Published papers

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

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.

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

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

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

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

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

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

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

We have been building our UNDERPIN mental disease dialogue corpus, which includes disease types, disease severity tests, and dialogue voices with their transcriptions and audio/linguistic annotations. We trained our classifier to classify depression patients using this corpus. We defined four classes (healthy, light level, more than middle level, and recovered), then tried six pairs of binary classification of these four classes. Our classification results show that we can classify light level patients with more than middle level patients. We can also classify recovered people with healthy people. We confirmed new features that contributed to the classifications. In future, we plan to add new features, and create automatic annotation tools.

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

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