S, Kishimoto T, Imai S, Takano T

Biochem Biophys Res Commun 271 （ (2) ） 305 - 310 2000年05月

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