研究者詳細 - 三村　将

論文 - 三村　将

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Reproductive history and risk of cognitive impairment in Japanese women

Shimizu Y., Sawada N., Iwasaki M., Shikimoto R., Nozaki S., Mimura M., Tsugane S.

Maturitas （Maturitas） 128 22 - 28 2019年10月

ISSN 03785122

© 2019 Objective: While exposure to endogenous estrogen may be associated with better cognitive performance, it is still unclear whether it has an association with mild cognitive impairment (MCI) or dementia. The aim of this study was to clarify the effects of reproductive history, as a surrogate marker of exposure to endogenous estrogen, on the risk of cognitive impairment (MCI or dementia) in women. Study design: A total of 747 women aged 40–59 years in the Saku area (Nagano Prefecture) were followed as part of the Japan Public Health Center-based Prospective (JPHC) Study, which started in 1990. Participants had undergone a mental health examination in 2014–2015. Main outcome measures: We used multiple logistic regression to analyze the association between reproductive history, obtained at baseline and 10-year follow-up, with current cognitive impairment diagnosed by a trained psychiatrist, adjusting for various lifestyle factors. Results: Among 670 eligible women, current cognitive impairment was diagnosed in 227, 196 of whom had MCI and 31 dementia. A longer reproductive period had a significantly inverse association with cognitive impairment (P-trend = 0.032). In particular, women with a reproductive period ≥38 years compared with ≤33 years had a significantly lower risk of cognitive impairment (multivariable adjusted odds ratio=0.62, 95% confidence interval=0.40–0.96). Conclusions: A longer reproductive period was associated with a lower risk of cognitive impairment, which suggests that a longer exposure to endogenous estrogen may have a protective effect against cognitive impairment.

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

Takamiya A., Kishimoto T., Liang K.c., 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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Acute and long-term effects of electroconvulsive therapy on human dentate gyrus

Takamiya A., Plitman E., Chung J.K., Chakravarty M., Graff-Guerrero A., Mimura M., Kishimoto T.

Neuropsychopharmacology （Neuropsychopharmacology） 44 （ 10 ） 1805 - 1811 2019年09月

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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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

ISSN 02681315

© 2019 Wolters Kluwer Health, Inc. 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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Attitudes Toward Electroconvulsive Therapy among Involuntary and Voluntary Patients

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

Journal of ECT （Journal of ECT） 35 （ 3 ） 165 - 169 2019年09月

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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Alteration in AMPA receptor subunit expression and receptor binding among patients with addictive disorders: A systematic review of human postmortem studies

Ueno F., Suzuki T., Nakajima S., Matsushita S., Mimura M., Miyazaki T., Takahashi T., Uchida H.

Neuropsychopharmacology Reports （Neuropsychopharmacology Reports） 39 （ 3 ） 148 - 155 2019年09月

© 2019 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd. Background and Objectives: Altered trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors has been reported in postmortem studies and suggested the involvement of AMPA receptors in the pathophysiology underpinning addictive disorders. However, these findings seemed mixed. Methods: A systematic literature search was conducted, using PubMed and Embase (last search, August 2018), to identify human postmortem studies that examined the expression of proteins and mRNA of AMPA receptor subunits in patients with addictive disorders in comparison with healthy controls. Results: Twelve (18 studies) out of 954 articles were identified to be relevant. Eight studies included alcohol use disorders, and four studies included heroin/cocaine abusers. The most frequently investigated regions were the hippocampus (three studies), amygdala (three studies), and putamen (three studies). In summary, two out of the three studies showed an increase in the expression of AMPA receptors in the hippocampus, while the other study found no change. Two studies to examine the amygdala demonstrated either a decreased or no change in receptor expression or binding. Concerning putamen, two studies showed no significant change whereas an overexpression of receptors was observed in the other. Conclusions and Scientific Significance: The hippocampus and amygdala may be pertinent to addictive disorders through their functions on learning and memory, whereas findings in other regions were inconsistent across the studies. Human postmortem studies are prone to degenerative changes after death. Moreover, only qualitative assessment was conducted because of the limited, heterogenous data. These limitations emphasize the need to investigate AMPA receptors in the living human brains.

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Impairment in judgement of the moral emotion guilt following orbitofrontal cortex damage

Funayama M., Koreki A., Muramatsu T., Mimura M., Kato M., Abe T.

Journal of Neuropsychology （Journal of Neuropsychology） 13 （ 3 ） 550 - 563 2019年09月

ISSN 17486645

© 2018 The British Psychological Society Although neuroimaging studies have provided evidence for an association between moral emotions and the orbitofrontal cortex, studies on patients with focal lesions using experimental probes of moral emotions are scarce. Here, we addressed this topic by presenting a moral emotion judgement task to patients with focal brain damage. Four judgement tasks in a simple pairwise choice paradigm were given to 72 patients with cerebrovascular disease. These tasks consisted of a perceptual line judgement task as a control task; the objects’ preference task as a basic preference judgement task; and two types of moral emotion judgement task, an anger task and a guilt task. A multiple linear regression analysis was performed on each set of task performance scores to take into account potential confounders. Performance on the guilt emotion judgement task negatively correlated with the orbitofrontal cortex damage, but not with the other variables. Results for the other judgement tasks did not reach statistical significance. The close association between orbitofrontal cortex damage and a decrease in guilt emotion judgement consistency might suggest that the orbitofrontal cortex plays a key role in the sense of guilt, a hallmark of morality.

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The P300 event-related potential in bipolar disorder: A systematic review and meta-analysis

Wada M., Kurose S., Miyazaki T., Nakajima S., Masuda F., Mimura Y., Nishida H., Ogyu K., Tsugawa S., Mashima Y., Plitman E., Chakravarty M.M., Mimura M., Noda Y.

Journal of Affective Disorders （Journal of Affective Disorders） 256 234 - 249 2019年09月

ISSN 01650327

© 2019 Background: Neurophysiology including P300, that is a typical index of event-related potential, may be potential biomarkers for bipolar disorder (BD) and it can be useful towards elucidating the pathophysiology of BD. However, previous findings from P300 studies were inconsistent due to the heterogeneity of research methods, which make it difficult to understand the neurobiological significance of them. The aim of this study is to conduct a meta-analysis on P300 in patients with BD. Method: A literature search was conducted using PubMed to identify studies that compared P300 event-related potential between patients with BD and healthy controls (HCs). We analyzed P300 indices such as amplitude and latency of P3a and P3b in auditory or visual paradigms. Further, moderator analyses were conducted to investigate the influence of patient characteristics (i.e. history of psychosis, diagnostic subcategories [BD-I/BD-II], and phase of illness [euthymic, manic, or depressive]) on P300 indices. Result: Out of 124 initial records, we included 30 articles (BD: N = 1331; HCs: N = 1818). Patients with BD showed reduced P3a and P3b amplitude in both paradigms and delayed P3b latency in auditory paradigms compared to HCs. There was no influence on the history of psychosis, diagnostic subcategories, or phase of illness on P300 indices. Limitation: The difference in medication use was difficult to control and it may affect the results. Conclusion: This meta-analysis provides evidence for P300 abnormalities in patients with BD compared to HCs. Our results suggest that P300 may be trait markers rather than state markers in this illness.

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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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Brief Report: Olfactory Adaptation in Children with Autism Spectrum Disorders

Kumazaki H., Muramatsu T., Miyao M., Okada K.i., Mimura M., Kikuchi M.

Journal of Autism and Developmental Disorders （Journal of Autism and Developmental Disorders） 49 （ 8 ） 3462 - 3469 2019年08月

ISSN 01623257

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. Olfactory adaptation is an important process that allows the individual to adjust to changes in the environment. This process has been proposed to be aberrant in individuals with autism spectrum disorders (ASD). However, few studies have examined olfactory adaptation in children with ASD. We examined olfactory adaptation in children with ASD and typically developing (TD) children using a pulse ejection system, which resolved problems associated with previous laboratory-based olfactory psychophysical studies. Nine children with ASD and nine TD children participated in this study and all participants completed the entire experiment. Using this system, we found that the TD group showed greater adaptation than the ASD group. Our results provide a better understanding of olfactory adaptation in children with ASD.

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Job interview training targeting nonverbal communication using an android robot for individuals with autism spectrum disorder

Kumazaki H., Muramatsu T., Yoshikawa Y., Corbett B.A., Matsumoto Y., Higashida H., Yuhi T., Ishiguro H., Mimura M., Kikuchi M.

Autism （Autism） 23 （ 6 ） 1586 - 1595 2019年08月

ISSN 13623613

© The Author(s) 2019. Job interviews are significant barriers for individuals with autism spectrum disorder because these individuals lack good nonverbal communication skills. We developed a job interview training program using an android robot. The job interview training program using an android robot consists the following three stages: (1) tele-operating an android robot and conversing with others through the android robot, (2) a face-to-face mock job interview with the android robot, and (3) feedback based on the mock job interview and nonverbal communication exercises using the android robot. The participants were randomly assigned to the following two groups: one group received a combined intervention with “interview guidance by teachers and job interview training program using an android robot” (n = 13), and the other group received an intervention with interview guidance by teachers alone (n = 16). Before and after the intervention, the participants in both groups underwent a mock job interview with a human interviewer, who provided outcome measurements of nonverbal communication, self-confidence, and salivary cortisol. After the training sessions, the participants who received the combined interview guidance by teachers and the job interview training program using an android robot intervention displayed improved nonverbal communication skills and self-confidence and had significantly lower levels of salivary cortisol than the participants who only received interview guidance by teachers. The job interview training program using an android robot improved various measures of job interview skills in individuals with autism spectrum disorder.

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Prediction of deficiency-excess pattern in Japanese Kampo medicine: Multi-centre data collection

Maeda-Minami A., Yoshino T., Katayama K., Horiba Y., Hikiami H., Shimada Y., Namiki T., Tahara E., Minamizawa K., Muramatsu S., Yamaguchi R., Imoto S., Miyano S., Mima H., Mimura M., Nakamura T., Watanabe K.

Complementary Therapies in Medicine （Complementary Therapies in Medicine） 45 228 - 233 2019年08月

ISSN 09652299

© 2019 Elsevier Ltd Objective: The purpose of the present study was to compare important patient questionnaire items by creating a random forest model for predicting deficiency-excess pattern diagnosis in six Kampo specialty clinics. Design: A multi-centre prospective observational study. Setting: Participants who visited six Kampo specialty clinics in Japan from 2012 to 2015. Main outcome measure: Deficiency-excess pattern diagnosis made by board-certified Kampo experts. Methods: To predict the deficiency-excess pattern diagnosis by Kampo experts, we used 153 items as independent variables, namely, age, sex, body mass index, systolic and diastolic blood pressures, and 148 subjective symptoms recorded through a questionnaire. We extracted the 30 most important items in each clinic's random forest model and selected items that were common among the clinics. We integrated participating clinics’ data to construct a prediction model in the same manner. We calculated the discriminant ratio using this prediction model for the total six clinics’ data and each clinic's independent data. Results: Fifteen items were commonly listed in top 30 items in each random forest model. The discriminant ratio of the total six clinics’ data was 82.3%; moreover, with the exception of one clinic, the independent discriminant ratio of each clinic was approximately 80% each. Conclusions: We identified common important items in diagnosing a deficiency-excess pattern among six Japanese Kampo clinics. We constructed the integrated prediction model of deficiency-excess pattern.

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Resting-state hyperperfusion in the whole brain: A case of malignant catatonia that improved with electric convulsion therapy

Kurose S., Koreki A., Funayama M., Takahashi E., Kaji M., Ogyu K., Takasu S., Koizumi T., Suzuki H., Onaya M., Mimura M.

Schizophrenia Research （Schizophrenia Research） 210 287 - 288 2019年08月

ISSN 09209964

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

Moriguchi S., Takamiya A., Noda Y., Horita N., Wada M., Tsugawa S., Plitman E., Sano Y., Tarumi R., ElSalhy M., Katayama N., Ogyu K., Miyazaki T., Kishimoto T., Graff-Guerrero A., Meyer J.H., Blumberger D.M., Daskalakis Z.J., Mimura M., Nakajima S.

Molecular Psychiatry （Molecular Psychiatry） 24 （ 7 ） 952 - 964 2019年07月

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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Model-guided antipsychotic dose reduction in schizophrenia: A pilot, single-blind randomized controlled trial

Ozawa C., Bies R.R., Pillai N., Suzuki T., Mimura M., Uchida H.

Journal of Clinical Psychopharmacology （Journal of Clinical Psychopharmacology） 39 （ 4 ） 329 - 335 2019年07月

ISSN 02710749

© 2019 Wolters Kluwer Health, Inc. All rights reserved. Purpose/Background Patients with schizophrenia as well as their psychiatrists are hesitant to reduce the antipsychotic dose in fear of relapse. To overcome such dilemmas, we developed models to individually calculate an oral dose that corresponds to a given target dopamine D2 receptor occupancy. Methods/Procedures In this pilot, 52-week single-blind randomized controlled trial, 35 clinically stable patients with schizophrenia receiving either risperidone or olanzapine monotherapy were randomly assigned to dose reduction (n = 17) or dose maintenance group (n = 18). In the former group, baseline doses were reduced to the doses corresponding to 65% D2 occupancy (the lower end of therapeutic window) at trough that were calculated from randomly collected plasma concentrations using our models. Findings/Results In the dose reduction group, doses of risperidone and olanzapine were decreased from 4.2 ± 1.9 to 1.4 ± 0.4 and 12.8 ± 3.9 to 6.7 ± 1.8 mg/d, whereas the doses in the dose maintenance group were 4.3 ± 1.9 and 15.8 ± 4.6 mg/d, respectively. Twelve subjects (70.5%) and 13 subjects (72.2%) in the dose reduction and dose maintenance groups completed the study (P = 0.604), whereas 3 subjects (18.8%) and none dropped out because of clinical worsening in the dose reduction and dose maintenance groups, respectively. There were not significant differences in score changes in Positive and Negative Syndrome Scale between the 2 groups but in Positive subscale scores in the Clinical Global Impression-Schizophrenia (0.4 ± 0.7 in the dose reduction group vs -0.1 ± 0.7 in the dose maintenance group, P = 0.029). Implications/Conclusions Although our model-guided dose reduction strategy was found to be comparable with no-dose change in terms of dropout rates, safety issues have to be further examined.

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Can we predict amyloid deposition by objective cognition and regional cerebral blood flow in patients with subjective cognitive decline?

Funaki K., Nakajima S., Noda Y., Wake T., Ito D., Yamagata B., Yoshizaki T., Kameyama M., Nakahara T., Murakami K., Jinzaki M., Mimura M., Tabuchi H.

Psychogeriatrics （Psychogeriatrics） 19 （ 4 ） 325 - 332 2019年07月

ISSN 13463500

© 2019 Japanese Psychogeriatric Society Background: Subjective cognitive decline (SCD) may herald the first symptoms of Alzheimer's disease (AD) whereas individuals with beta-amyloid (Aβ) deposition are regarded as a high-risk group for AD. Recently, amyloid positron emission tomography (PET) studies have demonstrated clinical and cognitive feature differences between Aβ-positive and negative SCD, but details of their differences remain unclear. We aimed to investigate the relationships among Aβ deposition, clinical, and cognitive features in patients with SCD. Methods: Forty-two patients with SCD (22 women, 74.5 ± 4.7 years) were examined using fluorine-18 florbetaben PET and were divided into Aβ-positive (n = 10) and negative (n = 32) groups. We compared cognitive and psychological outcomes, and single photon emission computed tomography (SPECT) imaging data between the two groups. In addition, a linear regression analysis was performed to assess relationships between the severity of SCD and neuropsychological tests, affective scores, and demographic factors. Results: The rate of score changes from the immediate recall to delayed recall in the logical memory subtest of the Wechsler's Memory Scale Revised were different between the groups (P = 0.04). However, the binary logistic regression analysis showed no significant differences between the two. In addition, the severity of SCD was significantly strong in women (P = 0.002). Furthermore, within the Aβ-negative group, subjective memory loss correlated with word fluency category score (P = 0.023) and apathy scale (P = 0.037). Conclusions: No significant differences were observed between Aβ-positive and -negative SCD on any of the neuropsychological measures, clinical measures, or SPECT imaging. Further, the severity of SCD was not predicted by the symptoms of anxiety, depression, or neuropsychological examination.

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Does the rapid response of an antidepressant contribute to better cost-effectiveness? Comparison between mirtazapine and SSRIs for first-line treatment of depression in Japan

Sado M., Wada M., Ninomiya A., Nohara H., Kosugi T., Arai M., Endo R., Mimura M.

Psychiatry and Clinical Neurosciences （Psychiatry and Clinical Neurosciences） 73 （ 7 ） 400 - 408 2019年07月

ISSN 13231316

© 2019 The Authors. Psychiatry and Clinical Neurosciences © 2019 Japanese Society of Psychiatry and Neurology Aim: Previous studies indicate that mirtazapine is unique in its quick responsiveness compared to other antidepressants. Although some other studies have evaluated its cost-effectiveness, they have not considered its early stage remission rate. The aim of this study was to address this research gap by using precise clinical data to evaluate the cost-effectiveness of mirtazapine in Japan. Methods: We developed a Markov model to reflect the week-by-week transition probabilities. The Markov cycle was set as 1 week. While our clinical parameters were obtained largely from existing meta-analyses, cost data were derived from government reports. Cost-effectiveness was evaluated by incremental cost-effectiveness ratios (ICERs) per quality-adjusted life year estimated based on the probability sensitivity analyses. The ICERs were estimated at 2, 8, 26, and 52 weeks. Results: In severe depression, the ICERs ranged between JPY 872 153 and 1 772 723. The probability of mirtazapine being cost-effective ranged from 0.75 to 0.99 when the ICER threshold was JPY 5 000 000. In moderate depression, the ICERs ranged between JPY 2 356 499 and 4 770 145. The probability of mirtazapine being cost-effective ranged from 0.55 to 0.83 when the ICER threshold was JPY 5 000 000. Conclusion: When considering the early stage efficacy of mirtazapine, it appeared to be cost-effective compared to selective serotonin reuptake inhibitors, especially for severe depression and in the early stage treatment in the Japanese setting. However, our study has some limitations. First, mirtazapine is compared with batched selective serotonin reuptake inhibitors rather than individual ones. Second, we did not consider antidepressant combination therapy as treatment options.

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Cortical surface architecture endophenotype and correlates of clinical diagnosis of autism spectrum disorder

Yamagata B., Itahashi T., Fujino J., Ohta H., Takashio O., Nakamura M., Kato N., Mimura M., Hashimoto R.i., Aoki Y.Y.

Psychiatry and Clinical Neurosciences （Psychiatry and Clinical Neurosciences） 73 （ 7 ） 409 - 415 2019年07月

ISSN 13231316

© 2019 The Authors. Psychiatry and Clinical Neurosciences © 2019 Japanese Society of Psychiatry and Neurology Aim: Prior structural magnetic resonance imaging studies demonstrated atypical gray matter characteristics in siblings of individuals with autism spectrum disorder (ASD). However, they did not clarify which aspect of gray matter is related to the endophenotype (i.e., genetic vulnerability) of ASD. Further, because they did not enroll siblings of typically developing (TD) people, they may have underestimated the difference between individuals with ASD and their unaffected siblings. The current study aimed to address these gaps. Methods: We recruited 30 pairs of adult male siblings (15 pairs with an ASD endophenotype and 15 pairs without) and focused on four gray matter parameters: cortical volume and three surface-based parameters (cortical thickness, fractal dimension, and sulcal depth [SD]). First, we sought to identify a pattern of an ASD endophenotype, comparing the four parameters. Then, we compared individuals with ASD and their unaffected siblings in the cortical parameters to identify neural correlates for the clinical diagnosis accounting for the difference between TD siblings. Results: A sparse logistic regression with a leave-one-pair-out cross-validation showed the SD as having the highest accuracy for the identification of an ASD endophenotype (73.3%) compared with the other three parameters. A bootstrapping analysis accounting for the difference in the SD between TD siblings showed a significantly large difference between individuals with ASD and their unaffected siblings in six out of 68 regions of interest. Conclusion: This proof-of-concept study suggests that an ASD endophenotype emerges in the SD and that neural bases for ASD diagnosis can be discerned from the endophenotype when accounting for the difference between TD siblings.

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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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Brain functional alterations observed 4-weekly in major depressive disorder following antidepressant treatment

Yamagata B., Yamanaka K., Takei Y., Hotta S., Hirano J., Tabuchi H., Mimura M.

Journal of Affective Disorders （Journal of Affective Disorders） 252 25 - 31 2019年06月

ISSN 01650327

© 2019 Background: Major depressive disorder (MDD) is a heterogeneous condition. Identifying the brain responses to antidepressant treatment is of particular interest as these may represent potential neural networks related to treatment response, forming one aspect of the biological markers of MDD. Near-infrared spectroscopy (NIRS) is suitable for repeated measurements with short intervals because of its noninvasiveness, and can provide detailed time courses of functional alterations in prefrontal regions. Methods: We conducted a 12-week longitudinal study to explore prefrontal hemodynamic changes at 4-week intervals following sertraline treatment in 11 medication-naïve participants with MDD using 52-channel NIRS. Results: While all participants achieved remission after treatment, intra-class correlation coefficient of oxygenated hemoglobin [oxy-Hb] values throughout the 12-week observation was moderate at the spatially and temporally contiguous cluster located in the left inferior frontal and temporal gyri. There was a significant negative correlation between mean [oxy-Hb] values in the significant cluster at 4 weeks and changes in Hamilton Rating Scale for Depression total score from 4 to 8 weeks (r = −0.73, P = 0.011) and from 4 to 12 weeks (r = −0.63, P = 0.039). Limitations: Without healthy controls for comparison, we were unable to fully evaluate whether improvement of [oxy-Hb] activations after treatment in MDD reached normal levels or not. Conclusion: Our NIRS findings of detailed prefrontal hemodynamic alterations over short interval observations such as 4 weeks may have revealed potential trait marker for MDD and biological maker for predicting clinical response to sertraline treatment in MDD.

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