Psychiatry and Clinical Neurosciences最新文献

{"title":"Mosaic variants of neurodevelopmental and mitochondrial genes in postmortem paraventricular thalamus in bipolar disorder detected by deep exome sequencing.","authors":"Masaki Nishioka, Zen-Ichi Tanei, Yuko Saito, Maho Morishima, Mizuki Hino, Kanako Mori, Atsuko Nagaoka, Risa Shishido, Rie Saito, Hideaki Kitamura, Akito Nagakura, Araki Kimura, Shuji Iritani, Kenichi Oshima, Akiyoshi Kakita, Yasuto Kunii, Shigeo Murayama, Tadafumi Kato","doi":"10.1111/pcn.13871","DOIUrl":"https://doi.org/10.1111/pcn.13871","url":null,"abstract":"<p><strong>Aim: </strong>The genetic architecture of bipolar disorder (BD) remains incompletely understood despite extensive genomic studies. Postzygotic mosaic variants have emerged as promising contributors to BD; however, the landscape of such variants in the BD brain has yet to be elucidated.</p><p><strong>Methods: </strong>We analyzed mosaic variants in the paraventricular thalamic region (PVR) from 18 Japanese BD cases and 11 controls using deep whole-exome sequencing. Candidate variants were validated via targeted amplicon sequencing. To explore their biological implications, we performed gene ontology analysis by integrating the brain-derived mosaic variants identified in this study with mosaic variants previously detected in peripheral tissues.</p><p><strong>Results: </strong>We identified 99 exonic and 13 mitochondrial heteroplasmic variants in the PVR. There was a significant enrichment of deleterious mosaic variants in constrained genes (P = 0.0402) and of non-synonymous mosaic variants in neurodevelopmental genes, particularly those involved in the positive regulation of neuron projection development (false discovery rate = 2.32 × 10^-3). These genes also formed a significantly enriched protein-protein interaction network (P = 0.0106). Notably, we detected one mitochondrial variant known to be pathogenic for mitochondrial disease and two predicted pathogenic mitochondrial tRNA variants in BD cases, but none in controls.</p><p><strong>Conclusion: </strong>Despite the modest sample size and potential confounding factors such as age and cancer status, our direct analysis of brain tissue supports previous findings of an enrichment of mosaic variants in neurodevelopmental and mitochondrial tRNA genes. These results advance our understanding of the genetic underpinnings of BD.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autoantibodies and Inflammation in Schizophrenia.","authors":"Hiroki Shiwaku","doi":"10.1111/pcn.13872","DOIUrl":"https://doi.org/10.1111/pcn.13872","url":null,"abstract":"<p><p>The potential role of autoantibodies in the etiology of schizophrenia is a key research focus because growing evidence suggests an association between immune dysfunction and psychotic disorders. This hypothesis is supported by findings indicating immune-related abnormalities in patients with schizophrenia, including chronic inflammation and genetic alterations associated with immune system dysregulation. Epidemiological studies have reinforced this perspective by demonstrating a significant correlation between autoimmune diseases and schizophrenia, suggesting shared pathological mechanisms including autoantibodies. A particularly compelling line of evidence comes from the identification of autoantibodies targeting synaptic molecules in patients with schizophrenia. Autoantibodies against N-methyl-D-aspartate (NMDA) receptors, gamma-aminobutyric acid (GABA) receptors, neural cell adhesion molecule 1 (NCAM1), and neurexin 1 (NRXN1) have been detected in patients, raising the possibility that immune-mediated synaptic dysfunction contributes to the disorder's pathophysiology. Experimental studies support this notion because the administration of these autoantibodies in mice induces molecular, cellular, and behavioral abnormalities that mirror aspects of schizophrenia. This review summarizes the relationships among schizophrenia, inflammation, immune-related genetic factors, autoimmune diseases, and autoantibodies. Furthermore, this review discusses future research directions for further elucidating the role of autoantibodies in schizophrenia.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mental health consequences of visibility: How seeing others' situations influences well-being.","authors":"Akihiro Nishi, Michael Mengual","doi":"10.1111/pcn.13873","DOIUrl":"https://doi.org/10.1111/pcn.13873","url":null,"abstract":"","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flunitrazepam increases the risk of lamotrigine-induced cutaneous adverse reactions: Combined analysis of medical big data and clinical research.","authors":"Hiroshi Bando, Mitsuhiro Goda, Masahito Nakataki, Keita Hirai, Yuki Nitta, Kei Kawada, Toshihiko Yoshioka, Masaya Kanda, Atsushi Ogawa, Chiaki Mukuta-Murakami, Kaito Tsujinaka, Koji Miyata, Kohei Kitagawa, Takahiro Niimura, Fuka Aizawa, Kenta Yagi, Yuki Izawa-Ishizawa, Masayuki Chuma, Takafumi Naito, Yoshikazu Tasaki, Shusuke Numata, Keisuke Ishizawa","doi":"10.1111/pcn.13866","DOIUrl":"https://doi.org/10.1111/pcn.13866","url":null,"abstract":"<p><strong>Aim: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute and long-term effects of repeated ketamine infusions in treatment-resistant depression and associated metabolite changes.","authors":"Hitoshi Sakurai, Daiki Setoyama, Takahiro A Kato, Hisateru Tachimori, Masami Murao, Yasuyuki Matsumoto, Teruo Tada, Yayoi Imamura, Hiroyuki Seki, Takashi Tsuboi, Hiroyuki Uchida, Koichiro Watanabe","doi":"10.1111/pcn.13870","DOIUrl":"https://doi.org/10.1111/pcn.13870","url":null,"abstract":"<p><strong>Aim: </strong>This study aims to investigate the acute and sustained antidepressant effects of repeated ketamine infusions in patients with treatment-resistant depression (TRD), and to identify early metabolomic changes predictive of treatment outcomes using metabolome analyses.</p><p><strong>Methods: </strong>This open-label study investigated the effects of four intravenous ketamine infusions (0.5 mg/kg) administered over 2 weeks in 30 patients with TRD. Clinical outcomes, including the Montgomery-Åsberg Depression Rating Scale (MADRS), were evaluated at baseline, 1-2 h after each infusion, and monthly during a 12-month follow-up. Plasma levels of 11 depression-associated metabolites were measured at baseline and 1.5-2 h after the first infusion. A general linear model was employed to analyze the association between metabolite changes after the first infusion and the MADRS score percent improvements after the fourth infusion and at 12 months. Remission was defined as a MADRS score of ≤10.</p><p><strong>Results: </strong>All participants completed the four infusions. The MADRS score decreased from 30.6 ± 6.1 at baseline to 20.3 ± 11.5 after the fourth infusion, with a remission rate of 26.7%. At 12 months, 13.3% of participants remained in remission. Changes in 3-hydroxybutyrate levels after the first infusion predicted the MADRS score percent improvements after the fourth infusion (β = 1.35, 95% CI: 0.41-2.30, P = 0.005) and at 12 months (β = 1.38, 95% CI: 0.37-2.39, P = 0.007).</p><p><strong>Conclusion: </strong>While repeated ketamine infusions demonstrated rapid antidepressant effects, sustained remission was achieved in a minority of patients with TRD. 3-Hydroxybutyrate may serve as a biomarker for predicting treatment response. These findings underscore the potential for individualized strategies using ketamine infusions.</p><p><strong>Clinical trial registration: </strong>jRCTs031210648 (Japan Registry of Clinical Trials).</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma circulating microRNAs and symptoms of depression: Results from a population-based study.","authors":"Midas M Kuilman, Tim Finke, M Arfan Ikram, Annemarie I Luik, Alexander Neumann, Charlotte A M Cecil, Mohsen Ghanbari","doi":"10.1111/pcn.13869","DOIUrl":"https://doi.org/10.1111/pcn.13869","url":null,"abstract":"<p><strong>Background: </strong>Depression is a complex mental disorder with a multifactorial etiology. Recent research has highlighted the potential of microRNAs (miRNAs) as novel biomarkers and their involvement in the molecular pathways underlying depression; yet, these studies often focus on limited clinical samples and specific subsets of miRNAs. Here we aimed to explore plasma miRNA expression profiles associated with depressive symptoms in a population-based study of middle-aged and older adults.</p><p><strong>Methods: </strong>We analyzed the levels of 591 circulating miRNAs well-expressed in plasma samples of 2,703 participants of the Rotterdam Study. The Center for Epidemiologic Studies Depression Scale was used to assess depressive symptoms in these participants. Negative-binomial regression models were employed to explore the relationship between individual miRNA levels and depressive symptoms, adjusting for potential confounders including age, sex, BMI, and other factors.</p><p><strong>Results: </strong>Our analysis suggests 38 circulating miRNAs to be potentially associated with depressive symptoms (P < 0.05). Although these miRNAs did not survive multiple testing correction, our subsequent in silico analysis of their target genes suggests involvement in neural and psychiatric pathways, as well as enrichment for associations with depressive symptoms based on previous genome-wide association studies.</p><p><strong>Conclusions: </strong>This study proposes several circulating miRNAs that may be associated with depressive symptoms within the general population. Our follow-up analyses indicate that the miRNAs with the largest effect estimates were potentially involved in neurological and psychiatric processes, warranting further investigation into their potential role in the biological mechanisms of depression. These results provide preliminary insights and should be considered exploratory and hypothesis-generating, warranting validation in future studies with larger and independent cohorts.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Norman Sartorius: A true legend in psychiatry, renowned for inspiring and mentoring early-career psychiatrists across the globe.","authors":"Masaru Tateno, Takahiro A Kato, Hidehiko Takahashi","doi":"10.1111/pcn.13868","DOIUrl":"https://doi.org/10.1111/pcn.13868","url":null,"abstract":"","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnosing schizophrenia spectrum disorders: Large language models (LLMs) vs. leading international psychiatrists (LIPs).","authors":"Andrea Raballo, Federico Ravenda, Antonietta Mira","doi":"10.1111/pcn.13864","DOIUrl":"https://doi.org/10.1111/pcn.13864","url":null,"abstract":"","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive subtypes in youth at clinical high risk for psychosis.","authors":"Walid Yassin, James B Green, Matcheri Keshavan, Elisabetta C Del Re, Jean Addington, Carrie E Bearden, Kristin S Cadenhead, Tyrone D Cannon, Barbara A Cornblatt, Daniel H Mathalon, Diana O Perkins, Elaine F Walker, Scott W Woods, William S Stone","doi":"10.1111/pcn.13861","DOIUrl":"10.1111/pcn.13861","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to identify and characterize cognitive subtypes among youth at clinical high risk (CHR) for psychosis.</p><p><strong>Methods: </strong>We conducted a cluster analysis on cognitive measures in a large sample of CHR patients (CHR; n = 764) and healthy controls (HCs; n = 280) from NAPLS-2 (North American Prodrome Longitudinal Study 2). These findings were independently validated using a comparably large sample from NAPLS-3 (n = 628 CHR, 84 HCs). Statistical approaches were employed to compare cognitive, clinical, and functional trajectories at baseline and during 24 months of follow-up, with further analysis of conversion status within these clusters.</p><p><strong>Results: </strong>Two cognitive clusters, \"impaired\" and \"intact,\" were identified in the CHR group. Baseline differences in verbal abilities and attention and working memory domains distinguished the cognitively intact cluster from HCs. Longitudinally, the impaired group displayed a 'floor' effect, with no noticeable deterioration, but showed a \"catch-up\" trajectory in attention and working memory. This group had a higher conversion rate and more cases diagnosed with psychotic disorders than the intact group. In the intact group, converters exhibited a decline in attention and functioning. Most cognitive trajectories showed a positive relationship with functional outcomes.</p><p><strong>Conclusions: </strong>The study provides evidence for distinct cognitive subtypes in CHR, independent of conversion status. Early evaluation across cognitive domains is crucial for identifying trajectories to tailor interventions that aim to enhance outcomes for individuals at CHR for psychosis. Future research should focus on longer follow-up trajectories targeting attention and working memory and explore related intervention strategies.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144542055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reevaluating antipsychotic polypharmacy in schizophrenia: A broader perspective on social recovery.","authors":"Mohsin Raza, Javed Iqbal, Muna A Al-Maslamani","doi":"10.1111/pcn.13826","DOIUrl":"10.1111/pcn.13826","url":null,"abstract":"<p><p>This article relates to Reevaluating Antipsychotic Polypharmacy in Schizophrenia: A Broader Perspective on Social Recovery.</p>","PeriodicalId":20938,"journal":{"name":"Psychiatry and Clinical Neurosciences","volume":" ","pages":"429"},"PeriodicalIF":5.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}