Biological Psychiatry最新文献

{"title":"Task and resting state fMRI modelling of brain-behavior relationships in developmental cohorts.","authors":"Lucina Q Uddin, Hugh Garavan","doi":"10.1016/j.biopsych.2025.09.012","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.09.012","url":null,"abstract":"<p><p>Functional magnetic resonance imaging (fMRI) data are often used to inform individual differences in cognitive, behavioral, and psychiatric phenotypes. These so-called \"brain-behavior\" association studies come in many flavors and are increasingly the focus of investigations utilizing large population neuroscience datasets. Still, many open questions surrounding the utility of task and resting state fMRI for modelling brain-behavior relationships remain, including the feasibility of conducting these investigations in developmental cohorts. With the growing availability of large neurodevelopmental datasets such as that provided by the Adolescent Brain Cognitive Development (ABCD) Study, we are now able to conduct well-powered analyses using large samples of longitudinal neuroimaging data collected from diverse populations of youth. Here we provide a high-level review of current controversies and challenges in this growing subfield of neuroscience, highlighting examples where task fMRI data and resting state fMRI data - either in isolation or combined - have yielded significant insights into brain-behavior associations. Challenges include issues related to measurement noise, appropriate estimation of effect sizes, and limits to generalizability due to insufficient diversity of samples. Innovative solutions involving advanced MRI data acquisition protocols, application of multivariate analysis methods, and more robust consideration of phenotypic complexity are reviewed. We propose that additional future directions for developmental cognitive neuroscience should include more reliable behavioral measures, multimodal neuroimaging brain-behavior studies, and greater consideration of environmental and other contextual influences on brain-behavior associations.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Genetic Testing in Schizophrenia: A Systematic Review and Meta-Analysis.","authors":"Harman Singh Brah, Nimrat Sran, Sanjana Sanghani, Luke Valmadrid, Isabel Gandarilla, Savannah Fakhouri, Emma Longmire, Karen M Heskett, Kimberley Marie Kendall, Armin Raznahan, Danielle Baribeau, Chun Chieh Fan, Aaron D Besterman","doi":"10.1016/j.biopsych.2025.09.010","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.09.010","url":null,"abstract":"<p><strong>Background: </strong>Genetic testing may provide important diagnostic information for individuals with schizophrenia, but the frequency with which clinically significant variants are identified across different testing approaches has not been systematically evaluated.</p><p><strong>Methods: </strong>We conducted a systematic review and meta-analysis searching MEDLINE, EMBASE, and APA PsycINFO (January 2007-June 2023) for studies reporting results of clinical genetic testing in schizophrenia. Two independent reviewers performed abstract/title screening, full-text review, and data extraction following PRISMA guidelines. A random-effects model was used to estimate the pooled and platform-specific proportions of individuals with pathogenic or likely pathogenic variants, with heterogeneity assessed using the I² statistic.</p><p><strong>Results: </strong>Analysis of 31 studies (20,476 participants) showed that 6% (95% CI: 4% to 7%) of individuals with schizophrenia had a clinically significant genetic variant identified. Detection rates were 6% (95% CI: 4% to 8%) for chromosomal microarray, 5% (95% CI: -0.02% to 12%) for exome sequencing, and 7% (95% CI: 2% to 12%) for genome sequencing. Substantial heterogeneity was observed across studies (I² = 95.9%). Geographic representation was limited, with no studies from Latin America, South Asia, or Africa.</p><p><strong>Conclusions: </strong>Genetic testing identifies clinically informative variants in approximately 6% of individuals with schizophrenia. However, substantial heterogeneity across studies and limited geographic representation underscore the need for more standardized testing approaches and broader population sampling in future genetic research on schizophrenia.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic review and mega-analysis of the peripheral blood transcriptome in depression implicates dysregulation of lymphoid cells and histones.","authors":"Chaitanya Erady, Richard Bethlehem, Edward Bullmore, Mary-Ellen Lynall","doi":"10.1016/j.biopsych.2025.09.008","DOIUrl":"10.1016/j.biopsych.2025.09.008","url":null,"abstract":"<p><strong>Background: </strong>Depression has been associated with transcriptomic changes in peripheral blood. However, the contribution of specific immune cell subsets or pathways remains unclear, and findings have been variable across previous studies, which have not tended to account for sample cellular composition.</p><p><strong>Methods: </strong>We performed a systematic review of peripheral blood transcriptome studies in depression. For the five datasets meeting criteria (total N=6,011), we performed harmonized reprocessing and cell-composition-adjusted differential gene and transcript analyses, followed by a bias- and inflation-adjusted weighted Z-score mega-analysis. We investigated the biological pathways and cell subsets implicated by the results. We also performed a sex-stratified gene network mega-analysis using consensus weighted gene co-expression network analysis (WGCNA).</p><p><strong>Results: </strong>Few genes showed robust differential gene expression (DGE) in depression. Depression was reproducibly associated with decreases in replication-dependent histones, and with a decrease in oxidative phosphorylation pathways in females only. Cell source analyses implicated lymphoid cells (T cells and NK cells) as likely contributors to the depression differential expression signature. WGCNA mega-analysis revealed multiple consensus modules associated with depression, with a PUF60-related module upregulated in both female and male depression in sex-stratified analyses. Two genes predicted to be causally relevant to depression by transcriptome-wide association studies (GPX4 and GYPE) showed significant DGE.</p><p><strong>Conclusions: </strong>These results are convergent with immunogenetic evidence implicating lymphoid cell dysregulation in depression, while also highlighting histone alterations as a key molecular signature in depression. They also indicate the importance of large-scale datasets for biomarker discovery in the context of heterogeneous disorders like depression.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cannabidiol attenuates heroin seeking in male rats associated with normalization of discrete neurobiological signatures within the nucleus accumbens with subregional specificity.","authors":"Alexandra Chisholm, Jacqueline-Marie N Ferland, Randall J Ellis, Yasmin L Hurd","doi":"10.1016/j.biopsych.2025.08.023","DOIUrl":"https://doi.org/10.1016/j.biopsych.2025.08.023","url":null,"abstract":"<p><strong>Background: </strong>Opioid use disorder is a chronic relapsing condition characterized by cycles of compulsive drug use, abstinence, and relapse. Cannabidiol (CBD), a non-intoxicating cannabinoid, is under investigation as an anti-relapse treatment. CBD attenuates cue-induced heroin-seeking in a rodent model of relapse, and reduces craving and anxiety induced by drug-associated cues in abstinent individuals with heroin use disorder. The neurobiological mechanisms by which CBD may exert its anti-relapse effects are unknown.</p><p><strong>Methods: </strong>The objective of the current study was to evaluate the effects of CBD administration on heroin-seeking behavior in conjunction with transcriptomic profiling in the nucleus accumbens core (NAcC) and shell (NAcS).</p><p><strong>Results: </strong>Heroin-trained animals exhibited high levels of cue-induced heroin-seeking behavior. Importantly, CBD attenuated cue-induced heroin-seeking behaviors. Postmortem RNA-sequencing of the NAcC and NAcS revealed shared transcriptomic alterations the NAc subregions in response to heroin, with a more robust impact of heroin in the NAcS. Though CBD had minimal impact on the heroin-induced perturbations in the NAcC, it normalized components of the transcriptomic signature altered by heroin in both NAc subregions including transcripts that correlated with heroin-seeking behavior. In contrast, CBD normalized a particular subset of NAcS genes that correlated to heroin-seeking behavior. Those genes were specifically linked to the extracellular matrix, astrocyte function, and their upstream regulators related to immune function.</p><p><strong>Conclusion: </strong>These findings underscore the NAc subregional signatures of heroin-induced neurobiological perturbations and provide novel biological targets relevant for CBD's apparent anti-relapse effects.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic susceptibility to neurodevelopmental conditions associates with neonatal DNA methylation patterns in the general population: an individual participant data meta-analysis.","authors":"Isabel K Schuurmans, Dinka Smajlagic, Vilte Baltramonaityte, Anni L K Malmberg, Alexander Neumann, Nicole Creasey, Janine F Felix, Henning Tiemeier, Jean-Baptiste Pingault, Darina Czamara, Katri Raïkkönen, Chistian Magnus Page, Robert Lyle, Alexandra Havdahl, Jari Lahti, Esther Walton, Mona Bekkhus, Charlotte A M Cecil","doi":"10.1016/j.biopsych.2025.09.005","DOIUrl":"10.1016/j.biopsych.2025.09.005","url":null,"abstract":"<p><strong>Objective: </strong>Autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and schizophrenia (SCZ) are highly heritable and linked to disruptions in fetal neurodevelopment. Epigenetic processes, such as DNA methylation (DNAm), are considered a key pathway of interest. Yet, it is unclear whether: (i) genetic susceptibility to neurodevelopmental conditions associates with DNAm patterns already at birth; (ii) DNAm patterns are unique or shared across conditions, and (iii) neonatal DNAm patterns can be leveraged to enhance genetic prediction of neurodevelopmental outcomes.</p><p><strong>Methods: </strong>We conducted epigenome-wide meta-analyses of genetic susceptibility to ASD, ADHD, and schizophrenia (measured with polygenic scores [PGSs]) and cord blood DNAm in four European population-based cohorts (n_pooled=5,802; 50.2% female). We estimated DNAm pattern overlap between PGSs using heterogeneity statistics. Further, we built methylation profile scores for each PGS to test incremental variance explained over genetic data alone in 130 developmental outcomes from birth to 14 years.</p><p><strong>Results: </strong>In probe-level analyses, SCZ-PGS associated with neonatal DNAm at 246 loci (p<9x10^-8), predominantly in the major histocompatibility complex, supporting an early-origins perspective on schizophrenia. Functional characterization confirmed strong genetic effects, blood-brain concordance and enrichment for immune-related pathways. 8 loci were identified for ASD-PGS (mapping to FDFT1 and MFHAS1), and none for ADHD-PGS. Differentially methylated regions were detected across PGSs (130-166 regions). Overall, DNAm signals were largely distinct between conditions. Incorporating neonatal DNAm data in genetic prediction models nominally increased explained variance for several cognitive and motor outcomes.</p><p><strong>Conclusions: </strong>Genetic susceptibility for neurodevelopmental conditions, particularly schizophrenia, is detectable in cord blood DNAm in the general population.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.0,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Context Matters: Sex and Social Status Impact Cocaine’s Effects on Kappa Opioid Receptors","authors":"Yasmin Zakiniaeiz,&nbsp;Kelly Patricia Cosgrove","doi":"10.1016/j.biopsych.2025.07.019","DOIUrl":"10.1016/j.biopsych.2025.07.019","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"98 8","pages":"Pages 584-585"},"PeriodicalIF":9.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hevin Protein Links Cocaine-Evoked Astrocyte Calcium to Synaptic Strength and Reward Memory","authors":"Kathryn J. Reissner","doi":"10.1016/j.biopsych.2025.08.001","DOIUrl":"10.1016/j.biopsych.2025.08.001","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"98 8","pages":"Pages 582-583"},"PeriodicalIF":9.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","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/S0006-3223(25)01414-3","DOIUrl":"10.1016/S0006-3223(25)01414-3","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"98 8","pages":"Page A2"},"PeriodicalIF":9.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","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/S0006-3223(25)01417-9","DOIUrl":"10.1016/S0006-3223(25)01417-9","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"98 8","pages":"Pages A5-A10"},"PeriodicalIF":9.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145108125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intrinsic Deacetylation Represses Intrinsic Excitation: HDAC5 and Cocaine Substance Use Disorder","authors":"Elizabeth A. Heller","doi":"10.1016/j.biopsych.2025.08.002","DOIUrl":"10.1016/j.biopsych.2025.08.002","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"98 8","pages":"Pages 580-581"},"PeriodicalIF":9.0,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}