研究者詳細 - 菊地　俊暁

論文 - 菊地　俊暁

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Dynamic neural network modulation associated with rumination in major depressive disorder: a prospective observational comparative analysis of cognitive behavioral therapy and pharmacotherapy

Katayama N., Shinagawa K., Hirano J., Kobayashi Y., Nakagawa A., Umeda S., Kamiya K., Tajima M., Amano M., Nogami W., Ihara S., Noda S., Terasawa Y., Kikuchi T., Mimura M., Uchida H.

Translational Psychiatry 15 （ 1 ） 2025年12月

Cognitive behavioral therapy (CBT) and pharmacotherapy are primary treatments for major depressive disorder (MDD). However, their differential effects on the neural networks associated with rumination, or repetitive negative thinking, remain poorly understood. This study included 135 participants, whose rumination severity was measured using the rumination response scale (RRS) and whose resting brain activity was measured using functional magnetic resonance imaging (fMRI) at baseline and after 16 weeks. MDD patients received either standard CBT based on Beck’s manual (n = 28) or pharmacotherapy (n = 32). Using a hidden Markov model, we observed that MDD patients exhibited increased activity in the default mode network (DMN) and decreased occupancies in the sensorimotor and central executive networks (CEN). The DMN occurrence rate correlated positively with rumination severity. CBT, while not specifically designed to target rumination, reduced DMN occurrence rate and facilitated transitions toward a CEN-dominant brain state as part of broader therapeutic effects. Pharmacotherapy shifted DMN activity to the posterior region of the brain. These findings suggest that CBT and pharmacotherapy modulate brain network dynamics related to rumination through distinct therapeutic pathways.

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Long-term effectiveness of vortioxetine on achievement of personal goals and work productivity in patients with major depressive disorder: The VGOAL-J study

Watanabe K., Sumiyoshi T., Kato M., Kikuchi T., Moriguchi Y., Åström D.O., Christensen M.C.

Journal of Affective Disorders Reports 21 2025年07月

Background: The long-term effectiveness of vortioxetine for facilitating progress toward personal recovery goals and improving productivity at work was assessed in patients with major depressive disorder (MDD). Methods: Single-arm, prospective, 24-week cohort study in employed patients with MDD initiating treatment with vortioxetine (n = 121) in outpatient settings in Japan. The Goal Attainment Scale for Depression (GAS-D) was used to evaluate progress toward personal recovery goals. At baseline, a combination of patient-defined and pre-specified goals was established collaboratively with the treating psychiatrist, followed by longitudinal assessments at baseline and weeks 4, 8, 12, and 24. Work-related productivity was assessed using the Work Productivity and Activity Impairment (WPAI) questionnaire. Co-primary endpoints were the proportion of patients achieving their pre-specified personal recovery goals at week 12 and the change in work productivity from baseline. Results: In all, 45/107 patients (42.1%) had achieved their personal recovery goals at week 12, increasing to 62/100 (62.0%) at week 24. Significant improvement was observed across all WPAI domains (i.e., absenteeism, presenteeism, productivity loss, and activity impairment) at week 24. Depressive symptoms, global patient functioning, emotional and cognitive symptoms, cognitive performance, and quality of life also significantly improved over the 24 weeks of follow-up. At week 24, 80/102 patients (78.4%) remained on vortioxetine; 49 of these patients (61.3%) were receiving vortioxetine 20 mg/day. Limitations: Open-label study. Conclusions: Vortioxetine was found to be effective in helping to achieve personal recovery goals and in enhancing workplace productivity over the 6-month study period in patients with MDD. Trial registration: Japan Primary Registries Network: JRCT1031210200.

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Impact of Emotional Blunting on Patient Social Function and Depressive Symptoms: A Post Hoc Analysis of a Web-Based Survey in Japanese Patients with Major Depressive Disorder

Kikuchi T., Iga J.I., Hattori A., Tokuda F., Moriguchi Y., Hoshino T.

Neuropsychiatric Disease and Treatment 21 841 - 854 2025年

Background: Emotional blunting (EB), defined as a flattening of emotions and emotional indifference, is reported by many patients with major depressive disorder (MDD) taking antidepressants. Severity of EB correlates with depressive symptoms, as well as deficits in social function, anxiety and health-related quality of life. However, awareness and understanding of EB and its impact on treatment of MDD remain poorly understood. Methods: This was a post hoc analysis of data from a web-based survey of 3376 adults with MDD in Japan. The primary endpoint was the correlation between total and subdomain scores of the Oxford Depression Questionnaire (ODQ; a validated instrument to assess EB) and total and individual domain/item scores of the Work and Social Adjustment Scale (WSAS) and Patient Health Questionnaire 9-item (PHQ-9). The secondary endpoint explored which patients had a discrepancy between EB symptoms (assessed by the ODQ) and their own evaluation of EB (using a validated screening question). Results: There was a moderate correlation between the ODQ total score and the WSAS total score (Spearman’s rank correlation coefficient [r<inf>s</inf> ] = 0.578) and a strong correlation between the ODQ total score and PHQ-9 total score (r<inf>s</inf> = 0.670). Multiple regression analyses showed that the ODQ subdomains “not caring” (NC) and “reduction in positive emotions” (PR) had the greatest impact on both the WSAS total score (partial regression coefficients = 1.034 and 0.501, respectively) and PHQ-9 total score (partial regression coefficients = 0.548 and 0.592, respectively). A higher proportion of men (versus women) and unemployed individuals (versus employed individuals) underestimated their EB severity compared with their ODQ score. Conclusion: The ODQ subdomains of NC and PR are important factors when evaluating the impact of EB on social function and severity of depressive symptoms in patients with MDD. Physicians should assess EB symptoms for each patient, considering the patient’s background.

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Network meta-analysis of the effectiveness of psychotherapies with or without medication for treating adult depression

Fukumori M., Kikuchi T., Zhou Y., Hattori S., Kudo T.

Acta Neuropsychiatrica 36 （ 6 ） 423 - 437 2024年12月

ISSN 09242708

Objective: To ascertain whether psychotherapies combined with medication are more efficacious than those without medication and determine which combinations yield the best results. Methods: We conducted a network meta-analysis of randomised controlled trials (RCTs) comparing behavioural activation (BA), psychoanalytic/psychodynamic psychotherapy (DYN), interpersonal psychotherapy (IPT), individual face-to-face cognitive behavioural therapy (CBT (ftf)), group cognitive behavioural therapy (gCBT), and computerised or internet cognitive behavioural therapy (iCBT) with each other, or with treatment-as-usual (TAU) and wait list control (WLC) among adults formally diagnosed with depression. The psychotherapy arms were categorised as either psychotherapy alone or psychotherapy combined with medication (+ p). Treatment efficacy was assessed based on depression severity. We used a random-effects model to conduct a pairwise meta-analysis. Results: A total of 100 RCTs with 9,873 participants were included. The most common treatment was CBT (ftf) alone. All treatment arms were compared with TAU. Most psychotherapies combined with medication were superior to psychotherapy alone. In the subgroup analyses according to the baseline severity of depression, most psychotherapies combined with medication were more effective than psychotherapy alone in moderate-to-severe depression, whereas in mild depression, such differences were not observed. Among psychotherapies with medication, gCBT + p was significantly more effective than TAU and other psychotherapies in both the main and subgroup analyses. Conclusion: The efficacy of depression treatment varied depending on the severity of the depressive condition. Notably, gCBT + p was identified as the most effective approach for treating adult depression.

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Gender differences and mental distress during COVID-19: a cross-sectional study in Japan

Kanata T., Takeda K., Fujii T., Iwata R., Hiyoshi F., Iijima Y., Nakao T., Murayama K., Watanabe K., Kikuchi T., Mimura M., Yoshimi A., Hishimoto A., Hirata H., Ozaki N., Kito S., Kuga H., Oba M., Oi H., Nakagome K.

BMC Psychiatry 24 （ 1 ） 2024年12月

Background: To identify risk factors for mental distress and investigate whether the factors were different between men and women during the coronavirus disease 2019 (COVID-19), using KOKOROBO data, which is an online platform that aims to facilitate access to mental health services. Methods: We used baseline data on KOKOROBO users 13 years of age or older in Japan who accessed it from October 11, 2021, to April 6, 2023, excluding those receiving treatment for mental health problems. Global severity, based on the most severe measure on Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Insomnia Severity Index (ISI), was analyzed using multivariable logistic regression with baseline characteristics for each gender, and for under 30 and 30 years of age or older in women. We conducted the same analysis of suicidal ideation for each gender. Results: In the 686 men and 1274 women, 117 (17.1%) and 100 (7.8%) had minimal global severity respectively, and the rest suffered from mental distress to some extent. For women, ages under 30 years (adjusted OR (aOR): 0.352, 95%CI: 0.231–0.539, P < 0.001), marriage (aOR: 0.453, 95%CI: 0.274–0.746, P = 0.002), and concerns about COVID-19 infection were associated with global severity, while having children (aOR: 0.509, 95% CI: 0.284–0.909, P = 0.023) and decrease of going out during the COVID-19 pandemic had a protective effect on global severity and suicidal ideation for men, respectively. Living with family was a risk factor for mental distress in unmarried women over 30 years of age. Less communication with family or others and responding to the questionnaire late at night (00:00–05:59) were associated with severe global severity in both genders. Conclusions: Age, living arrangement, marriage, having children, concerns about COVID-19 infection, and lifestyle changes during the COVID-19 pandemic had gender-specific effects on mental distress, while frequent communication and regular life rhythm maintained mental health in both genders. Young women and, unmarried middle-aged women living with their families tended to experience mental distress during the COVID-19 pandemic. Trial registration: The Ethics Committee of the National Center of Neurology and Psychiatry approved this study (approval number B2020141) on April 15, 2021.

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A web-based survey on the occurrence of emotional blunting in patients with major depressive disorder in Japan: Patient perceptions and attitudes

Kikuchi T., Iga J.i., Oosawa M., Hoshino T., Moriguchi Y., Izutsu M.

Neuropsychopharmacology Reports 44 （ 2 ） 321 - 332 2024年06月

Aims: To determine the prevalence and impact of emotional blunting (EB) in patients with major depressive disorder (MDD) in Japan, and identify treatment needs for EB using patients' perceptions and attitudes. Methods: Eligible patients in Japan (aged 18–59 years) who reported a diagnosis of MDD and antidepressant medication use for >3 months were eligible to complete an online survey. The primary outcome was the prevalence of EB, self-reported using a validated screening question. Secondary outcomes included the correlation between EB symptoms (measured by the Oxford Depression Questionnaire [ODQ]) and scores on the Patient Health Questionnaire 9-item (PHQ-9), Generalized Anxiety Disorder 7-item (GAD-7), Work and Social Adjustment Scale (WSAS), and the EuroQol 5-Dimension 5-Levels questionnaire (EQ-5D-5L). Descriptive questions were used to explore patients' perceptions and attitudes toward EB. Results: In total, 3376 patients were included in the analysis (56% male; 48% aged 50–59 years). Overall, 67.1% of patients self-reported symptoms of EB, with 10% rating these as severe. The mean (SD) ODQ total score was 78.2 (21.5), which increased with worsening EB symptoms. There were correlations between ODQ total scores and the PHQ-9, GAD-7, WSAS, and EQ-5D-5L scores (correlation coefficients: 0.67, 0.55, 0.56, −0.51, respectively; all p < 0.0001). Descriptive analyses showed that one-third of patients reporting EB symptoms did not tell their physician, with two-thirds finding these symptoms distressing and likely to affect recovery. Conclusion: EB is an important clinical issue in Japan that needs to be considered alongside functional recovery when managing treatment of patients with MDD.

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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 78 （ 4 ） 220 - 228 2024年04月

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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Conversation Analysis of Remote Dialogue System for Mental Health Interventions

Yi S., Kikuchi T., Yamasaki T.

Lecture Notes in Computer Science Including Subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics 14975 LNCS 278 - 291 2024年

ISSN 03029743

Mental health conditions significantly impact all aspects of life, highlighting the need for innovative and accessible interventions. Remote automatic dialogue systems are increasingly used in mental health interventions to help individuals express their concerns and relieve stress. We used NLP technologies to address three key challenges in mental health intervention dialogue systems: identifying user concern topics, predicting concern severity, and optimizing dialogue flow. First, we introduced a new topic clustering method to classify samples into customized categories without the need for large labeled datasets, achieving an accuracy of 73.8%. Next, we created a dataset containing user concerns and severity labels to train models for detecting severe concerns. In our evaluation, BERT achieved a Pearson correlation coefficient of 0.83 in predicting concern severity. We also used language models for dialogue flow optimization. BERT achieved an F-score of 0.752 in predicting user satisfaction. We continuously monitored and predicted user satisfaction based on conversation content, identifying flows that negatively impacted satisfaction. We believe that our AI-supported dialogue system, capable of continuous adaptation and improvement, can significantly contribute to mental health interventions.

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Real-world clinical determinants of alcohol dependence in outpatients with bipolar disorder: a multicenter treatment survey for bipolar disorder in psychiatric outpatient clinics with 2,392 participants

Tokumitsu K., Sugawara N., Adachi N., Kubota Y., Watanabe Y., Miki K., Azekawa T., Edagawa K., Katsumoto E., Hongo S., Goto E., Ueda H., Kato M., Yoshimura R., Nakagawa A., Kikuchi T., Tsuboi T., Watanabe K., Yasui-Furukori N.

Frontiers in Psychiatry 15 2024年

Background: Bipolar disorder is a psychiatric disorder characterized by mood swings between manic and depressed states that causes psychosocial problems. Cognitive function deteriorates with each recurrence, making it important to maintain remission through continued treatment. Bipolar disorder often co-occurs with alcohol dependence, which is known to lead to decreased treatment adherence and increased suicide risk. However, the real-world clinical determinants of alcohol dependence in outpatients with bipolar disorder in Japan remain unclear. Methods: We conducted an observational study targeting 2392 patients with bipolar disorder using data from the MUSUBI study, a joint project of the Japanese Association of Neuro-Psychiatric Clinics and the Japanese Society of Clinical Neuropsychopharmacology. After determining the prevalence of alcohol dependence and the sociodemographic characteristics of patients with bipolar disorder, multivariate analysis was performed to identify risk factors for alcohol comorbidity. Results: The prevalence of alcohol dependence among outpatients with bipolar disorder in this study was 5.7%. The prevalence was 7.6% for males and 3.1% for females. The results of the binomial logistic regression analysis revealed that bipolar I disorder, manic state, comorbidities with other psychiatric disorders, male sex, and suicidal ideation were significantly associated with alcohol dependence. Stratified analysis by gender showed that alcohol dependence was more strongly associated with the presence of suicidal ideation in women than in men. Limitation: First, because this was an observational study with a cross-sectional design, causal relationships between factors cannot be determined. In addition, this study included outpatients in Japan but lacked information on inpatients. Therefore, it was considered necessary to conduct the study on a larger population in order to generate more robust evidence. Conclusions: We found that outpatients with bipolar disorder, especially men, had higher rates of alcohol dependence overall than the general population in Japan. In addition, the relationship between alcohol dependence and suicidal ideation was stronger in women than in men with bipolar disorder. There was a strong association between manic states and alcohol dependence in outpatients with bipolar disorder. These results are useful to clinicians because they reinforce real-world clinical evidence for the treatment of bipolar disorder and co-occurring alcohol dependence.

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Goal Attainment Scaling for Depression: Validation of the Japanese GAS-D Tool in Patients with Major Depressive Disorder

Kato M., Kikuchi T., Watanabe K., Sumiyoshi T., Moriguchi Y., Åström D.O., Christensen M.C.

Neuropsychiatric Disease and Treatment 20 49 - 60 2024年

Purpose: Goal attainment scaling (GAS) has been proposed as a person-centric, semi-quantitative measure that assimilates achievement of individually set goals into a single standardized “goal attainment score” that can be compared at the population level. We aimed to examine the reliability and validity of the Japanese version of the GAS for depression (GAS-D) tool in assessing goal attainment in people living with major depressive disorder (MDD). Patients and Methods: This was a prespecified analysis of a prospective, 24-week, multicenter, observational cohort study of employed Japanese outpatients with MDD initiating treatment with vortioxetine according to the Japanese label (JRCT1031210200). Participants were assessed using the Japanese version of the GAS-D and other clinical rating scales at baseline and Weeks 8, 12 and 24. Results: Goal attainment was significantly associated with symptom severity as assessed by the Montgomery–Åsberg Depression Rating Scale (MADRS) scale, confirming convergent validity. In particular, GAS-D scores were significantly related to MADRS total score at Weeks 12 and 24, indicating that improvements in overall symptom severity with vortioxetine treatment were likely to be reflected in the achievement of individualized treatment goals. With an intraclass correlation coefficient of 0.67 (95% CI 0.45–0.82), the GAS-D also showed moderate test–retest reliability between Weeks 8 and 12 while proving independent of demographic characteristics. Conclusion: The results of this open-label study support the use of the GAS-D as a valid and sensitive outcome measure in the assessment of treatment response in MDD.

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Clinical characteristics and potential association to Parkinson’s disease and dementia with Lewy bodies in patients with major depressive disorder who received maintenance electroconvulsive therapy: a retrospective chart review study

Kudo S., Uchida T., Nishida H., Takamiya A., Kikuchi T., Yamagata B., Mimura M., Hirano J.

BMC Psychiatry 23 （ 1 ） 2023年12月

Background: Maintaining remission after electroconvulsive therapy (ECT) is clinically relevant in patients with depression, and maintenance ECT has been introduced in patients who fail to maintain remission after ECT. However, the clinical characteristics and biological background of patients who receive maintenance ECT are poorly understood. Thus, this study aimed to examine the clinical background of patients who underwent maintenance ECT. Methods: Patients with major depressive disorder who underwent ECT followed by maintenance ECT (mECT group) and those who did not (acute ECT [aECT] group) were included. Clinical characteristics, including the results of neuroimaging examinations for Parkinson’s disease (PD) and dementia with Levy body (DLB) such as myocardial 123I-metaiodobenzylguanidine (MIBG) scintigraphy and dopamine transporter imaging single-photon emission computerized tomography (DaT-SPECT), were compared between the groups. Results: In total, 13 and 146 patients were included in the mECT and aECT groups, respectively. Compared to the aECT group, the mECT group showed a significantly higher prevalence of melancholic features (92.3% vs. 27.4%, p < 0.001) and catatonic features (46.2% vs. 9.6%, p = 0.002). Overall, 8 of the 13 patients in the mECT group and 22 of the 146 patients in the aECT group underwent neuroimaging examinations for PD/DLB. The rate of patients examined is significantly higher in the mECT group than in the aECT group (61.5% vs. 11.2%, p < 0.001). Among the groups examined, 7/8 patients in the mECT group and 16/22 patients in the aECT group showed relevant neuroimaging findings for PD/DLB; the positive rate was not significantly different between the two groups (87.5% vs. 72.7%, p = 0.638). Conclusions: Patients who receive acute and maintenance ECT may have underlying neurodegenerative diseases, including PD/DLB. Investigating the neurobiology of patients who receive maintenance ECT is important for developing appropriate treatments for depression.

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Real-world predictors of divorce among outpatients with bipolar disorder: sex differences and clinical implications

Annals of General Psychiatry 22 （ 1 ） 2023年12月

Background: Bipolar disorder is a mental illness characterized by recurring episodes of mania and depression and is known to cause social impairment. Additionally, it has been revealed that bipolar disorder increases the risk of divorce and loss of family member support, which can worsen the prognosis. However, there is limited evidence regarding the predictive factors of divorce among patients with bipolar disorder in real-world settings. Methods: This study utilized an observational approach and involved psychiatrists from 176 member clinics of the Japanese Association of Neuro-Psychiatric Clinics. They were requested to conduct a retrospective review of medical records and complete a questionnaire focused on patients diagnosed with bipolar disorder. The data collection period for baseline patient characteristics spanned from September to October 2017. Next, we investigated the incidence of divorce over a 2-year period, ranging from baseline to September to October 2019. Results: A total of 1071 outpatients with bipolar disorder were included in the analysis, and 2.8% (30/1071) experienced divorce during the first 2 years of observation. The incidence of divorce in this population was considerably higher than that in the general Japanese population. Binomial logistic regression analysis confirmed that a younger baseline age and lower BMI values were statistically significant predictors of divorce occurrence for all study participants. The predictors of divorce were then examined separately by sex. The results revealed that for men, a younger age at baseline and having bipolar I disorder compared to bipolar II disorder were statistically significant predictors of divorce. In contrast, for women, having a lower BMI and using anxiolytics emerged as statistically significant predictors of divorce. Conclusions: In this study, a younger baseline age and lower BMI values were statistically significant predictors of divorce in patients with bipolar disorder. Notably, the predictors of divorce varied significantly between men and women. These findings provide important insights from a family perspective regarding social support for individuals with bipolar disorder in real-world clinical settings.

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Functional connectivity changes between frontopolar cortex and nucleus accumbens following cognitive behavioral therapy in major depression: A randomized clinical trial

Katayama N., Nakagawa A., Umeda S., Terasawa Y., Shinagawa K., Kikuchi T., Tabuchi H., Abe T., Mimura M.

Psychiatry Research Neuroimaging 332 2023年07月

ISSN 09254927

Cognitive behavioral therapy (CBT) is a psychotherapy that challenges distorted cognitions; however, the neural mechanisms that underpin CBT remain unclear. Hence, we aimed to assess the treatment-related resting-state functional connectivity (rsFC) changes in the brain regions associated with future thinking and the associations between rsFC changes and clinical improvements. Thirty-eight adult patients with MDD were randomly assigned with equal likelihood to receive 16-week individual CBT or talking control with a 12-month follow-up period. We evaluated the rsFC changes in the frontal regions, nucleus accumbens, amygdala, and limbic structures key to the depression pathophysiology and future thinking with 2 × 2 mixed ANOVA interaction analysis. Pearson's correlation analysis with Bonferroni's correction was also performed to examine the associations with clinical symptoms, such as depression severity and automatic thoughts in follow-up evaluations. Treatment-specific changes include enhancement in frontopolar connectivity with the nucleus accumbens. An increased rsFC was associated with lower negative automatic thoughts postoperatively, together with lower depressive symptoms and higher positive automatic thoughts at follow-up. Conclusively, rsFC changes in the fronto-limbic neural control circuit after CBT, particularly between the frontal pole and nucleus accumbens, may be clinically meaningful functional changes related to the depression recovery process.

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The effect of cognitive behavioral therapy on future thinking in patients with major depressive disorder: A randomized controlled trial

Amano M., Katayama N., Umeda S., Terasawa Y., Tabuchi H., Kikuchi T., Abe T., Mimura M., Nakagawa A.

Frontiers in Psychiatry 14 2023年01月

Background: Pessimistic thinking about the future is one of the cardinal symptoms of major depression. Few studies have assessed changes in pessimistic thinking after undergoing cognitive behavioral therapy (CBT). A randomized clinical trial (RCT) was conducted with patients diagnosed with major depressive disorder (MDD) to determine whether receiving a course of CBT affects pessimistic future thinking using a future thinking task. Methods: Thirty-one patients with MDD were randomly assigned to either CBT (n = 16) or a talking control (TC) (n = 15) for a 16-week intervention. The main outcomes were the change in response time (RT) and the ratio of the responses for positive valence, measured by the future thinking task. Secondary outcomes included the GRID-Hamilton Depression Rating Scale, the Beck Depression Inventory-Second Edition (BDI-II), the Dysfunctional Attitude Scale (DAS), and the word fluency test (WFT). Results: Regarding the main outcomes, the CBT group showed reduced RT for the positive valence (within-group Cohen’s d = 0.7, p = 0.012) and negative valence (within-group Cohen’s d = 0.6, p = 0.03) in the distant future condition. The ratio of positive valence responses in both groups for all temporal conditions except for the distant past condition increased within group (distant future: CBT: Cohen’s d = 0.5, p = 0.04; TC: Cohen’s d = 0.8, p = 0.008; near future: CBT: Cohen’s d = 1.0, p < 0.001; TC: Cohen’s d = 1.1, p = 0.001; near past: CBT: Cohen’s d = 0.8, p = 0.005; TC: Cohen’s d = 1.0, p = 0.002). As for secondary outcomes, the CBT group showed greater improvement than the TC group regarding the need for social approval as measured by the DAS (p = 0.012). Conclusion: Patients with MDD who received CBT showed a reduced RT for the positive and negative valence in the distant future condition. RT in the future thinking task for depressed patients may be a potential objective measure for the CBT treatment process. Because the present RCT is positioned as a pilot RCT, a confirmatory trial with a larger number of patients is warranted to elucidate the CBT treatment process that influences future thinking. Clinical trial registration: https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000021028, identifier UMIN000018155.

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Assessing Reliability and Validity of the Oxford Depression Questionnaire (ODQ) in a Japanese Clinical Population

Kato M., Kikuchi T., Watanabe K., Sumiyoshi T., Moriguchi Y., Åström D.O., Christensen M.C.

Neuropsychiatric Disease and Treatment 19 2401 - 2412 2023年

Purpose: Originally developed in English, the Oxford Depression Questionnaire (ODQ) is a patient-reported scale specifically developed for assessing emotional blunting in people with major depressive disorder (MDD). We aimed to examine the reliability and validity of the Japanese version of the ODQ. Patients and methods: This was a prespecified analysis of a prospective, 24-week, multicenter, observational cohort study of employed Japanese outpatients with MDD initiating treatment with vortioxetine according to the Japanese label (JRCT1031210200). Participants were assessed using the Japanese version of the ODQ and other clinical rating scales at baseline and Weeks 8, 12 and 24. Results: One hundred and sixteen patients initiated vortioxetine and had ≥1 post-baseline visit. Directionally, the associations between ODQ scores and other clinical measures were as expected and demonstrated good concurrent validity. Factor analysis shows that the scale has a good fit for three factors. The Cronbach’s α coefficient was 0.912, and the scale also showed good test–retest reliability with intraclass correlation coefficients for the ODQ total score and domains ranging between 0.69 and 0.82. ODQ scores had strong positive correlations with symptom severity assessed using the Montgomery and Åsberg Depression Rating Scale and were moderately correlated with work productivity, overall functioning, and quality of life scales. Conclusion: Data from this prospective analysis confirm that the Japanese version of the ODQ retains the good validity and reliability of the original English scale and is suitable for use in prospective studies wanting to capture treatment effects on emotional blunting in MDD.

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Predictors of psychiatric hospitalization among outpatients with bipolar disorder in the real-world clinical setting

Tokumitsu K., Yasui-Furukori N., Adachi N., Kubota Y., Watanabe Y., Miki K., Azekawa T., Edagawa K., Katsumoto E., Hongo S., Goto E., Ueda H., Kato M., Nakagawa A., Kikuchi T., Tsuboi T., Watanabe K., Shimoda K., Yoshimura R.

Frontiers in Psychiatry 14 2023年

Background: Bipolar disorder is a psychiatric disorder that causes recurrent manic and depressive episodes, leading to decreased levels of social functioning and suicide. Patients who require hospitalization due to exacerbation of bipolar disorder have been reported to subsequently have poor psychosocial functioning, and so there is a need to prevent hospitalization. On the other hand, there is a lack of evidence regarding predictors of hospitalization in real-world clinical practice. Methods: The multicenter treatment survey on bipolar disorder (MUSUBI) in Japanese psychiatric clinics was an observational study conducted to provide evidence regarding bipolar disorder in real-world clinical practice. Psychiatrists were asked, as part of a retrospective medical record survey, to fill out a questionnaire about patients with bipolar disorder who visited 176 member clinics of the Japanese Association of Neuro-Psychiatric Clinics. Our study extracted baseline patient characteristics from records dated between September and October 2016, including comorbidities, mental status, duration of treatment, Global Assessment of Functioning (GAF) score, and pharmacological treatment details. The incidence and predictors of hospitalization among patients with bipolar disorder over a 1-year period extending from that baseline to September–October 2017 were examined. Results: In total, 2,389 participants were included in our study, 3.06% of whom experienced psychiatric hospitalization over the course of 1 year from baseline. Binomial logistic regression analysis revealed that the presence of psychiatric hospitalization was correlated with bipolar I disorder, lower baseline GAF scores, unemployment, substance abuse and manic state. Conclusions: Our study revealed that 3.06% of outpatients with bipolar disorder were subjected to psychiatric hospitalization during a 1-year period that extended to September–October 2017. Our study suggested that bipolar I disorder, lower baseline GAF scores, unemployment, substance abuse and baseline mood state could be predictors of psychiatric hospitalization. These results may be useful for clinicians seeking to prevent psychiatric hospitalization for bipolar disorder.

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Development and acceptability of a decision aid for anxiety disorder considering discontinuation of benzodiazepine anxiolytic

Aoki Y., Takaesu Y., Inada K., Yamada H., Murao T., Kikuchi T., Takeshima M., Tani M., Mishima K., Otsubo T.

Frontiers in Psychiatry 14 2023年

Aim: We aimed to develop a decision aid (DA) for individuals with anxiety disorders who consider tapering benzodiazepine (BZD) anxiolytics, and if tapering, tapering BZD anxiolytics with or without cognitive behavioral therapy (CBT) for anxiety. We also assessed its acceptability among stakeholders. Methods: First, we conducted a literature review regarding anxiety disorders to determine treatment options. We cited the results of the systematic review and meta-analysis, which we conducted previously, to describe the related outcomes of two options: tapering BZD anxiolytics with CBT and tapering BZD anxiolytics without CBT. Second, we developed a DA prototype in accordance with the International Patient Decision Aid Standards. We carried out a mixed methods survey to assess the acceptability among stakeholders including those with anxiety disorders and healthcare providers. Results: Our DA provided information such as explanation of anxiety disorders, options of tapering or not tapering BZD anxiolytics (if tapering, the options of tapering BZD anxiolytics with or without CBT) for anxiety disorder, benefits and risks of each option, and a worksheet for value clarification. For patients (n = 21), the DA appeared to be acceptable language (86%), adequate information (81%), and well-balanced presentation (86%). The developed DA was also acceptable for healthcare providers (n = 10). Conclusion: We successfully created a DA for individuals with anxiety disorders who consider tapering BZD anxiolytics, which was acceptable for both patients and healthcare providers. Our DA was designed to assist patients and healthcare providers to involve decision-making about whether to taper BZD anxiolytics or not.

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Costs of psychotropics for outpatients with bipolar disorder in Japan; the MUSUBI 2016 survey

Adachi N., Kubota Y., Goto E., Watanabe K., Yoshimura R., Tsuboi T., Yasui-Furukori N., Kato M., Hongo S., Azekawa T., Katsumoto E., Edagawa K., Nakagawa A., Kikuchi T., Ueda H., Miki K.

Annals of Medicine 55 （ 1 ） 2023年

ISSN 07853890

Background: Although the costs of bipolar disorder (BD) treatments are associated with local and universal factors, data from non-Western countries remain limited. The associations between clinical features and costs of outpatient pharmacotherapy have not been well characterize. To estimate the costs of outpatient BD treatments and their associations with clinical features in a Japanese population, we investigated with special reference to the costs of medicines constituted the bulk of the total healthcare expense and were steadily increasing. Methods: The Multicenter Treatment Survey for Bipolar Disorder (MUSUBI) retrospectively evaluated 3130 patients with BD who visited 176 Japanese psychiatric outpatient clinics in 2016. Clinical features and drug prescriptions were recorded, and the total daily costs of psychotropic drug treatment were calculated. The annual medical costs related to outpatient BD treatments in Japan were estimated based on the corresponding demographics. The associations between daily medical costs and patients’ clinical features were analyzed using multiple regression analysis. Results: The daily costs of psychotropic drugs ranged from zero to JPY3245 (mean, JPY349 equivalent to USD32.5) and were exponentially distributed. The annual costs for outpatients BD treatments were approximately 51.9 billion Japanese yens (519 million US dollars). Subsequent multiple regression analysis revealed that social adjustment, depressive symptoms, age, rapid cycling, psychotic symptoms, and comorbid mental disorders correlated strongly with the daily cost of psychotropic drugs. Conclusion: The estimated annual costs for outpatient BD treatment in Japan were equivalent to those in OECD countries (except for the US) and higher than those in some Asian countries. The cost of psychotropic treatments was associated with individual characteristics and psychopathological conditions.Key Messages Psychotropic treatment for an outpatient with bipolar disorder has a daily cost approximately JPY350. The annual outpatient treatment cost for bipolar disorder in Japan was estimated to 51.9 billion Japanese yen in 2016. Individual characteristics and psychopathological conditions affected the cost of drug treatment.

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Clinical characteristics and prescriptions associated with a 2-year course of rapid cycling and euthymia in bipolar disorder: a multicenter treatment survey for bipolar disorder in psychiatric clinics

Takano C., Kato M., Adachi N., Kubota Y., Azekawa T., Ueda H., Edagawa K., Katsumoto E., Goto E., Hongo S., Miki K., Tsuboi T., Yasui-Furukori N., Nakagawa A., Kikuchi T., Watanabe K., Kinoshita T., Yoshimura R.

Frontiers in Psychiatry 14 2023年

Objective: In patients with bipolar disorder (BD), rapid cycling (RC) presents a risk for a more severe illness, while euthymia (EUT) has a better prognosis. This study focused on the progression of RC and EUT, which are contrasting phenomenology, and aimed to clarify the influence of patient backgrounds and prescription patterns on these different progressions, using a large sample from the first and second iterations of a multicenter treatment survey for BD in psychiatric clinics (MUSUBI). Methods: In the cross-sectional study (MUSUBI), a questionnaire based on a retrospective medical record survey of consecutive BD cases (N = 2,650) was distributed. The first survey was conducted in 2016, and the second one in 2017. The questionnaire collected information on patient backgrounds, current episodes, and clinical and prescribing characteristics. Results: In the first survey, 10.6% of the participants had RC and 3.6% had RC for two consecutive years, which correlated with BP I (Bipolar disorder type I), suicidal ideation, duration of illness, and the use of lithium carbonate and antipsychotic medications. Possible risk factors for switching to RC were comorbid developmental disorders and the prescription of anxiolytics and sleep medication. Moreover, 16.4% of the participants presented EUT in the first survey, and 11.0% presented EUT for two consecutive years. Possible factors for achieving EUT included older age; employment; fewer psychotic symptoms and comorbid personality disorders; fewer antidepressants, antipsychotics, and anxiolytics, and more lithium prescriptions. Conclusion: RC and EUT generally exhibit conflicting characteristics, and the conflicting social backgrounds and factors contributing to their outcomes were distinctive. Understanding these clinical characteristics may be helpful in clinical practice for management of patients with BD.

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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 13 2022年12月

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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