Biological psychiatry global open science最新文献

{"title":"Mineralocorticoid Receptor in Glutamatergic Neurons Modulates Anxiety Exclusively in Male Mice Via Regulation of the Actin-Bundling Factor Fam107a","authors":"Huanqing Yang ,&nbsp;Sowmya Narayan ,&nbsp;Joeri Bordes ,&nbsp;Lotte van Doeselaar ,&nbsp;Carlo De Donno ,&nbsp;Matthias Eder ,&nbsp;Danusa Menegaz ,&nbsp;Rosa-Eva Huettl ,&nbsp;Lea-Maria Brix ,&nbsp;Shiladitya Mitra ,&nbsp;Margherita Springer ,&nbsp;Marianne B. Müller ,&nbsp;Alon Chen ,&nbsp;Jan M. Deussing ,&nbsp;Juan Pablo Lopez ,&nbsp;Mathias V. Schmidt","doi":"10.1016/j.bpsgos.2025.100651","DOIUrl":"10.1016/j.bpsgos.2025.100651","url":null,"abstract":"<div><h3>Background</h3><div>Exposure to stressful life events is a major risk factor for many psychiatric disorders. The mineralocorticoid receptor (MR) is a key regulator of the hypothalamic-pituitary-adrenal axis, a central stress response component. Stress-related mental disorders, such as anxiety and depression, are associated with MR dysfunction in the brain, but its cell type–specific contributions to emotional behavior and cognitive function remain unclear.</div></div><div><h3>Methods</h3><div>Using a mouse model with a specific deletion of MR in forebrain glutamatergic neurons, we tested the behavioral, structural, and functional impact of MR in this neuronal population (<em>n</em> = 9–14 for behavioral and <em>n</em> = 3–4 for structural and functional analyses).</div></div><div><h3>Results</h3><div>We revealed a specific function of MR in regulating baseline anxiety in male but not female mice. This distinct behavioral phenotype was associated with hippocampal structural and functional alterations. Furthermore, we identified a previously unrecognized downstream target of MR, the actin-bundling factor Fam107a, whose expression is tightly regulated by MR. Overexpression of Fam107a in the hippocampus was sufficient to rescue the increased anxiety phenotype of glutamatergic MR knockout mice.</div></div><div><h3>Conclusions</h3><div>Together, our results underline the central role of MR as a potential target in understanding the intricate interplay between stress, resilience, and mental health.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100651"},"PeriodicalIF":3.7,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145885178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engagement of the Paraventricular Nucleus of the Thalamus During Withdrawal-Related Learning: Implications for Alcohol Use Disorder","authors":"Laureta Gashi ,&nbsp;Sophia Khom","doi":"10.1016/j.bpsgos.2025.100621","DOIUrl":"10.1016/j.bpsgos.2025.100621","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 1","pages":"Article 100621"},"PeriodicalIF":3.7,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145467528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial Board Page","authors":"","doi":"10.1016/S2667-1743(25)00187-9","DOIUrl":"10.1016/S2667-1743(25)00187-9","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100633"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145519747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acknowledgments","authors":"","doi":"10.1016/j.bpsgos.2025.100630","DOIUrl":"10.1016/j.bpsgos.2025.100630","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100630"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145519746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subscribers Page","authors":"","doi":"10.1016/S2667-1743(25)00188-0","DOIUrl":"10.1016/S2667-1743(25)00188-0","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100634"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145519748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guide for Authors","authors":"","doi":"10.1016/S2667-1743(25)00190-9","DOIUrl":"10.1016/S2667-1743(25)00190-9","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"5 6","pages":"Article 100636"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145519745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased Tumor Necrosis Factor Superfamily Members in Neuroinflammatory Schizophrenia and Bipolar Disorder Midbrains","authors":"Gerardo Mendez-Victoriano ,&nbsp;Yunting Zhu ,&nbsp;Layla Neuhaus ,&nbsp;Suhaana Shaik ,&nbsp;Frank Middleton ,&nbsp;Yuji Kondo ,&nbsp;Amir Fayyazuddin ,&nbsp;Daniel Hoeppner ,&nbsp;Sofía Puvogel ,&nbsp;Astrid Alsema ,&nbsp;Laura Kracht ,&nbsp;Mitsuyuki Matsumoto ,&nbsp;Bart J.L. Eggen ,&nbsp;Adam K. Walker ,&nbsp;Maree J. Webster ,&nbsp;Iris E.C. Sommer ,&nbsp;Cynthia S. Weickert","doi":"10.1016/j.bpsgos.2025.100650","DOIUrl":"10.1016/j.bpsgos.2025.100650","url":null,"abstract":"<div><h3>Background</h3><div>Neuroinflammation is a key neuropathological finding in schizophrenia and bipolar disorder, as increased cytokines are found in the midbrain of these individuals. However, the most upregulated inflammatory cytokines and most activated downstream signaling pathway(s) are unidentified.</div></div><div><h3>Methods</h3><div>We aimed to identify the most robust transcriptional change in the schizophrenia midbrain by bulk RNA sequencing (RNA-seq) and to confirm the cellular source and magnitude of change by single-nucleus RNA-seq, reverse transcriptase–polymerase chain reaction (RT-PCR), and immunohistochemistry in 61 healthy controls, 63 schizophrenia cases, and 33 bipolar disorder cases stratified into low- and high-inflammation groups.</div></div><div><h3>Results</h3><div>By RNA-seq, the TNF superfamily (TNFSF) pathway messenger RNAs (mRNAs) were among the most changed in high-inflammation schizophrenia (all <em>p</em>s ≤ .01), with TNFSF receptors (<em>TNFR1</em>, <em>TNFR2</em>, and <em>FAS</em>) being most highly expressed in astrocytes and microglia. Using RT-PCR, we confirmed that 5 TNFSF receptor mRNAs (<em>TNFR</em><em>1</em>, <em>TNFR</em><em>2</em>, <em>DR4</em>, <em>FAS</em>, and <em>TWEAKR</em>, all <em>p</em>s ≤ .01) were increased in high-inflammation schizophrenia/bipolar disorder cases compared with low-inflammation controls. Furthermore, the means for mRNA encoding cell death–related proteins acting downstream of TNF receptors (<em>P53</em>, <em>CASP1</em>, <em>CASP7</em>, <em>CASP8</em>; all <em>p</em>s ≤ .05) were increased in high-inflammation schizophrenia, as were mRNAs encoding proteins regulating cell survival (<em>BCL2</em> and <em>MCL1</em>, all <em>p</em>s ≤ .01). All 5 TNFSF receptor mRNAs positively correlated with effector protein mRNAs (all <em>p</em>s ≤ .05) and with the astrocyte-related marker <em>GFAP</em> mRNA (all <em>p</em>s ≤ .001).</div></div><div><h3>Conclusions</h3><div>Our results suggest that TNFSF transcripts represent the main activated inflammatory pathway in the midbrains of people with schizophrenia, which overlaps somewhat with bipolar disorder. These findings highlight the need for anti-inflammatory interventions targeting TNF/TNFSF receptors to test for therapeutic benefits in psychiatric patients displaying elevated inflammation.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100650"},"PeriodicalIF":3.7,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistent Alterations of Brain and Behavior in Children With Low Prenatal Alcohol Exposure","authors":"Xiangyu Long ,&nbsp;Catherine Lebel","doi":"10.1016/j.bpsgos.2025.100648","DOIUrl":"10.1016/j.bpsgos.2025.100648","url":null,"abstract":"<div><h3>Background</h3><div>Heavy prenatal alcohol exposure (PAE) is associated with alterations in behavior and cognitive and brain development. However, the effects of low levels of PAE on the brain and behavior remain unclear. In the current study, we aimed to investigate longitudinal changes in the brain and behavior in children with low levels of PAE compared with well-matched unexposed children.</div></div><div><h3>Methods</h3><div>Children (<em>n</em> = 108, mean [SD] = 9.52 [0.50] years at baseline) with PAE (0.97 ± 0.90 drinks/wk) and control children (<em>n</em> = 108, 9.52 [0.50] years at baseline) matched on socioeconomic status were selected from the ABCD (Adolescent Brain Cognitive Development) Study and were followed over 4 years with magnetic resonance imaging and Child Behavior Checklist (CBCL) scores. No children had adverse exposures to other substances.</div></div><div><h3>Results</h3><div>Compared with unexposed children, children with low levels of PAE had persistently higher CBCL scores (worse behavior) and higher intracranial volumes over time.</div></div><div><h3>Conclusions</h3><div>Our results provide further evidence of alterations in the brain and behavior associated with low levels of PAE across early adolescence, highlighting the importance of prevention and early intervention even with low levels of PAE.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100648"},"PeriodicalIF":3.7,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145885174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Socioeconomic Status Is Associated With Reward Processing, Interleukin 1β, Striatal Connectivity, and Antidepressant Outcomes in Individuals With Major Depressive Disorder: A CAN-BIND-1 Report","authors":"Sara Jani ,&nbsp;Stefanie Hassel ,&nbsp;Jane A. Foster ,&nbsp;Gustavo Turecki ,&nbsp;Nicholas Bock ,&nbsp;Nathan Churchill ,&nbsp;Daniel J. Mueller ,&nbsp;Raymond W. Lam ,&nbsp;Valerie H. Taylor ,&nbsp;Roumen Milev ,&nbsp;Claudio Soares ,&nbsp;Susan Rotzinger ,&nbsp;Sakina J. Rizvi ,&nbsp;Sidney H. Kennedy ,&nbsp;Benicio N. Frey ,&nbsp;Katharine Dunlop","doi":"10.1016/j.bpsgos.2025.100649","DOIUrl":"10.1016/j.bpsgos.2025.100649","url":null,"abstract":"<div><h3>Background</h3><div>Major depressive disorder (MDD) is a common condition with heterogeneous risk factors. Socioeconomic status (SES) is one such risk factor, which is negatively linked to MDD treatment outcomes and symptom severity. SES is associated with altered resting-state functional connectivity (RSFC) in reward-processing circuitry and elevated proinflammatory cytokine levels in individuals without depression. However, how the negative consequences of low SES exacerbate MDD psychopathology is poorly understood.</div></div><div><h3>Methods</h3><div>Data on SES (household income and education), depression severity, self-reported reward processing, serum proinflammatory cytokine levels, and neuroimaging for 323 adult participants (211 patients with MDD receiving open-label escitalopram, 112 control participants without depression; 63.4% female) were obtained from the CAN-BIND-1 (Canadian Biomarker Integration in Depression Study-1) dataset. General linear models assessed the effects of MDD diagnosis and SES on self-reported reward processing and proinflammatory cytokine levels. Whole-brain seed-to-voxel RSFC analyses were performed for the dorsal and ventral striatum leveraging 249 participants (150 patients with MDD, 99 control participants; 62.2% female). We also assessed the impact of SES on response to open-label escitalopram.</div></div><div><h3>Results</h3><div>Participants with MDD from households with lower incomes displayed lower goal pursuit behaviors, decreased interleukin 1β levels, and slower improvement to escitalopram relative to those from households with higher incomes. Using a lenient <em>z</em> &gt; 2.3 threshold, MDD household income correlated with striatal RSFC with the dorsolateral prefrontal and posterior cingulate cortices.</div></div><div><h3>Conclusions</h3><div>Our results elucidate the role of SES and its negative consequences in altering reward processing and antidepressant treatment efficacy in MDD, corroborating previous literature suggesting that SES significantly impacts health outcomes. Better characterizing the relationship between SES and MDD psychopathology may inform future treatment approaches and intervention development.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100649"},"PeriodicalIF":3.7,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Pubertal Development Is a Risk Factor for Psychotic-Like Experiences in Boys and Girls","authors":"Eric R. Larson ,&nbsp;Natasha Chaku ,&nbsp;Alexandra Moussa-Tooks","doi":"10.1016/j.bpsgos.2025.100647","DOIUrl":"10.1016/j.bpsgos.2025.100647","url":null,"abstract":"<div><h3>Background</h3><div>Puberty has long been identified as a risk factor for psychosis, although retrospective, cross-sectional, and single-sex indicators of puberty have limited our ability to pinpoint biopsychosocial mechanisms contributing to risk. The current study determined whether individual differences in the timing (onset) and tempo (pace) of pubertal development conferred risk for psychotic-like experiences (PLEs) in youth across biological sex.</div></div><div><h3>Methods</h3><div>Data included 11,758 youths (6134 boys and 5624 girls) from the ABCD (Adolescent Brain Cognitive Development) Study (average age = 9.9 years at baseline, 12.9 years at 3-year follow-up). Pubertal timing and tempo (overall, adrenarche, gonadarche) were derived from sex-specific linear mixed-effects models using the Pubertal Development Scale. Sex-specific negative binomial multilevel models estimated effects of categorical and continuously measured pubertal timing and tempo and their interaction on year-3 PLEs per the Prodromal Questionnaire-Brief Child.</div></div><div><h3>Results</h3><div>In both sexes, earlier pubertal timing was associated with elevated PLEs (βs = 0.23 to 0.31), and later pubertal timing was associated with fewer PLEs (βs = −0.22 to −0.52) relative to on-time peers. In boys only, faster pubertal tempo was associated with fewer PLEs relative to on-track peers (βs = −0.21 to −0.30). Analyses with continuous pubertal timing and tempo demonstrated an association between earlier adrenarchal timing and more PLEs in girls only (β = −0.21) and an interaction between adrenarchal timing and tempo in boys only (β = −0.80).</div></div><div><h3>Conclusions</h3><div>Early pubertal timing in both sexes and faster pubertal tempo in males increases PLEs. Understanding the unique experiences associated with a youth’s pubertal maturation, particularly adrenarche, can advance identification and prevention efforts for children and adolescents at greatest clinical risk.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100647"},"PeriodicalIF":3.7,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145841259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}