OBJECTIVE:Educational interventions can influence not only individuals who directly receive them but also nonparticipating individuals within the same cluster. This study examined whether an educational spillover effect within a cluster occurs during real-world implementation of clinical practice guidelines. METHODS:Discharge data for inpatients with schizophrenia (n = 22,032) and major depressive disorder (MDD) (n = 11,207) from 298 facilities among those participating in the Effectiveness of GUIdeline for Dissemination and Education in psychiatric treatment (EGUIDE) project between 2016 and 2024. Patients were categorized into three groups based on psychiatrist participation and facility participation: Group 1 (psychiatrist[-], facility[-]), Group 2 (psychiatrist[-], facility[+]), and Group 3 (psychiatrist[+], facility[+]). Primary outcomes were implementation rates of guideline-recommended treatments (Quality Indicators: QIs). The EGUIDE training effect was modeled as an ordinal variable (Group 1 < Group 2 < Group 3). Logistic regression adjusted for age, sex, and facility type was used to estimate Odds Ratios (ORs). RESULTS:Significant positive associations were observed for 9 of 11 QIs in schizophrenia and 5 of 7 QIs in MDD (e.g., QI-S1: assessment of treatment-resistant schizophrenia diagnosis, adjusted OR 1.98, P < 2.78 × 10-192). Guideline adherence increased sequentially from Group 1 to Group 3. CONCLUSION:This study was the first to empirically demonstrate, in a non-randomized real-world setting, that educational spillover effects extended beyond participating psychiatrists to influence nonparticipating psychiatrists within the same facility. These findings underscore the importance of leveraging facility-level spillover effects in guideline implementation strategies.

Background/Objectives: Multimodal depression detection research has traditionally relied on early or hybrid fusion strategies without systematically analyzing how dynamic fusion mechanisms interact with modality-specific pretraining. Although gated and attention-based architectures are increasingly adopted, their behavior is rarely examined within a structured fusion taxonomy framework. Methods: In this study, we conduct a controlled taxonomy-level evaluation of multimodal fusion strategies in a Japanese PHQ-9-annotated depression dataset. We compare four fusion paradigms (concatenation, summation, gated fusion, and cross-attention) across three integration stages, crossed with modality-specific affective pretraining configurations for visual (CMU-MOSI/MOSEI), acoustic (JTES), and textual (WRIME) encoders, yielding 512 experimental conditions. Results: The results reveal strong position-dependent effects of fusion strategy. Cross-attention fusion at the audio integration stage achieved the highest mean AUC (0.774) and PR-AUC (0.606), with statistically significant superiority over gated and concatenation-based fusion (Kruskal–Wallis H=86.28, p<0.001). In contrast, fusion effects at the text stage were non-significant in AUC but significant in PR-AUC, highlighting metric-sensitive behavior under class imbalance. Pretraining effects were modality-specific: SigLIP initialization produced significant positive transfer (Δ=+0.018, p<0.001), whereas audio pretraining on JTES resulted in negative transfer (Δ=−0.014, p=0.004), suggesting domain mismatch effects. Gate analysis further revealed condition-dependent modality dominance, including cases of semantic–geometric reversal under joint auxiliary augmentation. Conclusions: Our findings suggest that multimodal depression detection systems should not be interpreted through static fusion categories alone. Instead, modality contribution appears to be associated with structured interaction effects between fusion strategy, integration position, and affective pretraining. This work provides a controlled empirical bridge between fusion taxonomy and dynamic modality weighting in clinical multimodal modeling.

We previously performed data-driven classification based on large-scale neuroimaging datasets to identify a potential novel subtype of psychiatric disorders characterized by the pronounced enlarged ventricles and cognitive impairment (EVCI) in one cohort. However, these findings have yet to be validated across independent cohorts. Herein, we investigated the availability of cognitive data in other cohorts in the Cognitive Genetics Collaborative Research Organization (COCORO) project to assess the presence of cognitive impairment (CI). Subsequently, we compared the prevalence of CI, lateral ventricular volume, and demographic and clinical characteristics between individuals with EVCI and those with EV but without CI (EV-nonCI). Cognitive data were available for 27 individuals with EVCI from the other 8 cohorts. Among the 27 individuals in the EV group, 5 (18.5%) exhibited EVCI, all of whom were diagnosed with schizophrenia. Three individuals (60%) in the EVCI group were male. Compared with the EV-non-CI group, the EVCI group presented significantly lower current intellectual quotient (IQ) scores (p = 5.8 × 10-4), but there was no significant difference in premorbid IQ (p = 0.56). Furthermore, there was no significant difference in the Z scores for lateral ventricular volume between the groups (p = 0.26). This study validated the existence of the EVCI subgroup in independent cohorts, thus supporting our previous findings.

BACKGROUND:Educational interventions are widely used to promote guideline-concordant psychiatric practice. However, it remains unclear whether participants' subjective satisfaction translates into actual changes in clinical behavior (CB). This study examined the association between subjective assessment (SA) scores of the EGUIDE training programs for schizophrenia and major depressive disorder (MDD) and CB. METHODS:In this multicenter observational study, we analyzed data from psychiatrists who participated in the EGUIDE training program. SA scores were obtained immediately after training using standardized questionnaires assessing satisfaction with program content, knowledge, skills, and future clinical intentions. CB was evaluated using self-report measures of guideline-concordant practice in general, schizophrenia-specific, and MDD-specific domains. Associations between SA and CB scores were examined using Spearman's rank correlation coefficients. RESULTS:A total of 1399 psychiatrists were included in the analysis. The comprehensive SA score showed a significant positive correlation with the comprehensive CB score (r = 0.19, p < 0.001). Likewise, schizophrenia- and MDD-specific SA scores were positively correlated with all CB domains, including general guideline use and disorder-specific practices (ρ = 0.14-0.19, all p < 0.001). Although effect sizes were small, the associations were consistent across disorders and clinical domains. CONCLUSIONS:Higher satisfaction with guideline-based educational programs was associated with greater self-reported guideline-concordant CBs, suggesting that positive educational experiences may support improvements in psychiatric practice at the national level.

Aim:This study aimed to describe the nationwide reach, longitudinal growth, and geographic dissemination of the Effectiveness of Guideline for Dissemination and Education in Psychiatric Treatment (EGUIDE) project in Japan from 2016 to 2024. Methods:The EGUIDE project is a nationwide, multicenter implementation initiative designed to promote the dissemination of clinical practice guidelines, specifically the Guidelines for Pharmacological Treatment of Schizophrenia and the Treatment Guidelines II: Major Depressive Disorder. The project provides educational lectures primarily for psychiatrists and other mental health professionals. We descriptively summarized the cumulative numbers of lectures delivered, participants enrolled, and participating institutions from 2016 to 2024. In addition, we calculated the proportion of hospitals with psychiatric departments that participated in each prefecture. Results:Between 2016 and 2024, a total of 194 guideline lectures on schizophrenia and major depressive disorder were conducted. The cumulative number of participants reached 4785 across 763 institutions, of which 592 were hospitals with psychiatric departments, corresponding to approximately 20% of all such hospitals nationwide. Participating hospitals were distributed across most prefectures in Japan, indicating broad geographic coverage. Conclusion:Over the 9-year period, the EGUIDE project continuously delivered guideline lectures and steadily expanded its participant and institutional base. The nationwide distribution of participating institutions suggests that the project has established a broad implementation platform for psychiatric guideline dissemination in Japan. Continued efforts may further strengthen this dissemination network and support future evaluations of its impact on psychiatric practice.

BackgroundAdolescence is characterized by heightened self-consciousness and sensitivity to social evaluations. During this period, hostile attribution bias—interpreting ambiguous social cues as hostile—can lower quality of life (QOL) and contribute to future mental health problems. Adolescents with autism spectrum disorder (ASD) show similar difficulties, often more pronounced due to their cognitive style and interpersonal vulnerabilities. Group cognitive behavioral therapy (CBT) aims to correct such biases through structured cognitive and social experiences. This study evaluated the psychological effects of group CBT on hostile attribution bias, social functioning, and QOL in adolescents and young adults with ASD traits.MethodsWe conducted an 8-session group CBT program focusing on hostile attribution bias and suspiciousness in 21 adolescents and young adults with ASD traits attending a hospital psychiatric outpatient department. The 15 participants who completed the program were included in analyzes. Psychological indices included hostile attribution bias (Ambiguous Intentions Hostility Questionnaire), social functioning (Social Responsiveness Scale, Second Edition [SRS-2]), and subjective QOL. Pre–post changes were quantified as change rates ((post − pre)/pre × 100). Group-level changes were tested with paired analyzes; exploratory associations among change rates were examined using Spearman correlations.ResultsGroup CBT significantly improved hostile attribution bias (effect size [ES] = 0.698, p = 0.017), social communication and interaction (SRS-2; ES = 0.780, p = 0.012), and subjective QOL (ES = 0.752, p = 0.011). Exploratory individual-level analyzes showed a discordant pattern: smaller reductions in hostile attribution bias (less negative change rates) were associated with greater increases in subjective QOL (ρ = 0.597, p = 0.019).ConclusionsThis pilot study suggests that group CBT may reduce hostile attribution bias and improve QOL and social functioning in adolescents and young adults with ASD traits. Notably, the positive correlation between hostile attribution bias change rates and QOL change rates suggests that greater QOL gains were not necessarily accompanied by larger reductions in hostile attribution bias, indicating that improvements in cognitive bias and perceived well-being may arise through partly distinct or non-linear pathways rather than a simple one-to-one relationship.Clinical trial registryUniversity Hospital Medical Information Network (UMIN000030140).

ABSTRACT Aim Clinical practice guidelines have improved the quality and standardization of psychiatric care; however, their long‐term implementation in real‐world settings remains limited. The Effectiveness of the Guidelines for Dissemination and Education (EGUIDE) project was established to promote sustained evidence‐based practice through a multilayered educational program for psychiatrists in Japan. Methods This multicenter observational study longitudinally tracked psychiatrists' self‐rated clinical behavior (CB) scores related to guideline adherence for up to 8 years after initial EGUIDE participation. CB was assessed using a validated questionnaire covering general guideline use (CB‐G), schizophrenia (CB‐S), and major depressive disorder (CB‐D), with a comprehensive index (CB‐C) representing the mean of all domains. Data were analyzed using the Kruskal–Wallis test, the Mann–Whitney U test, and the Bonferroni correction (two‐tailed p < 0.05). Results A total of 1562 psychiatrists (mean age, 32.7 ± 7.1 years) were included. All CB indices (CB‐C, CB‐G, CB‐S, and CB‐D) significantly improved post training compared with the baseline (H = 831.2–984.0; all p < 10−72), with small‐to‐moderate effect sizes (r = 0.09–0.29). These improvements were maintained throughout the 8‐year follow‐up, with no significant decline, and several domains showed small but continued increases between 3 and 7 years post training. Conclusion The EGUIDE program achieved long‐term, sustained improvements in psychiatrists' guideline‐adherent clinical behaviors through an integrated system combining education, supervision, feedback, and follow‐up. This autonomous, cyclical framework represents a high‐impact model for continuous quality improvement and may be adaptable to other medical specialties.

Aims:Previous studies have identified alterations in one-carbon metabolism (OCM), including DNA methylation abnormalities, in individuals with schizophrenia. However, the precise etiology of this disorder remains unclear. In the present study, we examined variations in the expression of DNMT1 and DNMT3a-genes implicated in DNA methylation-using peripheral blood leukocytes from Japanese patients with chronic schizophrenia and healthy controls. Additionally, using our previously acquired data, we explored the association between OCM-related factors and DNMT expression levels. Methods:Expression levels of DNMT1 and DNMT3a in 215 patients with chronic schizophrenia and 210 healthy controls were quantified using real-time PCR. The Mann-Whitney U test was used to compare the differences between two independent groups. Furthermore, Spearman's correlation analysis was conducted to investigate the relationships between DNMT genes` expression levels and OCM-related metabolites (blood folate, vitamin B6, and total homocysteine). Results:The expression levels of DNMT1 and DNMT3a in peripheral leukocytes were significantly elevated in patients with chronic schizophrenia compared with controls (p = 1.4 × 10-6 and 2.9 × 10-3, respectively). DNMT1 mRNA expression levels exhibited a weak negative correlation with folate exclusively in the aggregated cohort (N = 425) (ρ = -0.16, adjusted q = 5.0 × 10-3), and DNMT3a mRNA expression levels showed a weak negative correlation with vitamin B6 alone in the combined group (ρ = -0.12, adjusted q = 0.03). Conclusion:These findings suggest a potential correlation between nutritional status and elevated expression of DNMT1 and DNMT3a in schizophrenia. Our findings contribute to the understanding of the epigenetic mechanisms associated with schizophrenia and highlight the need for further investigation of the relationships among gene expression, nutritional status, and psychiatric manifestations.

To evaluate changes in amyloid burden on serial amyloid PET before and after donanemab treatment in a real-world clinical cohort. This retrospective study included 20 consecutive patients who underwent serial amyloid PET before and after donanemab treatment. Quantitative analysis was performed using Centiloid values and tracer-specific standardized uptake value ratios (SUVr). Visual assessment was also performed to determine amyloid-positive or amyloid-negative status before and after treatment. Centiloid values significantly decreased from 52.3 ± 23.4 at baseline to − 5.6 ± 16.5 at follow-up, with a mean change of − 58.0 (p < 0.001). All patients showed a reduction in Centiloid values. In the flutemetamol group (n = 12), pons-referenced SUVr significantly decreased, while in the florbetapir group (n = 8), cerebellar-referenced SUVr also showed significant reductions (both p < 0.001). On visual assessment, 17 of 20 patients (85

OBJECTIVE:The Effectiveness Research on the Dissemination and Education of Psychiatric Clinical Practice Guidelines (EGUIDE Project) was launched in Japan to promote guideline-adherent treatment for schizophrenia and major depressive disorder (MDD) through educational outreach programs. Although short-term effects on participating physicians have been reported, the long-term and facility-wide effects remain unclear. This study evaluated whether guideline-compliant treatment behaviors improved across institutions over time, indicating potential diffusion or spillover effects. METHODS:We conducted a prospective observational study involving 298 psychiatric facilities between 2016 and 2023. Discharge prescriptions and treatment data were collected for 19 623 patients with schizophrenia and 9805 patients with MDD. Adherence to the guidelines was assessed using 11 schizophrenia quality indicators (QI-S) and seven MDD quality indicators (QI-D). We performed logistic regression analyses, adjusting for age, sex, and facility type, with Bonferroni correction for multiple comparisons. RESULTS:For schizophrenia, significant year-on-year improvements were observed in seven of the 11 QI-S, including assessment of treatment-resistant schizophrenia (TRS) diagnosis (from 42.2% to 62.5%), use of modified electroconvulsive therapy (mECT; from 6.1% to 11.8%), and nonprescription of anticholinergics (from 70.7% to 81.7%). For MDD, three of the seven QI-D showed improvement, including assessment of severity diagnosis (from 51.2% to 77.0%) and use of mECT (from 12.8% to 26.6%). Notably, the implementation of cognitive behavioral therapy (CBT) decreased. These findings suggest long-term behavioral changes across all facilities, extending even to nonparticipating clinicians. CONCLUSION:The presence of EGUIDE-trained psychiatrists was associated with sustained improvements in guideline-compliant treatments at the institutional level. These results imply not only individual educational benefits but also a diffusion of practice culture-that is, a spillover effect-leading to enhanced quality of psychiatric care. Continued educational efforts are essential to improving treatment practices at scale. TRIAL REGISTRATION:The protocol for the EGUIDE Project is registered with the University Hospital Medical Information Network Registry (UMIN000022645).

Importance:Despite the rising prevalence of bulimia nervosa and the associated risks of chronicity and severe physical and psychological morbidity, access to effective treatment remains poor. The effectiveness and acceptability of internet-based cognitive behavior therapy (ICBT) for women with bulimia nervosa in clinical settings in East Asia remain unclear. Objective:To determine the effectiveness and acceptability of a guided ICBT program to treat women with bulimia nervosa in Japan. Design, Setting, and Participants:This randomized clinical trial was conducted at 7 university hospitals in Japan between August 2022 and October 2024. This study enrolled female participants aged 13 to 65 years whose symptoms met the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) criteria for bulimia nervosa, had a body mass index (BMI) of 17.5 or greater, had internet access, and had no history of practicing CBT-related techniques within the past 2 years. Interventions:Both the control and intervention groups received usual care. The intervention consisted of ICBT with additional guidance from a therapist. The therapy program was tailored to Japanese culture and grounded in a specific cognitive behavior model, and it was performed over a 12-week period. Main Outcomes and Measures:Severity of bulimia nervosa, measured by the weekly combined frequency of episodes involving binge eating and compensatory behaviors, was assessed by a blinded, independent rating team at baseline and at the 12-week intervention end point. Intention-to-treat analyses were conducted using a linear mixed model with effect sizes calculated using Cohen d. Results:A total of 61 women met the eligibility criteria and were randomized to the intervention group (n = 31) or the control group (n = 30). Participants were predominantly young (mean [SD] age, 27.8 [9.0] years), had normal weight (mean [SD] BMI, 21.1 [3.6]), and had a mean (SD) duration of illness of 9.3 (8.8) years; half (31 [50.8%]) were employed. Intent-to-treat analysis revealed that guided ICBT significantly reduced the weekly combined frequency of episodes involving binge eating and compensatory behaviors (by an adjusted mean difference of 9.84 episodes [95% CI, 2.49-17.18 episodes], P = .01; Cohen d = 0.73 [95% CI, 0.21-1.26]). Sensitivity analyses supported these findings. Conclusions and Relevance:In this randomized clinical trial, the intervention group experienced a significant decrease in bulimia symptoms compared with the control group, supporting the effectiveness and acceptability of the therapist-guided ICBT program. These findings suggest that integration of therapist-guided ICBT in usual care has the potential to improve accessibility to efficacious treatment options for women with bulimia nervosa. Trial Registration:UMIN Clinical Trials Registry Identifier: UMIN00048732.

Abstract Background The creation of a novel diagnostic system using objective biomarkers is expected to take place, due to difficulty of the current diagnostic system based on symptoms in psychiatry. Aims & Objectives We clustered the 5602 subjects based on brain subcortical volumes and showed a four-biotype classification, namely extremely (Brain Biotype [BB] 1: n=110) and moderately smaller limbic regions (BB2: n=566), larger basal ganglia (BB3: n=679), and normal volumes (BB4: n=4247), being associated with cognitive/social functioning (Mol Psychiatry, 2023). In the present study, we performed a detailed examination of the biological and clinical characteristics of these biotypes. Method A total of 5602 patients in the previous paper, including healthy subjects (n=3077), patients with schizophrenia (SZ: n=1499), bipolar disorder (BD: n=234), major depressive disorder (MDD: n=598), autism spectrum disorder (ASD: n=189) and other psychiatric disorders (O: n=5), were included. The biological and clinical characteristics of four biotypes were investigated using subcortical volumes from T1-weighted MRI images, cognitive functions, EEG, and genomic information. Results We examined the differences in subcortical volume characteristics in each biotype and found that the lateral ventricle volume was remarkably larger (Z-score = 5.1 ± 1.8) in BB1 (n=110). 99.1% of BBI subjects had the lateral ventricle volume greater than 3 standard deviation (3 SD) of normal subjects, and this brain feature discriminated BB1 with a sensitivity of 99.1% and a specificity of 98.1%. Therefore, BB1 was redefined as a brain structural feature with a lateral ventricular volume of 3 SD or greater. Of the 186 redefined subjects, 33 patients with detailed cognitive function data were stratified into two groups: 9 patients with moderate or higher cognitive decline (SZ8/ASD1) and 24 patients with mild or lower cognitive decline (SZ9/ HC9/ASD4/ MDD1/O1), and compared. EEG abnormalities (71% in the former group, 0% in the latter), a diagnosis of schizophrenia (89% in the former group, 38% in the latter group), and low intelligence (IQ=67 in the former group, IQ=103 in the latter group) were obviously observed in the former group than in the latter. Furthermore, copy number variation analysis of 7 out of 9 cases in the former group showed a high rate of pathological CNV (22q11.21 deletion, 7q11.23 duplication, and DPP6 deletion) in 3 cases, which is only seen in approximately one out of several thousand normal subjects. Discussion & Conclusion We have identified a novel candidate for classification of psychiatric disorders with high rates of EEG abnormalities, psychotic symptoms, and pathological rare genomic variants in a stratified group of patients with schizophrenia and other psychiatric disorders with lateral ventricular volumes of 3 SD or greater and moderate to severe cognitive decline. We proposed a possible novel psychiatric disorder by going back to each patient based on the clinical significance from a large-scale data-driven analysis screening, and proposed a methodology to find the concept and psychiatric disorders by objective indices for the first time in the world.This new biotype classification suggests that objective measurements based on neuroimaging data will be incorporated into psychiatric diagnosis in the future.

AIM:The concomitant use of lamotrigine and valproic acid, a uridine diphosphate (UDP)-glucuronosyltransferase inhibitor, is a known risk factor for lamotrigine-induced rashes, which may develop into fatal or severe cutaneous adverse reactions. No drugs other than valproic acid have been shown to increase lamotrigine concentrations in humans by inhibiting UDP-glucuronosyltransferase. The treatment of bipolar disorder and epilepsy is often combined with other medications, which may affect the risk of rash. We aimed to identify medications that increased the risk of lamotrigine-induced rashes using clinical data. METHODS:We used VigiBase to search for drugs associated with the increased number of reported severe cutaneous adverse reactions when combined with lamotrigine. In a retrospective study, we collected information on patients from electronic medical records and used propensity score matching to compare the incidence of lamotrigine-induced rash with and without flunitrazepam use. Furthermore, we compared lamotrigine concentrations between patients treated with and without flunitrazepam in a prospective observational study. RESULTS:VigiBase analysis showed that flunitrazepam significantly increased the reporting odds ratio for lamotrigine-related severe cutaneous adverse reactions. In the retrospective study, combining lamotrigine with flunitrazepam significantly increased the incidence of rashes. In the prospective observational study, lamotrigine with flunitrazepam significantly increased the concentration-to-dose ratio. CONCLUSION:Flunitrazepam use may affect lamotrigine concentration and increase the risk of rash. These results have implications for the choice of sleep medication. In addition, when lamotrigine is used in combination with flunitrazepam, the lamotrigine dosing design should address lamotrigine-induced rash management.

Quantitative analysis of amyloid positron emission tomography (PET) is increasingly applied in clinical and research settings; however, its consistency across software platforms remains uncertain. This study aimed to compare standardized uptake value ratio (SUVr) measurements obtained from CortexID Suite and VIZCalc, to evaluate their concordance with expert visual assessment, and to assess the concordance of Centiloid values derived from VIZCalc with the visual reference. We retrospectively analyzed 116 patients who underwent 18F-flutemetamol PET at a single institution. SUVr values were calculated using both CortexID Suite and VIZCalc, while Centiloid values were derived from VIZCalc only. Visual assessments were performed by two nuclear medicine physicians. Correlations among indices were examined using Pearson’s correlation. Agreement between SUVr values was assessed with Bland–Altman analysis. Agreement with the non-independent visual reference was evaluated using receiver operating characteristic (ROC) analysis, and areas under the curves (AUCs) were compared with DeLong’s test. SUVr values from CortexID and VIZCalc were strongly correlated (r = 0.986, p < 0.001), with a small mean difference of + 0.0397. Both platforms showed high concordance with the non-blinded visual assessment (AUC: 0.991 for CortexID; 0.989 for VIZCalc). Centiloid values also showed high agreement with the visual reference (AUC: 0.994) and were strongly correlated with SUVr values (r = 0.975 for CortexID; r = 0.965 for VIZCalc, p < 0.001). No significant difference was observed between platforms (p = 0.84). CortexID Suite and VIZCalc demonstrated high concordance with the non-blinded visual assessment and showed consistent quantitative trends. Both platforms can be reliably applied for amyloid burden quantification, provided that software-specific characteristics are appropriately considered.

ABSTRACT One of the challenges in diagnosing psychiatric disorders is that the results of biological and neuroscience research are not reflected in the diagnostic criteria. Thus, data‐driven analyses incorporating biological and cross‐disease perspectives, regardless of the diagnostic category, have recently been proposed. A data‐driven clustering study based on subcortical volumes in 5604 subjects classified into four brain biotypes associated with cognitive/social functioning. Among the four brain biotypes identified in controls and patients with schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder, and other psychiatric disorders, we further analyzed the brain biotype 1 subjects, those with an extremely small limbic region, for clinical utility. We found that the representative feature of brain biotype 1 is enlarged lateral ventricles. An enlarged ventricle, defined by an average z‐score of left and right lateral ventricle volumes > 3, had a sensitivity of 99.1% and a specificity of 98.1% for discriminating brain biotype 1. However, the presence of an enlarged ventricle was not sufficient to classify patient subgroups, as 1% of the controls also had enlarged ventricles. Reclassification of patients with enlarged ventricles according to cognitive impairment resulted in a stratified subgroup that included patients with a high proportion of schizophrenia diagnoses, electroencephalography abnormalities, and rare pathological genetic copy number variations. Data‐driven clustering analysis of neuroimaging data revealed subgroups with enlarged ventricles and cognitive impairment. This subgroup could be a new diagnostic candidate for psychiatric disorders. This concept and strategy may be useful for identifying biologically defined psychiatric disorders in the future.

Abstract Background In Japan, the Effectiveness of Guidelines for Dissemination and Education (EGUIDE) psychiatric treatment project was launched in 2016. In the EGUIDE project, we developed a 2-day education course for psychiatrists to learn Japanese treatment guidelines for schizophrenia and major depressive disorder (MDD) (one day for each disorder). In this program, we also evaluated the participants’ prescribing activity (prescription at admission and discharge for patients with schizophrenia or MDD) to assess the effectiveness of our program. Our previous report showed that polypharmacy of the main treatment drug (antipsychotics in schizophrenia and antidepressants in major depressive disorder) and additional prescription of psychotropics other than the main drug were common in Japan. In the current study, by assessing changes in prescriptions during hospitalization, we aimed to identify the clues that improve pharmacological prescriptions for patients with schizophrenia. Methods Psychiatrists were recruited between April 2016 and September 2020. Written informed consent was obtained from all the participants after the procedures had been fully explained by a chief researcher at the facility. This study was approved by the ethics committees of the National Center of Neurology and Psychiatry (A2017-105) and each participating university, hospital, or clinic. The study was conducted in accordance with the Declaration of Helsinki. The study protocol was registered in the University Hospital Medical Information Network Registry (UMIN000022645).Data on prescriptions at admission and discharge from 2016 to 2020 were collected. We divided the patients into four groups: 1) mono_mono group, monotherapy of the main drug at admission and discharge; 2) mono_poly group, monotherapy at admission and polypharmacy at discharge; 3) poly_poly group, polypharmacy at admission and discharge; and 4) poly_mono group, polypharmacy at admission and monotherapy at discharge. We compared the changes in dosage and number of psychotropics among the four groups. Results For patients with schizophrenia, the patients who received monotherapy with the main drug at admission were likely to receive main drug monotherapy at discharge and vice versa. When monotherapy of main drug at admission became polypharmacy at discharge, the number of concomitant psychotropic medications also increased. On the other hand, when polypharmacy of main drug at admission became monotherapy at discharge, the number of concomitant psychotropic medications also decreased. Conclusions Our results showed that patients who received monotherapy with the main drug at admission were more likely to receive monotherapy at discharge and vice versa. In addition, when the main treatment involved a polypharmacy regimen, the number of psychotropic drugs prescribed besides the main treatment drug tended to increase. These results suggest that it is critical to avoid a polypharmacy regimen as the main treatment for schizophrenia. We gathered follow-up data from the same psychiatrists and assessed the changes in prescription patterns after these psychiatrists received special instructions regarding the guidelines. We expect clinicians to prescribe higher rates of monotherapy with the main drug after receiving special instructions regarding the guidelines.

Background:Bipolar disorder (BD) is a psychiatric disorder characterized by recurrent episodes of mania and depression. However, the pathophysiology has not yet been fully elucidated. Methods:In this study, we employed capillary electrophoresis time-of-flight mass spectrometry to measure 34 plasma metabolites and compared the levels between individuals with BD (N = 64, male/female = 30/34, age [mean ± S.D.] = 51.4 ± 12.0 years) and non-psychiatric controls (N = 92, male/female = 32/60, age = 38.6 ± 13.4 years). Results:Significant differences in 12 plasma metabolites, including kynurenine and tryptophan, were observed between the two groups (q < 0.05). Discussion:These findings support the involvement of amino acid dysregulation in the pathophysiology of BD. However, the cross-sectional design, lack of control for medication, diet, and smoking, and the use of peripheral rather than central samples limit the generalizability of the results. Further longitudinal and mechanistic studies are needed. Integration with clinical, imaging, and genetic data in future research may facilitate the development of metabolomics-based biomarkers.

Aim:The Effectiveness of Guideline for Dissemination and Education in Psychiatric Treatment (EGUIDE) project has improved psychiatrists' adherence to guidelines and their treatment behavior for hospitalized patients. However, treatment behavior toward outpatients has not been sufficiently investigated. This study aimed to examine the effects of the EGUIDE program on the clinical behavior of psychiatrists toward outpatients with major depressive disorder (MDD). Methods:A comparative study was conducted among outpatients at seven facilities. The study included 255 patients who had received a primary diagnosis of MDD at the initial visit and had been followed for 6 months or more since the initial visit. The prescription types were investigated at the 6-month follow-up. The primary outcomes were the rate of severity diagnosis, the rate of antidepressant monotherapy without other psychotropics, the rate of antidepressant monotherapy, the rate of no anxiolytic/hypnotic prescriptions, and the rate of intermittent psychotropic medication prescription. The secondary outcomes were the imipramine equivalent dose of antidepressants and the diazepam equivalent dose of anxiolytics/hypnotics. Results:Patients treated by psychiatrists who were participating in the EGUIDE project had a significantly higher rate of severity diagnosis than patients treated by psychiatrists who were not participating in the EGUIDE project. However, there were no significant differences in the other primary outcomes. In terms of the secondary outcomes, the diazepam equivalent dose was significantly lower in patients treated by psychiatrists who were participating in the EGUIDE project. Conclusion:Participation in the EGUIDE project was associated with improved severity diagnosis rates among outpatients with MDD, but its effect on prescribing behaviors was limited.

BACKGROUND AND HYPOTHESIS:The rate of antipsychotic polypharmacy is high. One risk factor for antipsychotic polypharmacy may be the severity of schizophrenia, including treatment-resistant schizophrenia (TRS). We hypothesized that the institutions that are able to prescribe clozapine present differences in pharmacological treatment even before TRS is diagnosed. STUDY DESIGN:A total of 8155 patients with schizophrenia were divided into the clozapine-available institution (CAI) group and the clozapine-unavailable institution (CUI) group. The psychotropic prescription rates at discharge were compared between the two groups. Furthermore, to investigate whether the diagnosis of TRS subgroups influenced treatment efficacy, we compared CAIs and CUIs with descriptions of subgroups with TRS (DSTRS) and those without descriptions of subgroups with TRS (NDSTRS). RESULTS:Compared to the CUI group, the rates of both antipsychotic monotherapy (58.3% vs. 50.7%; P = 2.4 × 10-7) and antipsychotic monotherapy without the concomitant use of other psychotropics (20.4% vs. 15.6%; P = 3.8 × 10-5) were significantly higher in the CAI group. The rate of antipsychotic monotherapy in the CAI with DSTRS group (63.3%) was significantly higher than that in the CAI with NDSTRS group (54.5%; P = 1.4 × 10-12), the CUI with DSTRS group (49.6%; P = 4.9 × 10-9), and the CUI with NDSTRS group (50.9%; P = 2.0 × 10-8). The rate of antipsychotic monotherapy without the concomitant use of other psychotropics in the CAI with DSTRS group (22.6%) was also significantly higher than that in the CAI with NDSTRS group (18.7%; P = 4.7 × 10-4), the CUI with DSTRS group (15.9%; P = 5.5 × 10-4), and the CUI with NDSTRS group (15.2%; P = 8.0 × 10-5). There was no significant difference in these rates between the other groups. CONCLUSIONS:Both the availability of clozapine prescriptions and the precise diagnosis of TRS subgroups at discharge can promote the development of an organizational culture that facilitates the treatment of patients with schizophrenia.

Background Antipsychotics are used in treatment of schizophrenia. Although antipsychotic monotherapy is recommended in most guidelines, the prescription rate of antipsychotic polypharmacy is still high, and the rates of antipsychotics and other concomitant psychotropics are different among each institution. Although the detailed causes for these differences are not well known, one of the reasons of psychotropics polypharmacy, including antipsychotics polypharmacy, may be associated with severity of schizophrenia including treatment resistant schizophrenia (TRS). With regard to TRS, institutions with a low TRS examination rate was associated with a low clozapine prescription rate. Thus, the differences of institutions, which is available to clozapine prescriptions or not, may be affected the treatment characteristics of overall schizophrenia in each institution. Aims & Objectives We examined the characteristics of psychotropic prescriptions, including antipsychotics, at the time of discharge depending on whether the institutions were available to clozapine prescriptions or not. Methods We assessed 8155 schizophrenia patients nationwide from 207 institutions from 2017 to 2020 in Japan. We divided patients into clozapine-available institutions (CAI) group and clozapine-unavailable institutions (CUI) group. We analyzed and compared the psychotropic prescription data at discharge between two groups. We defined “antipsychotic monotherapy” as the prescription of a single antipsychotic regardless of concomitant use of other psychotropics, and we defined “complete antipsychotic monotherapy” as the prescription of a single antipsychotic without concomitant use of other psychotropics. Furthermore, to investigate that the diagnosis of subgroups about TRS or not may influence the treatment, we analyzed the description of subgroups about TRS (DSTRS) or no description of subgroups about TRS (NDSTRS), and we divided the patients into four groups such as CAI with DSTRS, CAI with NDSTRS, CUI with DSTRS, and CUI with NDSTRS, and compared between four groups using the same method. We defined p <1.9 × 10-3 (0.05/27) as significant by post hoc analyses for multiple comparisons of categories. Results The number of patients was 6793 in the CAI group and 1362 in the CUI group. The rate of antipsychotic monotherapy in the CAI group was significantly higher than that in the CUI group (58.3% vs 50.7%), and the rate of complete antipsychotic monotherapy in the CAI group was significantly higher than that in the CUI group (20.4% vs 15.6%). The rate of DSTRS was significantly lower in the CAI group than the CUI group (43.6% vs 49.4%). The rate of antipsychotic monotherapy (56.0%) and complete antipsychotic monotherapy (20.0%) in the CAI group except patients prescribed clozapine were also significantly higher than that in the CUI group. The rate of antipsychotic monotherapy in the CAI with DSTRS group (63.3%) and the rate of complete antipsychotic monotherapy in the CAI with DSTRS group (22.6%) were significantly higher than that in the other three groups. Discussion & Conclusion Both establishment of clozapine prescription and the precise diagnosis of subgroups about TRS or not at discharge in each institution would lead clinicians to the treatment which may contribute to the higher psychotropic monotherapy rate for overall schizophrenia treatment.