Wiley Acta Medica Okayama 0276-3478 2025 DSOK-0011 Potentially Regulates Circadian Misalignment and Affects Gut Microbiota Composition in Activity-Based Anorexia Model EN Hiroki Kawai Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nanami Wada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Sakamoto Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Miyazaki Sumitomo Pharma Co. Ltd Taro Kato Sumitomo Pharma Co. Ltd Yoshihiro Horiuchi Sumitomo Pharma Co. Ltd Hiroshi Kirii Department of Animal Applied Microbiology, Okayama University Graduate School of Environmental, Life, Natural Science and Technology Hoang Duy Nguyen Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenji Hinotsu Department of Neuropsychiatry, Okayama University Hospital Yoshio Ohya Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahiro Asada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akiyoshi Yokode Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuko Okahisa Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Haruko Miyazaki Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshitaka Oohashi Department of Molecular Biology and Biochemistry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Manabu Takaki Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Objective: Anorexia nervosa (AN) is a metabolic-psychiatric disorder characterized by severe weight loss, hypercortisolemia, and hypothalamic–pituitary–adrenal (HPA) axis activation. In this study, we investigated the effect of inhibiting cortisol regeneration via the enzyme 11��-hydroxysteroid dehydrogenase type 1 (11��-HSD1) on the pathophysiology of AN.<br> Method: Female C57BL/6J mice underwent a 7-day activity-based anorexia (ABA) paradigm, involving 3 h daily feeding and free access to wheels, until 25% body weight loss or experiment completion. Mice were orally treated once daily with a potent 11��-HSD1 inhibitor, DSOK-0011, or vehicle. Body weight, food intake, and activity transitions were recorded; plasma corticosterone and cholesterol levels were measured using a fluorometric assay; gut microbiota were analyzed using 16S rRNA sequencing; and hippocampal glial cells were analyzed using immunohistochemistry.<br> Results: DSOK-0011-treated mice exhibited a modest but significant increase in postprandial wheel-running activity compared to baseline (4–5 p.m., p = 0.018; 5–6 p.m., p = 0.043), whereas vehicle-treated mice showed higher preprandial activity (9–10 a.m., p = 0.0229). Gut microbiota analysis revealed increased alpha diversity in ABA mice, with a specific enrichment of the Lachnospiraceae family in the DSOK-0011 group. However, DSOK-0011 did not significantly affect body weight, food intake, corticosterone, and lipid levels, or hippocampal glial cell populations.<br> Conclusion: Inhibition of 11��-HSD1 by DSOK-0011 was associated with microbiota alterations and subtle shifts in activity timing under energy-deficient conditions. These findings suggest that peripheral glucocorticoid metabolism may influence microbial and behavioral responses in the ABA model, although its metabolic impact appears limited in the acute phase. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2769-2558 4 3 2025 Occupational therapist�]guided exercise increased white blood cell and neutrophil counts during clozapine treatment: A case report e70167 EN Kenji Hinotsu Department of Neuropsychiatry, Okayama University Hospital Shinji Sakamoto Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hiroki Kawai Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshio Ohya Department of Neuropsychiatry, Okayama University Hospital Akiyoshi Yokode Department of Neuropsychiatry, Okayama University Hospital Takahiro Asada Department of Neuropsychiatry, Okayama University Hospital Yuko Okahisa Department of Neuropsychiatry, Okayama University Hospital Manabu Takaki Department of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences 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.<Br> 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.<br> 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. No potential conflict of interest relevant to this article was reported.

Izmir Akademi Dernegi Acta Medica Okayama 2792-0232 5 2 2025 Metaverse Support Groups for LGBTQ+ Youth: An Observational Study on Safety, Self-Expression, and Early Intervention 156 167 EN Joe Hasei Okayama University Yosuke Matsumoto Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroki Kawai Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuko Okahisa Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Manabu Takaki Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshifumi Ozaki Science of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceu-tical Sciences, Okayama University 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 (��=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<0.001), particularly among those with lower real-world confidence, who exhibited an average gain of 2.08 points. Approximately half of all first-time participants were aged 16 years or younger, which suggested the platform�fs value for early intervention. Additionally, the metaverse environment was rated significantly higher in safety/privacy (3.94/5), self-expression (4.02/5), and accessibility (4.21/5) compared with the real-world baseline, and 73.6% reported they felt more accepted virtually. However, some participants who had high confidence offline experienced mild adaptation challenges (mean decrease of 0.58 points), which highlighted that metaverse-based support may be more effective as a complement to in-person services rather than a replacement. Overall, these findings demonstrate that metaverse-based support groups can reduce psychological barriers for LGBTQ+ youth by facilitating safe and affirming virtual environments. The metaverse may help alleviate emotional distress and prevent further severe outcomes, such as suicidal ideation by providing early intervention, especially for adolescents unable to access conventional in-person services. Further research should examine its integration with existing clinical, community, and educational resources to ensure comprehensive, long-term support. No potential conflict of interest relevant to this article was reported.

Oxford Univ Press Acta Medica Okayama 1461-1457 24 5 2020 Mechanisms Underlying the Comorbidity of Schizophrenia and Type 2 Diabetes Mellitus 367 382 EN Yutaka Mizuki Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Sakamoto Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuko Okahisa Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuji Yada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nozomu Hashimoto Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Manabu Takaki Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Norihito Yamada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The mortality rate of patients with schizophrenia is high, and life expectancy is shorter by 10 to 20 years. Metabolic abnormalities including type 2 diabetes mellitus (T2DM) are among the main reasons. The prevalence of T2DM in patients with schizophrenia may be epidemiologically frequent because antipsychotics induce weight gain as a side effect and the cognitive dysfunction of patients with schizophrenia relates to a disordered lifestyle, poor diet, and low socioeconomic status. Apart from these common risk factors and risk factors unique to schizophrenia, accumulating evidence suggests the existence of common susceptibility genes between schizophrenia and T2DM. Functional proteins translated from common genetic susceptibility genes are known to regulate neuronal development in the brain and insulin in the pancreas through several common cascades. In this review, we discuss common susceptibility genes, functional cascades, and the relationship between schizophrenia and T2DM. Many genetic and epidemiological studies have reliably associated the comorbidity of schizophrenia and T2DM, and it is probably safe to think that common cascades and mechanisms suspected from common genes' functions are related to the onset of both schizophrenia and T2DM. On the other hand, even when genetic analyses are performed on a relatively large number of comorbid patients, the results are sometimes inconsistent, and susceptibility genes may carry only a low or moderate risk. We anticipate future directions in this field. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0165-1781 216 2 2014 Four polymorphisms of the pericentriolar material 1 (PCM1) gene are not associated with schizophrenia in a Japanese population 288 289 EN Shinji Sakamoto Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Manabu Takaki Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuko Okahisa Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yutaka Mizuki Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masafumi Kodama Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Ujike Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Uchitomi Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 29 6 2014 Human Rho guanine nucleotide exchange factor 11 gene is associated with schizophrenia in a Japanese population 552 558 EN Yutaka Mizuki Manabu Takaki Yuko Okahisa Shinji Sakamoto Masafumi Kodama Hiroshi Ujike Yosuke Uchitomi ObjectiveThe human Rho guanine nucleotide exchange factor 11 (ARHGEF11) gene is one of the candidate genes for type 2 diabetes mellitus (T2DM). ARHGEF11 is mapped to chromosome 1q21, which has susceptible risk loci for T2DM and schizophrenia. We hypothesized that ARHGEF11 contributes to the pathogenesis of schizophrenia. MethodWe selected eight single nucleotide polymorphisms of ARHGEF11 that had significant associations with T2DM for a case-control association study of 490 patients with schizophrenia and 500 age-matched and sex-matched controls. ResultsWe did not find any differences in allelic, genotypic associations, or minor allele frequencies with schizophrenia. Analysis of the rs6427340-rs6427339 haplotype and the rs822585-rs6427340-rs6427339 haplotype combination provided significant evidence of an association with schizophrenia (global permutations p=0.00047 and 0.0032, respectively). C-C of the rs6427340-rs6427339 haplotype and A-C-C of the rs822585-rs6427340-rs6427339 haplotype carried higher risk factors for schizophrenia (permutation p=0.0010 and 0.0018, respectively). A-C-T of the rs822585-rs6427340-rs6427339 haplotype had a possible protective effect (permutation p=0.031). ConclusionThese results provide new evidence that ARHGEF11 may constitute a risk factor for schizophrenia. No potential conflict of interest relevant to this article was reported.