Manabu Takaki

Background: Although participation in organised extracurricular activities has been associated with higher self‐esteem, high participation frequency may have adverse effects, as proposed by the overscheduling hypothesis. Longitudinal evidence from non‐Western countries is limited. We examined whether the frequency of enrichment‐oriented out‐of‐school lessons (naraigoto) in fourth grade was associated with self‐esteem in sixth grade in a Japanese large‐scale cohort. Methods: We analysed longitudinal data from the Japanese Longitudinal Study of Children and Parents from fourth grade (baseline, 2017–2019) to sixth grade (follow‐up, 2019–2021) ( n = 3399). The exposure was the frequency of enrichment‐oriented activities in fourth grade, excluding academic tutoring (juku). The outcome was self‐confidence in sixth grade (4‐point Likert scale). Ordinal logistic regression models were employed for estimating odds ratios and 95% confidence intervals, and possible confounders (sociodemographic factors, baseline self‐confidence) were adjusted. Sensitivity analyses were also conducted using alternative outcome and alternative exposure definitions. Results: In the fully adjusted model, the adjusted odds ratios for higher self‐confidence were 1.22 (95% confidence interval 0.96–1.55) for one session/week, 1.30 (1.02–1.66) for two sessions/week, 1.34 (1.04–1.73) for three session/week, 1.41 (1.10–1.82) for four to five sessions/week, and 1.22 (0.87–1.71) for six or more sessions/week, compared with zero sessions/week (reference). Associations were strongest at two to five sessions/week, with no increase at six or more sessions/week. Results were similar in sensitivity analyses. Gender‐stratified analyses suggested that these associations were significant only in male participants. Conclusions: Enrichment activity participation was associated with self‐esteem 2 years later, with the strongest associations at moderate frequencies. Future studies should examine total amount of time and qualitative aspects of participation.

This study explored whether metaverse-based support groups could address social isolation and suicide risks among LGBTQ+ youths by providing enhanced anonymity, avatar-based self-expression, and improved accessibility. Over one year, 53 individuals aged 14–23 participated in regular online sessions facilitated via the "cluster" metaverse platform by a non-profit LGBTQ+ organization. Each 90-minute session included voice and text-based interactions within a specially designed single-floor virtual space featuring conversation areas and a designated "safe area" for emotional regulation. Post-session questionnaires (5-point Likert scales) captured demographics, avatar preferences, self-confidence, and perceived safety, self-expression, and accessibility; responses were analyzed with Pearson's chi-squared test and Mann–Whitney U tests (α=0.05). Results indicated that 79.2% of participants selected avatars aligned with their gender identity, reporting high satisfaction (mean = 4.10/5) and minimal discomfort (mean = 1.79/5). Social confidence was significantly higher in the metaverse compared with real-world settings (p

Background and Aims: The association between alcohol‐metabolizing enzyme polymorphisms and treatment response to nalmefene for alcohol dependence has not been studied. We aimed to determine whether alcohol‐metabolizing enzyme polymorphisms, specifically ADH1B rs1229984 and ALDH2 rs671, modify the treatment response to nalmefene for alcohol dependence. Design: Secondary analysis of a Japanese randomized clinical trial, in which participants were randomly assigned (4:3:4) to placebo, 10 mg nalmefene or 20 mg nalmefene groups for 24 weeks, accompanied by a brief psychosocial intervention. Setting: 80 addiction outpatient clinics across Japan. Participants: A subset of 531 individuals (mean age 49.2 years, standard deviation 11.5; 69.9% male), including 196 in the placebo group and 335 in the nalmefene group, who agreed to DNA preservation and had available DNA data between February 2015 and July 2016. Measurements: Genotyping was performed to determine ADH1B rs1229984 polymorphism (AA, AG, GG) and ALDH2 rs671 polymorphism (GG, GA, AA) in participants. Primary endpoint was change from baseline in monthly heavy drinking days (HDD, days/month) over the 24 treatment weeks. The key secondary endpoint was change from baseline in daily total alcohol consumption (TAC, g/day) over the 24 treatment weeks. Findings: A mixed‐effects model for repeated measures analyses showed a statistically significant gene‐treatment interaction with ADH1B rs1229984 for TAC [10.71 (95% confidence interval = 4.03–17.39) g/day, P = 0.002], but not for HDD [1.65 (−0.38 to 3.67) days/month, P = 0.110]: as the G allele of rs1229984 increased, the efficacy regarding TAC decreased. In contrast, no statistically significant gene‐treatment interaction was seen with ALDH2 rs671 for either TAC [4.46 (−7.88 to 16.80) g/day, P = 0.478] or HDD [−0.91 (−4.60 to 2.78) days/month, P = 0.630]. In the ADH1B rs1229984 variant, the number needed to treat for two category shifts in drinking risk level, as defined by the World Health Organization, was 3.7 for AA carriers, 6.6 for AG carriers and 18.5 for GG carriers. Conclusions: The ADH1B rs1229984 polymorphism appears to moderate the response to nalmefene in Japanese patients with alcohol dependence. Specifically, nalmefene appears to show efficacy in individuals with the ADH1B rs1229984 AA genotype.

Background: Moderate exercise increases white blood cells and neutrophils. However, there are no reports on the relationship between exercise intensity and these cells. We observed a patient taking clozapine whose white blood cell and neutrophil counts were borderline. Supervised exercise therapy with an occupational therapist stabilized these counts.Case Presentation: A 50‐year‐old woman with treatment‐resistant schizophrenia was prescribed clozapine. By Day 63, the clozapine dosage had been increased to 450 mg/day. Additionally, she was advised to perform a 30‐min walking exercise program 1 h before blood tests. Exercise therapy supervised by an occupational therapist was performed eight times, and self‐training was performed five times. Exercise intensity was monitored using the Borg Scale for subjective evaluation and the Karvonen formula for objective evaluation. Supervised exercise therapy with an occupational therapist resulted in greater increases on the Borg Scale and Karvonen formula than did self‐training. It also induced increases in white blood cells and neutrophils. Her psychiatric symptoms improved, and she was discharged on Day 71. A blood test taken after discharge revealed that her white blood cell and neutrophil counts were within the normal range and she continued to take clozapine for 2 years. She has since been able to enjoy a calm and relaxed life at home.Conclusion: Exercise involving subjective and objective evaluation by an occupational therapist effectively increased white blood cells and neutrophils during clozapine treatment. Supervised exercise therapy by an occupational therapist is important when self‐exercise is insufficient for continuing clozapine treatment.

Background: Lorlatinib is a third‐generation tyrosine kinase inhibitor for anaplastic lymphoma kinase (ALK)‐positive non‐small cell lung cancer (NSCLC). While it has a high intracranial lesion control rate, it can also cause central nervous system complications, including psychotic symptoms. We present a case of lorlatinib‐induced psychosis successfully managed with olanzapine, enabling lorlatinib rechallenge.Case Presentation: A 32‐year‐old woman with ALK‐positive NSCLC and brain metastases was started on lorlatinib. After 18 months, she developed hallucinations and delusions. Despite treatment with risperidone, her psychotic symptoms persisted, leading to hospitalization. Her symptoms resolved upon lorlatinib discontinuation while risperidone was continued. Given the critical role of lorlatinib in controlling brain metastases, rechallenge was considered. To mitigate concerns regarding drug interactions, risperidone was replaced with olanzapine. Following lorlatinib rechallenge with olanzapine, no recurrence of psychiatric symptoms was observed, allowing continued lorlatinib treatment. Additionally, no progression of lung cancer was noted.Conclusion: Lorlatinib is an essential drug for controlling brain metastases in ALK‐positive NSCLC. However, it can induce psychotic symptoms. When psychiatrists are involved in managing adverse effects during cancer treatment, close collaboration among oncologists, psychiatrists, and patients is essential.

Background: Somatic symptom disorder (SSD), which includes chronic pain, is a common mental disorder characterized by significant functional impairment and other psychiatric comorbidities. Electroconvulsive therapy (ECT) has been proposed as a potential treatment for refractory chronic pain. However, evidence supporting its efficacy is limited and/or low quality. We present a case of SSD with chronic pain in which ECT was ineffective.Case Presentation: The patient was a 63‐year‐old man with chronic pain in the lower back, buttocks, thighs, and soles of the feet. The duration of his chronic pain was 3.8 years. He was diagnosed with Bertolotti's syndrome and SSD. He did not meet the criteria for major depressive disorder. He kept physically active by walking and doing exercises to distract himself from his pain. He strongly perceived pain as a physical issue and preferred ECT over psychotherapy. Despite undergoing 10 ECT sessions with adequate seizures, his pain persisted. After four sessions, he experienced despair over the lack of improvement in pain, which temporarily intensified his suicidal ideation. After undergoing ECT, he continued to maintain his activities, including walking and exercise, while his catastrophic thinking about pain persisted.Conclusion: The ineffectiveness of ECT in this case highlights the need for balanced counseling, particularly for patients who consider ECT a last‐resort treatment. Psychological monitoring and depression screening are essential, especially given the risk of heightened despair or suicidal ideation when ECT is ineffective. Therefore, collaborative decision‐making based on accurate information is vital.

Background: Clozapine‐induced agranulocytosis (CLIA) is a rare but serious complication. Fever associated with CLIA is typically treated with broad‐spectrum antimicrobials, but empiric antifungal therapy is rarely used. While bacterial and viral infections have been reported in CLIA cases, no cases of fungal infections complicated by CLIA have been documented. We report the first case of CLIA complicated by invasive pulmonary aspergillosis (IPA) in a patient with schizophrenia. The diagnosis of IPA was made using serum β‐D‐glucan, Aspergillus galactomannan antigen tests, and chest computed tomography (CT).Case presentation: We present a case of a 51‐year‐old man with schizophrenia who developed CLIA complicated by IPA. The patient, diagnosed with treatment‐resistant schizophrenia, was started on clozapine, but 9 months later he presented with fever, cough, leukopenia, and neutropenia. Clozapine was discontinued, and empirical treatments with cefepime and filgrastim were initiated. Serum β‐D‐glucan and Aspergillus galactomannan antigen tests were positive, and chest CT showed well‐circumscribed nodules, leading to a probable diagnosis of IPA. Antifungal therapy was switched from micafungin to voriconazole according to guidelines. His neutropenia and fever improved, and he was re‐transferred to a psychiatric hospital.Conclusion: CLIA can be complicated by fungal infections. When patients with CLIA present with fever, fungal infections, including IPA, should be considered in the differential diagnosis. Serological tests, including β‐D‐glucan and Aspergillus galactomannan, are useful for the diagnosis of IPA as well as the appropriate use of antifungal agents in patients with CLIA.

Background: Inattention due to attention‐deficit/hyperactivity disorder (ADHD) can lead to forgetfulness. Transient epileptic amnesia (TEA) can cause forgetfulness, similar to ADHD. We report a patient with ADHD who developed TEA.Case Presentation: The patient was a 40‐year‐old woman with ADHD. She has been prone to forgetfulness since childhood. Two years before visiting our outpatient clinic, she had begun to occasionally forget events that had occurred several days earlier. However, she was largely unaware of the emergence of new amnestic symptoms. She had also begun to experience various other amnestic symptoms 2 months before she visited our clinic, which prompted her to visit our outpatient clinic. The combination of a detailed interview, electroencephalography (EEG) examination, and consideration of TEA enabled us to diagnose her with TEA and provide treatment accordingly. In our patient, daily forgetfulness due to ADHD delayed the recognition of new additional forgetfulness attributed to TEA.Conclusion: Psychiatrists need to consider TEA when patients with ADHD present with changes in or exacerbation of forgetfulness.