研究者詳細 - 内田　裕之

論文 - 内田　裕之

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The long-term effects of antipsychotic medication on clinical course in schizophrenia

Goff D.C., Falkai P., Fleischhacker W.W., Girgis R.R., Kahn R.M., Uchida H., Zhao J., Lieberman J.A.

American Journal of Psychiatry （American Journal of Psychiatry） 174 （ 9 ） 840 - 849 2017年09月

ISSN 0002-953X

Concerns have been raised that treatment with antipsychotic medication might adversely affect long-term outcomes for people with schizophrenia. The evidence cited for these concerns includes the association of antipsychotic treatment with brain volume reduction and with dopamine receptor sensitization, which might make patients vulnerable to relapse and illness progression. An international group of experts was convened to examine findings from clinical and basic research relevant to these concerns. Little evidence was found to support a negative long-term effect of initial or maintenance antipsychotic treatment on outcomes, compared with withholding treatment. Randomized controlled trials strongly support the efficacy of antipsychotics for the acute treatment of psychosis and prevention of relapse; correlational evidence suggests that early intervention and reduced duration of untreated psychosis might improve longer-term outcomes. Strategies for treatment discontinuation or alternative non-pharmacologic treatment approaches maybenefit a subgroup of patients but may be associated with incremental risk of relapse and require further study, including the development of biomarkers that will enable a precision medicine approach to individualized treatment.

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Resilience and spirituality in patients with depression and their family members

Ozawa Chisa, Suzuki Takefumi, Mizuno Yuya, Tarumi Ryosuke, Yoshida Kazunari, Fujii Kazuhito, Hirano Jinichi, Tani Hideaki, Rubinstein Ellen B., Mimura Masaru, Uchida Hiroyuki

Comprehensive Psychiatry 77 53 - 59 2017年08月

ISSN 0010-440X

Objective The degree and quality of resilience in patients with depression have never been investigated in the context of remission status, spirituality/religiosity, and family members' resilience levels, which was addressed in this study. Methods This cross-sectional study recruited Japanese outpatients with depressive disorder according to ICD-10 and cohabitant family members who were free from psychiatric diagnoses. Resilience was assessed using the 25-item Resilience Scale (RS). Other assessments included the Montgomery-Asberg Depression Rating Scale (MADRS); the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT) and Kasen et al.'s (2012) scale for spirituality/religiosity; and the Rosenberg Self-Esteem Scale (RSES). Results One hundred outpatients with depression (mean ± SD age, 50.8 ± 14.5 years; 44 men; MADRS total score 9.8 ± 9.0) and 36 healthy family members (mean ± SD age, 56.5 ± 15.0 years; 18 men) were included. Symptom severity, attendance at religious/spiritual services, and self-esteem were significantly associated with RS scores in the patient group. RS total scores were significantly higher in remitted patients compared to non-remitted patients (mean ± SD, 112.3 ± 17.1 vs. 84.8 ± 27.7, p < 0.001). No correlation was found in RS total scores between patients and their family members (p = 0.265), regardless of patients' remission status. Conclusions Resilience may be influenced by individual characteristics rather than familial environment; furthermore, self-esteem or spirituality/religiosity may represent reinforcing elements. While caution is necessary in extrapolating these findings to other patient populations, our results suggest that resilience may be considered a state marker in depression.

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Frontal and temporal cortical functional recovery after electroconvulsive therapy for depression

Hirano Jinichi, Takamiya Akihiro, Yamagata Bun, Hotta Syogo, Miyasaka Yukiko, Pu Shenghong, Iwanami Akira, Uchida Hiroyuki, Mimura Masaru

Journal of Psychiatric Research 91 26 - 35 2017年08月

ISSN 0022-3956

While the efficacy and tolerability of electroconvulsive therapy (ECT) for depression has been well established, the acute effects of ECT on brain function remain unclear. Particularly, although cognitive dysfunction has been consistently observed after ECT, little is known about the extent and time course of ECT-induced brain functional changes, as observed during cognitive tasks. Considering the acute antidepressant effects of ECT on depression, aberrant brain functional responses during cognitive tasks in patients with depression may improve immediately after this treatment. To clarify changes in cortical functional responses to cognitive tasks following ECT, we used task-related functional near-infrared spectroscopy (NIRS) to assess 30 patients with major depressive disorder or bipolar depression before and after an ECT series, as well as 108 healthy controls. Prior to ECT, patients exhibited significantly smaller [oxy-Hb] values in the bilateral frontal cortex during a letter verbal fluency task (VFT) compared with healthy controls. We found a significant increase in [oxy-Hb] values in the bilateral frontal cortex during the VFT after ECT in the patient group. A decrease in depression severity was significantly correlated with an increase in [oxy-Hb] values in the right ventrolateral prefrontal cortex following ECT. This is the first NIRS study to evaluate brain functional changes before vs. after ECT. Impaired functional responses, observed during the cognitive task in depressed patients, were normalized after ECT. Thus, recovery from abnormal functional responses to cognitive tasks in the frontal brain regions may be associated with the acute therapeutic effects of ECT for depression.

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Frontal and temporal cortical functional recovery after electroconvulsive therapy for depression: A longitudinal functional near-infrared spectroscopy study

Hirano J., Takamiya A., Yamagata B., Hotta S., Miyasaka Y., Pu S., Iwanami A., Uchida H., Mimura M.

Journal of Psychiatric Research （Journal of Psychiatric Research） 91 26 - 35 2017年08月

ISSN 00223956

© 2017 Elsevier Ltd While the efficacy and tolerability of electroconvulsive therapy (ECT) for depression has been well established, the acute effects of ECT on brain function remain unclear. Particularly, although cognitive dysfunction has been consistently observed after ECT, little is known about the extent and time course of ECT-induced brain functional changes, as observed during cognitive tasks. Considering the acute antidepressant effects of ECT on depression, aberrant brain functional responses during cognitive tasks in patients with depression may improve immediately after this treatment. To clarify changes in cortical functional responses to cognitive tasks following ECT, we used task-related functional near-infrared spectroscopy (NIRS) to assess 30 patients with major depressive disorder or bipolar depression before and after an ECT series, as well as 108 healthy controls. Prior to ECT, patients exhibited significantly smaller [oxy-Hb] values in the bilateral frontal cortex during a letter verbal fluency task (VFT) compared with healthy controls. We found a significant increase in [oxy-Hb] values in the bilateral frontal cortex during the VFT after ECT in the patient group. A decrease in depression severity was significantly correlated with an increase in [oxy-Hb] values in the right ventrolateral prefrontal cortex following ECT. This is the first NIRS study to evaluate brain functional changes before vs. after ECT. Impaired functional responses, observed during the cognitive task in depressed patients, were normalized after ECT. Thus, recovery from abnormal functional responses to cognitive tasks in the frontal brain regions may be associated with the acute therapeutic effects of ECT for depression.

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Predicting relapse with individual residual symptoms in major depressive disorder: a reanalysis of the STAR*D data

Sakurai H., Suzuki T., Yoshimura K., Mimura M., Uchida H.

Psychopharmacology （Psychopharmacology） 234 （ 16 ） 2453 - 2461 2017年08月

ISSN 00333158

© 2017, Springer-Verlag Berlin Heidelberg. Background: Residual symptoms are detrimental to prognosis in major depressive disorder (MDD); however, little is known about the contribution of each residual symptom in predicting outcomes. The objective of this analysis was to identify which individual symptoms, based on self-report and clinician interview, could predict subsequent relapse. Methods: The data of 1133 outpatients with nonpsychotic MDD who entered a 12-month naturalistic follow-up phase after achieving remission with level 1 treatment (i.e., citalopram for up to 14 weeks) and had at least one post-baseline contact in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial were analyzed. Specific residual symptoms in the 16-item Quick Inventory of Depressive Symptomatology, self-report (QIDS-SR16) and clinician rating (QIDS-C16), at the follow-up entry that predicted relapse were identified, using a Cox proportional hazards model. Results: The following three QIDS-SR16 symptoms were significantly associated with subsequent relapse: restlessness (HR = 1.197, p = 0.018), hypersomnia (HR = 1.190, p = 0.009), and weight change (HR = 1.127, p = 0.041). On the other hand, the following three symptoms in the QIDS-C16 at the follow-up entry were significantly associated with relapse in the follow-up phase: restlessness (HR = 1.328, p = 0.001), sleep onset insomnia (HR = 1.129, p = 0.047), and weight change (HR = 1.125, p = 0.045). Limitations: The original trial was not designed to evaluate the issue addressed herein. Individual symptoms may be associated with each other and functional status was not addressed. Conclusions: Some residual symptoms, including restlessness, insomnia, and weight change, may help better identify patients with MDD vulnerable to relapse. Contribution of individual residual symptoms to subsequent relapse was similar between self-report and clinician-rated symptoms.

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Resilience and spirituality in patients with depression and their family members: A cross-sectional study

Ozawa C., Suzuki T., Mizuno Y., Tarumi R., Yoshida K., Fujii K., Hirano J., Tani H., Rubinstein E.B., Mimura M., Uchida H.

Comprehensive Psychiatry （Comprehensive Psychiatry） 77 53 - 59 2017年08月

ISSN 0010440X

© 2017 Elsevier Inc. Objective The degree and quality of resilience in patients with depression have never been investigated in the context of remission status, spirituality/religiosity, and family members' resilience levels, which was addressed in this study. Methods This cross-sectional study recruited Japanese outpatients with depressive disorder according to ICD-10 and cohabitant family members who were free from psychiatric diagnoses. Resilience was assessed using the 25-item Resilience Scale (RS). Other assessments included the Montgomery-Asberg Depression Rating Scale (MADRS); the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT) and Kasen et al.'s (2012) scale for spirituality/religiosity; and the Rosenberg Self-Esteem Scale (RSES). Results One hundred outpatients with depression (mean ± SD age, 50.8 ± 14.5 years; 44 men; MADRS total score 9.8 ± 9.0) and 36 healthy family members (mean ± SD age, 56.5 ± 15.0 years; 18 men) were included. Symptom severity, attendance at religious/spiritual services, and self-esteem were significantly associated with RS scores in the patient group. RS total scores were significantly higher in remitted patients compared to non-remitted patients (mean ± SD, 112.3 ± 17.1 vs. 84.8 ± 27.7, p < 0.001). No correlation was found in RS total scores between patients and their family members (p = 0.265), regardless of patients' remission status. Conclusions Resilience may be influenced by individual characteristics rather than familial environment; furthermore, self-esteem or spirituality/religiosity may represent reinforcing elements. While caution is necessary in extrapolating these findings to other patient populations, our results suggest that resilience may be considered a state marker in depression.

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Prediction Model of Serum Lithium Concentrations

Yoshida K., Uchida H., Suzuki T., Watanabe M., Yoshino N., Houchi H., Mimura M., Fukuoka N.

Pharmacopsychiatry （Pharmacopsychiatry） 51 （ 3 ） 82 - 88 2017年07月

ISSN 0176-3679

© Georg Thieme Verlag KG Stuttgart.New York. Introduction Therapeutic drug monitoring is necessary for lithium, but clinical application of several prediction strategies is still limited because of insufficient predictive accuracy. We herein proposed a suitable model, using creatinine clearance (CLcr)-based lithium clearance (Li-CL). Methods Patients receiving lithium provided the following information: serum lithium and creatinine concentrations, time of blood draw, dosing regimen, concomitant medications, and demographics. Li-CL was calculated as a daily dose per trough concentration for each subject, and the mean of Li-CL/CLcr was used to estimate Li-CL for another 30 subjects. Serum lithium concentrations at the time of sampling were estimated by 1-compartment model with Li-CL, fixed distribution volume (0.79 L/kg), and absorption rate (1.5/hour) in the 30 subjects. Results One hundred thirty-one samples from 82 subjects (44 men; mean±standard deviation age: 51.4±16.0 years; body weight: 64.6±13.8 kg; serum creatinine: 0.78±0.20 mg/dL; dose of lithium: 680.2±289.1 mg/day) were used to develop the pharmacokinetic model. The mean±standard deviation (95% confidence interval) of absolute error was 0.13±0.09 (0.10-0.16) mEq/L. Discussion Serum concentrations of lithium can be predicted from oral dosage with high precision, using our prediction model.

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Immediate vs Gradual Discontinuation in Antipsychotic Switching

Takeuchi Hiroyoshi, Kantor Navot, Uchida Hiroyuki, Suzuki Takefumi, Remington Gary

Schizophrenia Bulletin 43 （ 4 ） 862 - 871 2017年07月

ISSN 0586-7614

Background: Antipsychotic switching is routine in clinical practice, although it remains unclear which is the preferable switching method: immediate discontinuation of the current antipsychotic or a gradual tapering approach. The first strategy has been implicated in rebound/withdrawal symptoms and emergence/exacerbation of symptoms, whereas the gradual approach is thought to pose a risk of additive or synergistic side effects if employed in the context of a crossover approach. Methods: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were systematically searched. Randomized controlled trials examining immediate vs gradual antipsychotic discontinuation in antipsychotic switching in patients with schizophrenia and/or schizoaffective disorder were selected. Data on clinical outcomes, including study discontinuation, psychopathology, extrapyramidal symptoms, and treatment-emergent adverse events, were extracted. Results: A total of 9 studies involving 1416 patients that met eligibility criteria were included in the meta-analysis. No significant differences in any clinical outcomes were found between the 2 approaches (all Ps >.05). Sensitivity analyses revealed that the findings remained unchanged in the studies where switching to aripiprazole was performed or where immediate initiation of the next antipsychotic was adopted, while some significant differences were observed in switching to olanzapine or ziprasidone. Conclusions: These findings indicate that either immediate or gradual discontinuation of the current antipsychotic medication represents a viable treatment option. Clinicians are advised to choose an antipsychotic switching strategy according to individual patient needs. This said, immediate discontinuation may be advantageous both for simplicity and because a stalled cross-titration process in antipsychotic switching could end up in antipsychotic polypharmacy.

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A Population approach to guide amisulpride dose adjustments in older patients with Alzheimer's disease

Reeves S., Bertrand J., McLachlan E., D'Antonio F., Brownings S., Nair A., Greaves S., Smith A., Dunn J.T., Marsden P., Kessler R., Uchida H., Taylor D., Howard R.

Journal of Clinical Psychiatry （Journal of Clinical Psychiatry） 78 （ 7 ） e844 - e851 2017年07月

ISSN 0160-6689

© 2017 Physicians Postgraduate Press, Inc. Objective: We have previously reported high dopamine D2/3 receptor occupancies at low amisulpride concentrations in older people with Alzheimer's disease (AD), during off-label treatment of AD-related psychosis. This post hoc analysis explored pharmacokinetic (concentration) and pharmacodynamic (prolactin, D2/3 occupancy) contributions to symptom reduction and extrapyramidal side effects (EPS) to inform AD-specific dose adjustments. Methods: Population pharmacokinetic-pharmacodynamic models were developed by combining pharmacokinetic data from a phase 1 study in 20 healthy older people with pharmacokinetic prolactin, [18F]fallypride D2/3 receptor imaging, and clinical outcome data from 28 older patients prescribed open amisulpride (25-75 mg/d) to treat AD-related psychosis. Model predictions were used to simulate dose-response and dose-EPS. Results: Symptom reduction (delusions) was associated with amisulpride concentration (P = 1.3e-05) and D2/3 occupancy (P <.01, caudate, putamen, thalamus). Model predictions suggested that across concentrations of 40-100 ng/mL, and occupancies of 40% to 70% in the caudate and thalamus and 30% to 60% in the putamen, there was a 50% to 90% probability of response and < 30% probability of EPS. Simulations, based on concentration-delusions and concentration-EPS model outputs, showed that 50 mg/d of amisulpride was the appropriate dose to achieve this target range in those aged > 75 years; increasing the dose to 75 mg/d increased the risk of EPS, particularly in those aged > 85 years of low body weight. Conclusions: These findings argue strongly for the consideration of age- and weight-based dose adjustments in older patients with AD-related psychosis and indicate that 50 mg/d of amisulpride may be both the minimal clinically effective dose and, in those aged > 75 years, the maximally tolerated dose.

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Dietary nitrite supplementation attenuates cardiac remodeling in l-NAME-induced hypertensive rats.

Sonoda K, Ohtake K, Uchida H, Ito J, Uchida M, Natsume H, Tamada H, Kobayashi J

Nitric oxide : biology and chemistry 67 1 - 9 2017年07月

ISSN 1089-8603

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Immediate vs Gradual Discontinuation in Antipsychotic Switching: A Systematic Review and Meta-analysis

Takeuchi H., Kantor N., Uchida H., Suzuki T., Remington G.

Schizophrenia Bulletin （Schizophrenia Bulletin） 43 （ 4 ） 862 - 871 2017年07月

ISSN 05867614

© The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. Background: Antipsychotic switching is routine in clinical practice, although it remains unclear which is the preferable switching method: immediate discontinuation of the current antipsychotic or a gradual tapering approach. The first strategy has been implicated in rebound/withdrawal symptoms and emergence/exacerbation of symptoms, whereas the gradual approach is thought to pose a risk of additive or synergistic side effects if employed in the context of a crossover approach. Methods: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were systematically searched. Randomized controlled trials examining immediate vs gradual antipsychotic discontinuation in antipsychotic switching in patients with schizophrenia and/or schizoaffective disorder were selected. Data on clinical outcomes, including study discontinuation, psychopathology, extrapyramidal symptoms, and treatment-emergent adverse events, were extracted. Results: A total of 9 studies involving 1416 patients that met eligibility criteria were included in the meta-analysis. No significant differences in any clinical outcomes were found between the 2 approaches (all Ps >.05). Sensitivity analyses revealed that the findings remained unchanged in the studies where switching to aripiprazole was performed or where immediate initiation of the next antipsychotic was adopted, while some significant differences were observed in switching to olanzapine or ziprasidone. Conclusions: These findings indicate that either immediate or gradual discontinuation of the current antipsychotic medication represents a viable treatment option. Clinicians are advised to choose an antipsychotic switching strategy according to individual patient needs. This said, immediate discontinuation may be advantageous both for simplicity and because a stalled cross-titration process in antipsychotic switching could end up in antipsychotic polypharmacy.

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Immediate effect of subliminal priming with positive reward stimuli on standing balance in healthy individuals: A randomized controlled trial.

Aoyama Y, Uchida H, Sugi Y, Kawakami A, Fujii M, Kiso K, Kono R, Takebayashi T, Hirao K

Medicine 96 （ 28 ） e7494 2017年07月

ISSN 0025-7974

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Lack of Early Improvement with Antipsychotics is a Marker for Subsequent Nonresponse in Behavioral and Psychological Symptoms of Dementia: Analysis of CATIE-AD Data

Yoshida K., Roberts R., Suzuki T., Lebowitz B., Reeves S., Howard R., Abe T., Mimura M., Uchida H.

American Journal of Geriatric Psychiatry （American Journal of Geriatric Psychiatry） 25 （ 7 ） 708 - 716 2017年07月

ISSN 10647481

© 2017 American Association for Geriatric Psychiatry Objective Prediction of response or nonresponse to antipsychotics is especially important in patients with behavioral and psychological symptoms of dementia (BPSD) in whom antipsychotic exposure increases risks of death. This study examined whether the presence or absence of early improvement of BPSD with antipsychotics is associated with subsequent response or nonresponse. Methods In a post-hoc analysis of the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) study (2001–2004) (clinicaltrials.gov; NCT00015548) in 45 U.S. sites, 245 subjects (olanzapine, N = 90; quetiapine, N = 81; risperidone, N = 74) with a DSM-IV diagnosis of dementia of the Alzheimer type who presented with a score of 1 or more in the Brief Psychiatric Rating Scale (BPRS) at baseline (phase I of CATIE-AD) were randomly assigned to treatment with olanzapine, quetiapine, risperidone, or placebo in a double-blind manner. Associations were examined between response at week 8 and demographic and clinical characteristics, including BPRS total score reduction at week 2, using logistic regression analyses. Prediction performance of binary classification (presence or absence) of improvement or no improvement at week 2 for response at week 8 was examined. Results BPRS total score reduction at week 2 (mean percentage score reduction: 12.6%) was significantly associated with response at week 8 (odds ratio: 1.18; 95% CI: 1.11–1.26). The 5% score reduction cut-off at week 2 showed the highest accuracy (0.71), with sensitivity, specificity, and positive and negative predictivevalues of 0.76, 0.65, 0.69, and 0.72, respectively. Conclusion Lack of even a very small early improvement with antipsychotic treatment may be a marker of subsequent nonresponse in BPSD.

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Identification of common words to improve self-confidence in Japanese students with subthreshold depression.

Takahashi K, Takada K, Inoue A, Ohno S, Tanigawa M, Ishihara Y, Uchida H, Hirao K

International journal of adolescent medicine and health 31 （ 3 ） 2017年06月

ISSN 0334-0139

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統合失調症における抗精神病薬のドパミンD2受容体遮断と症状変動

内田裕之, 小泉輝樹, Bies Robert R., Pollock Bruce G., 鈴木健文

臨床薬理の進歩（(公財)臨床薬理研究振興財団）（ 38 ） 96 - 103 2017年06月

ISSN 0914-4366

統合失調症患者27例(男性19名、平均48.1±15.5歳)を対象とし、幻聴体験の時刻、内容、各時間帯(3時間毎)の重症度を記録するように依頼した。陽性・陰性症状評価尺度、機能の全体的評定、Simpson Angus評価尺度、Barnesアカシジア尺度、異常不随意運動評価尺度を用いて精神症状および抗精神病薬の副作用を評価した。リスペリドン、オランザピン、9水酸化リスペリドンの血中薬物濃度を任意の2時点で計測した。殆どが入院患者(26例)で、罹病期間が30年以上の長期経過を取った患者が大半を占めた。幻聴の頻度は、ドパミンD2受容体遮断ピーク時間帯とトラフ時間帯で有意差はなかった。各時間帯に幻聴を経験した患者の割合は、18〜21時の時間帯で有意に高かった。

Predicting relapse with individual residual symptoms in major depressive disorder

Sakurai Hitoshi, Suzuki Takefumi, Yoshimura Kimio, Mimura Masaru, Uchida Hiroyuki

Psychopharmacology 1 - 9 2017年05月

ISSN 0033-3158

Background: Residual symptoms are detrimental to prognosis in major depressive disorder (MDD); however, little is known about the contribution of each residual symptom in predicting outcomes. The objective of this analysis was to identify which individual symptoms, based on self-report and clinician interview, could predict subsequent relapse. Methods: The data of 1133 outpatients with nonpsychotic MDD who entered a 12-month naturalistic follow-up phase after achieving remission with level 1 treatment (i.e., citalopram for up to 14 weeks) and had at least one post-baseline contact in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial were analyzed. Specific residual symptoms in the 16-item Quick Inventory of Depressive Symptomatology, self-report (QIDS-SR₁₆) and clinician rating (QIDS-C₁₆), at the follow-up entry that predicted relapse were identified, using a Cox proportional hazards model. Results: The following three QIDS-SR₁₆ symptoms were significantly associated with subsequent relapse: restlessness (HR = 1.197, p = 0.018), hypersomnia (HR = 1.190, p = 0.009), and weight change (HR = 1.127, p = 0.041). On the other hand, the following three symptoms in the QIDS-C₁₆ at the follow-up entry were significantly associated with relapse in the follow-up phase: restlessness (HR = 1.328, p = 0.001), sleep onset insomnia (HR = 1.129, p = 0.047), and weight change (HR = 1.125, p = 0.045). Limitations: The original trial was not designed to evaluate the issue addressed herein. Individual symptoms may be associated with each other and functional status was not addressed. Conclusions: Some residual symptoms, including restlessness, insomnia, and weight change, may help better identify patients with MDD vulnerable to relapse. Contribution of individual residual symptoms to subsequent relapse was similar between self-report and clinician-rated symptoms.

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Vestibular stimulation improves insight into illness in schizophrenia spectrum disorders

Gerretsen P., Pothier D., Falls C., Armstrong M., Balakumar T., Uchida H., Mamo D., Pollock B., Graff-Guerrero A.

Psychiatry Research （Psychiatry Research） 251 333 - 341 2017年05月

ISSN 0165-1781

© 2017 Elsevier Ireland Ltd Impaired insight into illness (IMP-INS) is common among individuals with schizophrenia spectrum disorders (SSD), contributing to medication nonadherence and poor clinical outcomes. Caloric vestibular simulation (CVS) is typically used to assess peripheral vestibular system function. Left cold CVS is also a transiently effective treatment for IMP-INS and hemineglect secondary to right brain hemisphere stroke, and possibly for IMP-INS and mood stabilization in patients with SSD. Participants with SSD and moderate-to-severe IMP-INS participated in an exploratory double blind, crossover, randomized controlled study of the effects of CVS on IMP-INS. Participants sequentially received all experimental conditions—left cold (4 °C), right cold, and body temperature/sham CVS—in a random order. Repeated measures ANOVA were performed to compare changes in IMP-INS, mood and positive symptom severity pre and 30 min post CVS. A significant interaction was found between CVS condition, time, and body temperature nystagmus peak slow phase velocity (PSPV) for IMP-INS, indicating that single session left cold CVS transiently improved IMP-INS while right cold CVS may have worsened IMP-INS, particularly in participants with greater vestibular reactivity (i.e. higher PSPV) to body temperature CVS. The procedure's effectiveness is attributed to stimulation of underactive right hemisphere circuits via vestibular nuclei projections to the contralateral hemisphere.

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Insight into illness and its relationship to illness severity, cognition and estimated antipsychotic dopamine receptor occupancy in schizophrenia

Gerretsen Philip, Takeuchi Hiroyoshi, Ozzoude Miracle, Graff-Guerrero Ariel, Uchida Hiroyuki

Psychiatry Research 251 20 - 25 2017年05月

ISSN 0165-1781

Little is known about the influence of D₂ receptor occupancy on impaired insight into illness (III)—a core feature of schizophrenia. III is associated with illness severity and cognitive dysfunction. Comparably, supratherapeutic D₂ receptor occupancy can impair cognition. However, it is unclear how illness severity, cognition, and D₂ receptor occupancy interact to influence III in schizophrenia. The aim of this study was to explore the influence of antipsychotic dose reduction on the relationships of illness severity and cognition to III. III was assessed at baseline and 28 weeks post-antipsychotic dose reduction in 16 participants with schizophrenia and plasma antipsychotic concentrations. III was assessed primarily with the Schedule for the Assessment of Insight–Japanese version, and secondarily with the Positive and Negative Syndrome Scale item G12. Correlation and regression analyses were performed to explore III's relationship to illness severity, cognition, and estimated D₂ receptor occupancy (Est.D₂). Cognition and Est.D₂ predicted III at baseline. At 28 weeks post-reduction, illness severity and Est.D₂ predicted III. Our findings suggest a complex relationship may exist among III, illness severity, cognition and Est.D₂. At higher D₂ receptor occupancies, III is influenced by cognitive dysfunction, whereas, at lower occupancies, illness severity has a stronger effect on III.

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Representativeness of clinical PET study participants with schizophrenia

Kirino So, Suzuki Takefumi, Takeuchi Hiroyoshi, Mimura Masaru, Uchida Hiroyuki

Journal of Psychiatric Research 88 72 - 79 2017年05月

ISSN 0022-3956

While positron emission tomography (PET) studies have provided invaluable data on antipsychotic effects, selection bias remains a serious concern. A systematic review of PET studies that measured dopamine D₂ receptor blockade with antipsychotics was conducted to examine their inclusion/exclusion criteria, using PubMed, EMBASE, and ClinicalTrials.gov (last search, September 2016). PET studies were included if they measured D₂ receptor occupancy in patients with schizophrenia and included introduction of antipsychotic treatment or antipsychotic regimen change in a systematic manner. Twenty-six studies were identified. Age limit was included in 13 studies; one study solely included geriatric patients while others targeted younger adults. Eleven, 6, and 3 studies specifically targeted clinically stable patients, patients with severe psychopathology, and antipsychotic-free patients, respectively. Nineteen and 18 studies excluded patients with physical comorbidity and substance abuse, respectively. As a result, the mean age of subjects ranged from 23 to 42 years when one study that targeted geriatric patients was excluded. Mean Positive and Negative Syndrome Scale total scores ranged from 54 to 95. No comparison active-drug or placebo arm was employed in 24 studies. Blind assessment of symptomatology was performed in 5 studies. In general, subjects participating in clinical PET studies were relatively young, presented with mild symptomatology, and were free from substance abuse or physical comorbidities. These characteristics need to be taken into account when clinical PET data are interpreted. On the other hand, it should also be noted that this study was only qualitative and conservative interpretation is necessary for possibility of subjective bias.

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Insight into illness and its relationship to illness severity, cognition and estimated antipsychotic dopamine receptor occupancy in schizophrenia: An antipsychotic dose reduction study

Gerretsen P., Takeuchi H., Ozzoude M., Graff-Guerrero A., Uchida H.

Psychiatry Research （Psychiatry Research） 251 20 - 25 2017年05月

ISSN 01651781

© 2017 Elsevier Ireland Ltd Little is known about the influence of D2 receptor occupancy on impaired insight into illness (III)—a core feature of schizophrenia. III is associated with illness severity and cognitive dysfunction. Comparably, supratherapeutic D2 receptor occupancy can impair cognition. However, it is unclear how illness severity, cognition, and D2 receptor occupancy interact to influence III in schizophrenia. The aim of this study was to explore the influence of antipsychotic dose reduction on the relationships of illness severity and cognition to III. III was assessed at baseline and 28 weeks post-antipsychotic dose reduction in 16 participants with schizophrenia and plasma antipsychotic concentrations. III was assessed primarily with the Schedule for the Assessment of Insight–Japanese version, and secondarily with the Positive and Negative Syndrome Scale item G12. Correlation and regression analyses were performed to explore III's relationship to illness severity, cognition, and estimated D2 receptor occupancy (Est.D2). Cognition and Est.D2 predicted III at baseline. At 28 weeks post-reduction, illness severity and Est.D2 predicted III. Our findings suggest a complex relationship may exist among III, illness severity, cognition and Est.D2. At higher D2 receptor occupancies, III is influenced by cognitive dysfunction, whereas, at lower occupancies, illness severity has a stronger effect on III.

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