Elsevier BVActa Medica Okayama1353-80201432026Biallelic CAG repeat expansion in the ATXN2 gene presenting with parkinsonism and spasticity108168ENYosukeOsakadaDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityChikaMatsuokaDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYumikoNakanoDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukiTairaDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTaijunYunokiDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYusukeFukuiDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityRyutaMoriharaDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMamiTakemotoDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukoKawaharaDepartment of Neurology, Okayama Saiseikai General HospitalYumikoKutokuDepartment of Neurology, Kawasaki Medical SchoolManabuTakakiDepartment of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesOsamuYokotaDepartment of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesToruYamashitaDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroyukiIshiuraDepartment of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0964-26337032025Prevalence and Modifiable Risk Factors of Dementia in People With Down Syndrome: Cross‐Sectional Study of Japan in Collaboration With the Intellectual Diversity for Goodness Research Consortium (INDIGO‐2019)329336ENShintaroTakenoshitaDepartment of Neuropsychiatry, Okayama University HospitalSeishiTeradaDepartment of Neuropsychiatry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomokazuInoueAsahigawaso Research Institute, Social Welfare Corporation AsahigawasoTakuKurozumiAsahigawaso Research Institute, Social Welfare Corporation AsahigawasoManabuTakakiDepartment of Neuropsychiatry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityRyozoKuwanoAsahigawaso Research Institute, Social Welfare Corporation AsahigawasoShigeruSuemitsuAsahigawaso Research Institute, Social Welfare Corporation AsahigawasoBackground: People with Down syndrome (DS) have a strong genetic predisposition to Alzheimer's disease (AD). However, the clinical burden and associated risk factors in diverse, non-Western populations remain less understood. This study aimed to investigate the prevalence of dementia in Japanese adults with DS and to identify modifiable clinical factors associated with dementia.<br>
Methods: This cross-sectional multicentre study surveyed 133 adults with DS (mean age 50.1 years) residing in 45 welfare facilities across Japan in 2019. Dementia was diagnosed by a consensus panel of physicians using established criteria (DSM-5, ICD-10, DC-LD) after comprehensive assessments, including the Japanese version of the Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID-J). Logistic regression analysis was performed to identify factors independently associated with dementia.<br>
Results: Forty-six participants (34.6%) were diagnosed with dementia. The prevalence rose sharply with age: 0% in their 30s, 30.8% in their 40s, 31.6% in their 50s and 65.5% in their 60s. After adjusting for covariates, older age, female sex, dyslipidaemia and visual impairment were independently associated with dementia.<br>
Conclusions: This study, the largest of its kind in Asia, confirms a high prevalence of dementia in institutionalized Japanese adults with DS. Crucially, this study is the first to identify dyslipidaemia and visual impairment as independent and potentially modifiable risk factors in this population. These findings highlight tangible targets for clinical interventions aimed at mitigating dementia risk in people with DS.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama0276-34782025DSOK-0011 Potentially Regulates Circadian Misalignment and Affects Gut Microbiota Composition in Activity-Based Anorexia ModelENHirokiKawaiDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNanamiWadaDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiSakamotoDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenjiMiyazakiSumitomo Pharma Co. LtdTaroKatoSumitomo Pharma Co. LtdYoshihiroHoriuchiSumitomo Pharma Co. LtdHiroshiKiriiDepartment of Animal Applied Microbiology, Okayama University Graduate School of Environmental, Life, Natural Science and TechnologyHoang DuyNguyenDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKenjiHinotsuDepartment of Neuropsychiatry, Okayama University HospitalYoshioOhyaDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakahiroAsadaDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAkiyoshiYokodeDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukoOkahisaDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHarukoMiyazakiDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshitakaOohashiDepartment of Molecular Biology and Biochemistry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesManabuTakakiDepartment of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesObjective: 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 11β-hydroxysteroid dehydrogenase type 1 (11β-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 11β-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 11β-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.Springer Science and Business Media LLCActa Medica Okayama1432-053314912025Cerebral Braak stage and amygdala granular fuzzy astrocyte status have independent effects on neuronal 3R-tau and 4R-tau accumulations in the olfactory bulb, respectively, in cases with low to intermediate AD neuropathologic change36ENOsamuYokotaDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomokoMikiDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHanaeNakashima-YasudaOkayama University Medical SchoolHidekiIshizuOkayama University Medical SchoolTakashiHaraguchiDepartment of Neurology, National Hospital Organization Minami-Okayama Medical CenterAkinoriMiyashitaDepartment of Molecular Genetics, Brain Research Institute, Niigata UniversityTakeshiIkeuchiDepartment of Molecular Genetics, Brain Research Institute, Niigata UniversityMasatoHasegawaDementia Research Project, Tokyo Metropolitan Institute of Medical ScienceNaotoNishikawaDepartment of Neuropsychiatry, Okayama University HospitalShintaroTakenoshitaDepartment of Neuropsychiatry, Okayama University HospitalSeishiTeradaDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesManabuTakakiDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNo potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2769-2558432025Occupational therapist‐guided exercise increased white blood cell and neutrophil counts during clozapine treatment: A case reporte70167ENKenjiHinotsuDepartment of Neuropsychiatry, Okayama University HospitalShinjiSakamotoDepartment of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHirokiKawaiDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoshioOhyaDepartment of Neuropsychiatry, Okayama University HospitalAkiyoshiYokodeDepartment of Neuropsychiatry, Okayama University HospitalTakahiroAsadaDepartment of Neuropsychiatry, Okayama University HospitalYukoOkahisaDepartment of Neuropsychiatry, Okayama University HospitalManabuTakakiDepartment of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesBackground: 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 DernegiActa Medica Okayama2792-0232522025Metaverse Support Groups for LGBTQ+ Youth: An Observational Study on Safety, Self-Expression, and Early Intervention156167ENJoeHaseiOkayama UniversityYosukeMatsumotoDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHirokiKawaiDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukoOkahisaDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesManabuTakakiDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToshifumiOzakiScience of Functional Recovery and Reconstruction, Graduate School of Medicine, Dentistry and Pharmaceu-tical Sciences, Okayama UniversityThis 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<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’s 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.Springer Science and Business Media LLCActa Medica Okayama1432-053315012025Biallelic variants in DNAJC7 cause familial amyotrophic lateral sclerosis with the TDP-43 pathology19ENToruYamashitaDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOsamuYokotaDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDaikiOusakaDepartment of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHongmingSunDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakashiHaraguchiDepartment of Neurology, National Hospital Organisation Minami-Okayama Medical CentreRicardo SatoshiOta-ElliottDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesChikaMatsuokaDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomohitoKawanoDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHanaeNakashima-YasudaDepartment of Psychiatry, Zikei HospitalYusukeFukuiDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYumikoNakanoDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyutaMoriharaDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasatoHasegawaDepartment of Brain and Neurosciences, Tokyo Metropolitan Institute of Medical ScienceYasuyukiHosonoDepartment of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeishiTeradaDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesManabuTakakiDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroyukiIshiuraDepartment of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of motor neurons. ALS pathology primarily involves the failure of protein quality control mechanisms, leading to the accumulation of misfolded proteins, particularly TAR DNA-binding protein 43 (TDP-43). TDP-43 aggregation is a central pathological feature of ALS. Maintaining protein homeostasis is critical and facilitated by heat shock proteins (HSPs), particularly the HSP40 family, which includes co-chaperones such as DNAJC7. Here, we report a family with three siblings affected by ALS who carry a homozygous c.518dupC frameshift variant in DNAJC7, a member of the HSP40 family. All three patients exhibited progressive muscle weakness, limb atrophy, bulbar palsy, and respiratory failure. Pathological examination revealed degeneration of both upper and lower motor neurons, with phosphorylated TDP-43-positive neuronal cytoplasmic inclusions in the frontal and temporal cortices. Immunoblot analysis were consistent with a type B pattern of phosphorylated TDP-43 in the precentral gyrus. Immunohistochemistry and RNA sequencing analyses demonstrated a substantial reduction in DNAJC7 expression at both the protein and RNA levels in affected brain regions. In a TDP-43 cell model, DNAJC7 knockdown impaired the disassembly of TDP-43 following arsenite-induced stress, whereas DNAJC7 overexpression suppressed the assembly and promoted the disassembly of arsenite-induced TDP-43 condensates. Furthermore, in a zebrafish ALS model, dnajc7 knockdown resulted in increased TDP-43 aggregation in motor neurons and reduced survival. To the best of our knowledge, this study provides the first evidence linking biallelic loss-of-function variants in DNAJC7 to familial ALS with TDP-43 pathology.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0168-01022182025Alteration of perineuronal nets and parvalbumin interneurons in prefrontal cortex and hippocampus, and correlation with blood corticosterone in activity-based anorexia model mice104922ENHoang DuyNguyenDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHarukoMiyazakiDepartment of Molecular Biology and Biochemistry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesHirokiKawaiDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesZiyiWangDepartment of Molecular Biology and Biochemistry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesShinjiSakamotoDepartment of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesManabuTakakiDepartment of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesToshitakaOohashiDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAnorexia nervosa (AN) is an eating disorder characterized by restricted energy intake, severely underweight status, and frequent hyperactivity. Previous research has shown structural and functional alterations in the medial prefrontal cortex (mPFC) and hippocampus of AN patients. To investigate the pathological mechanism of AN, we analyzed the expression and distribution of parvalbumin (PV) interneurons and perineuronal nets (PNNs), which are implicated in the pathology of neuropsychiatric disorders, in the mPFC and hippocampus dorsal (HPCd) and ventral (HPCv) using an activity-based anorexia (ABA) mouse model. We found that PNN expression and density increased in the mPFC, with minor alterations in the HPCd and HPCv of ABA mice. The expression and distribution of PV neurons were unchanged in the brains of ABA mice, except for a regional decrease in PV-expressing neuron density in the HPCd. Co-localization analysis showed an increased number of PNNs enwrapping PV-negative neurons in the mPFC of ABA mice. Furthermore, the upregulation of PNN expression in the mPFC was positively correlated with elevated blood corticosterone levels, a well-known stress indicator, in ABA mice. Our findings suggest that the increased expression and distribution of PNNs surrounding PV-negative neurons in the mPFC may indicate the pathological mechanisms of AN.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2769-2558422025Olanzapine enabled rechallenge after lorlatinib-induced psychosis: A case reporte70091ENAkiyoshiYokodeDepartment of Neuropsychiatry, Okayama University HospitalMasakiFujiwaraDepartment of Neuropsychiatry, Okayama University HospitalYukoNakamuraDepartment of Neuropsychiatry, Okayama University HospitalKadoakiOhashiDepartment of Respiratory Medicine, Okayama University HospitalShinjiSakamotoDepartment of Neuropsychiatry, Okayama University HospitalManabuTakakiDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine,Dentistry, and Pharmaceutical SciencesBackground: 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.<br>
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.<br>
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.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2769-2558422025A case report of ineffective electroconvulsive therapy for chronic paine70108ENTakashiFukaoDepartment of Neuropsychiatry, Okayama University HospitalMasakiFujiwaraDepartment of Neuropsychiatry, Okayama University HospitalYutoYamadaDepartment of Neuropsychiatry, Okayama University HospitalKazushiAsadaDepartment of Neuropsychiatry, Okayama University HospitalTakahiroAsadaDepartment of Neuropsychiatry, Okayama University HospitalHirotoshiRiDepartment of Neuropsychiatry, Okayama University HospitalShinjiSakamotoDepartment of Neuropsychiatry, Okayama University HospitalManabuTakakiDepartment of Neuropsychiatry, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesBackground: 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.<br>
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.<br>
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.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2769-2558412025A case of invasive pulmonary aspergillosis associated with clozapine-induced agranulocytosise70077ENAkiyoshiYokodeDepartment of Neuropsychiatry, Okayama University HospitalMasakiFujiwaraDepartment of Neuropsychiatry, Okayama University HospitalToshikiTeraoDepartment of Hematology and Oncology, Okayama University HospitalShinjiSakamotoDepartment of Neuropsychiatry, Okayama University HospitalYutoYamadaDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesRyotaSatoOkayama Psychiatric Medical CenterMomokoMishimaOkayama Psychiatric Medical CenterYujiYadaOkayama Psychiatric Medical CenterKen-IchiMatsuokaDepartment of Hematology, Endocrinology and Metabolism, Tokushima University Graduate School of Biomedical SciencesManabuTakakiDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical SciencesBackground: 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 beta-D-glucan, Aspergillus galactomannan antigen tests, and chest computed tomography (CT). <br>
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 beta-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. <br>
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 beta-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.No potential conflict of interest relevant to this article was reported.BMJ Publishing GroupActa Medica Okayama2755-97342712024Potential dopaminergic deficit in patients with geriatric psychiatric disorders as revealed by DAT-SPECT: a cross-sectional study19ENShintaroTakenoshitaDepartment of Neuropsychiatry, Okayama University HospitalSeishiTeradaDepartment of Neuropsychiatry, Okayama University Faculty of Medicine Dentistry and Pharmaceutical SciencesKatsuhideKojimaDepartment of Radiology, Okayama University HospitalNaotoNishikawaDepartment of Neuropsychiatry, Okayama University HospitalTomokoMikiDepartment of Neuropsychiatry, Okayama University HospitalOsamuYokotaDepartment of Neuropsychiatry, Okayama University Faculty of Medicine Dentistry and Pharmaceutical SciencesMasakiFujiwaraDepartment of Neuropsychiatry, Okayama University HospitalManabuTakakiDepartment of Neuropsychiatry, Okayama University Faculty of Medicine Dentistry and Pharmaceutical SciencesBackground It has been reported that patients with geriatric psychiatric disorders include many cases of the prodromal stages of neurodegenerative diseases. Abnormal I-123-2 beta-carbomethoxy-3 beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane dopamine transporter single-photon emission computed tomography (DAT-SPECT) reveals a nigrostriatal dopaminergic deficit and is considered useful to detect dementia with Lewy bodies and Parkinson's disease as well as progressive supranuclear palsy and corticobasal degeneration. We aimed to determine the proportion of cases that are abnormal on DAT-SPECT in patients with geriatric psychiatric disorders and to identify their clinical profile. <br>
Methods The design is a cross-sectional study. Clinical findings of 61 inpatients aged 60 years or older who underwent DAT-SPECT and had been diagnosed with psychiatric disorders, but not neurodegenerative disease or dementia were analysed. <br>
Results 36 of 61 (59%) had abnormal results on DAT-SPECT. 54 of 61 patients who had DAT-SPECT (89%) had undergone I-123-metaiodobenzylguanidine myocardial scintigraphy (I-123-MIBG scintigraphy); 12 of the 54 patients (22.2%) had abnormal findings on I-123-MIBG scintigraphy. There were no cases that were normal on DAT-SPECT and abnormal on I-123-MIBG scintigraphy. DAT-SPECT abnormalities were more frequent in patients with late-onset (55 years and older) psychiatric disorders (69.0%) and depressive disorder (75.7%), especially late-onset depressive disorder (79.3%). <br>
Conclusion Patients with geriatric psychiatric disorders include many cases showing abnormalities on DAT-SPECT. It is suggested that these cases are at high risk of developing neurodegenerative diseases characterised by a dopaminergic deficit. It is possible that patients with geriatric psychiatric disorders with abnormal findings on DAT-SPECT tend to show abnormalities on DAT-SPECT first rather than on I-123-MIBG scintigraphy.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2769-2558332024Forgetfulness in adult attention-deficit/hyperactivity disorder masks transient epileptic amnesia: a case reporte70003ENTakashiFukaoDepartment of Neuropsychiatry, OkayamaUniversity HospitalMasakiFujiwaraDepartment of Neuropsychiatry, OkayamaUniversity HospitalYutoYamadaDepartment of Neuropsychiatry, OkayamaUniversity HospitalShinjiSakamotoDepartment of Neuropsychiatry, OkayamaUniversity HospitalYosukeMatsumotoOkayama University Hospital Gender CenterManabuTakakiDepartment of Neuropsychiatry, OkayamaUniversity Faculty of Medicine, Dentistry andPharmaceutical SciencesBackground: 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.<br>
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.<br>
Conclusion: Psychiatrists need to consider TEA when patients with ADHD present with changes in or exacerbation of forgetfulness. We report a patient with ADHD who developed TEA. In our patient, daily forgetfulness due to ADHD delayed the recognition of new additional forgetfulness attributed to TEA. Psychiatrists need to consider TEA when patients with ADHD present with changes or exacerbation of forgetfulness. No potential conflict of interest relevant to this article was reported.BMCActa Medica Okayama2051-59601212024Pure argyrophilic grain disease revisited: independent effects on limbic, neocortical, and striato-pallido-nigral degeneration and the development of dementia in a series with a low to moderate Braak stage121ENOsamuYokotaDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomokoMikiDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHanaeNakashima-YasudaOkayama University Medical School HidekiIshizuOkayama University Medical School TakashiHaraguchiDepartment of Neurology, National Hospital Organization Minami Okayama Medical CenterChikakoIkedaOkayama University Medical School MasatoHasegawaDementia Research Project, Tokyo Metropolitan Institute of Medical ScienceAkinoriMiyashitaDepartment of Molecular Genetics, Brain Research Institute, Niigata UniversityTakeshiIkeuchiDepartment of Molecular Genetics, Brain Research Institute, Niigata UniversityNaotoNishikawaDepartment of Neuropsychiatry, Okayama University HospitalShintaroTakenoshitaDepartment of Neuropsychiatry, Okayama University HospitalKoichiroSudoDepartment of Psychiatry, Tosa HospitalSeishiTeradaDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesManabuTakakiDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAgyrophilic grains (AGs) are age-related limbic-predominant lesions in which four-repeat tau is selectively accumulated. Because previous methodologically heterogeneous studies have demonstrated inconsistent findings on the relationship between AGs and dementia, whether AGs affect cognitive function remains unclear. To address this question, we first comprehensively evaluated the distribution and quantity of Gallyas-positive AGs and the severity of neuronal loss in the limbic, neocortical, and subcortical regions in 30 cases of pure argyrophilic grain disease (pAGD) in Braak stages I-IV and without other degenerative diseases, and 34 control cases that had only neurofibrillary tangles with Braak stages I-IV and no or minimal A beta deposits. Then, we examined whether AGs have independent effects on neuronal loss and dementia by employing multivariate ordered logistic regression and binomial logistic regression. Of 30 pAGD cases, three were classified in diffuse form pAGD, which had evident neuronal loss not only in the limbic region but also in the neocortex and subcortical nuclei. In all 30 pAGD cases, neuronal loss developed first in the amygdala, followed by temporo-frontal cortex, hippocampal CA1, substantia nigra, and finally, the striatum and globus pallidus with the progression of Saito AG stage. In multivariate analyses of 30 pAGD and 34 control cases, the Saito AG stage affected neuronal loss in the amygdala, hippocampal CA1, temporo-frontal cortex, striatum, globus pallidus, and substantia nigra independent of the age, Braak stage, and limbic-predominant age-related TDP-43 encephalopathy (LATE-NC) stage. In multivariate analyses of 23 pAGD and 28 control cases that lacked two or more lacunae and/or one or more large infarctions, 100 or more AGs per x 400 visual field in the amygdala (OR 10.02, 95% CI 1.12-89.43) and hippocampal CA1 (OR 12.22, 95% CI 1.70-87.81), and the presence of AGs in the inferior temporal cortex (OR 8.18, 95% CI 1.03-65.13) affected dementia independent of age, moderate Braak stages (III-IV), and LATE-NC. Given these findings, the high density of limbic AGs and the increase of AGs in the inferior temporal gyrus may contribute to the occurrence of dementia through neuronal loss, at least in cases in a low to moderate Braak stage.No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155813522023統合失調症の歩み― 精神分裂病から自己免疫性精神病へ―6371ENManabuTakakiDepartment of Neuropsychiatry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNo potential conflict of interest relevant to this article was reported.Oxford Univ PressActa Medica Okayama1461-14572452020Mechanisms Underlying the Comorbidity of Schizophrenia and Type 2 Diabetes Mellitus367382ENYutakaMizukiDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShinjiSakamotoDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukoOkahisaDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYujiYadaDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNozomuHashimotoDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesManabuTakakiDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNorihitoYamadaDepartment of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesThe 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.Acta Medica Okayama2962014Human Rho guanine nucleotide exchange factor 11 gene is associated with schizophrenia in a Japanese population552558ENYutakaMizukiManabuTakakiYukoOkahisaShinjiSakamotoMasafumiKodamaHiroshiUjikeYosukeUchitomiObjectiveThe 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.BioMed CentralActa Medica Okayama32003No association between the sigma receptor type 1 gene and schizophrenia: results of analysis and meta-analysis of case-control studiesENNaohikoUchidaHiroshiUjikeKenjiNakataManabuTakakiAkiraNomuraTakeshiKatsuYujiTanakaTakakiImamuraAyumuSakaiShigetoshiKuroda<p><b>Background:</b> Several lines of evidence have supported possible roles of the sigma receptors in the etiology of schizophrenia and mechanisms of antipsychotic efficacy. An association study provided genetic evidence that the sigma receptor type 1 gene (SIGMAR1) was a possible susceptibility factor for schizophrenia, however, it was not replicated by a subsequent study. It is necessary to evaluate further the possibility that the SIGMAR1 gene is associated with susceptibility to schizophrenia.
Methods: A case-control association study between two polymorphisms of the SIGMAR1 gene, G-241T/C-240T and Gln2Pro, and schizophrenia in Japanese population, and meta-analysis including present and previous studies.<br />
<b>Results:</b>There was no significant association of any allele or genotype of the polymorphisms with schizophrenia. Neither significant association was observed with hebephrenic or paranoid subtype of schizophrenia. Furthermore, a meta-analysis including the present and previous studies comprising 779 controls and 636 schizophrenics also revealed no significant association between the SIGMAR1 gene and schizophrenia.<br />
<b>Conclusion:</b> In view of this evidence, it is likely that the SIGMAR1 gene does not confersusceptibility to schizophrenia.</p>No potential conflict of interest relevant to this article was reported.Acta Medica Okayama2002Two Kinds of mitogen-activated protein kinase phosphatases, MKP-1 and MKP-3, are differentially activated by acute and chronic methamphetamine treatment in the rat brainENNo potential conflict of interest relevant to this article was reported.