Biological Psychiatry最新文献

{"title":"Expression of Concern to: \"Gamma Secretase-Activating Protein Is a Substrate for Caspase-3: Implications for Alzheimer's Disease,\" by Chu et al. (Biol Psychiatry 2015; 77:720-728); https://doi.org/10.1016/j.biopsych.2014.06.003.","authors":"","doi":"10.1016/j.biopsych.2026.10.007","DOIUrl":"10.1016/j.biopsych.2026.10.007","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206516","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":"Neural Circuits of Social Behavior in Autism Spectrum Disorder: From Mechanism to Intervention.","authors":"Kally C O'Reilly Sparks, Ernest V Pedapati","doi":"10.1016/j.biopsych.2026.10.006","DOIUrl":"https://doi.org/10.1016/j.biopsych.2026.10.006","url":null,"abstract":"<p><strong>Introduction: </strong>Difficulties in social communication and interaction are core diagnostic features of autism spectrum disorder (ASD), yet interventions targeting these difficulties have modest and variable effects. Understanding mechanistically distinct contributions to social behaviors may identify new therapeutic opportunities.</p><p><strong>Methods: </strong>This narrative review integrates human neuroimaging studies, supporting rodent circuit neuroscience, clinical intervention research, and developmental studies. We organize the findings into four overlapping functional-computational domains and relate these domains to the Research Domain Criteria Social Processes framework.</p><p><strong>Results: </strong>The four domains are: (1) Social Reward and Social Interest, encompassing the incentive and hedonic value of social contact and motivation to engage; (2) Social Memory and Social-Affective Value, encompassing recognition of familiar individuals and learned affective or motivational associations; (3) Social Cue Perception, Action Representation, and Social Prediction/Timing, encompassing the processing and forecasting of dynamic social information; and (4) Higher-Order Social Cognition and Model Updating, encompassing mental-state inference and the updating of person-specific social models. Because these domains are not independent, interactions among reward, memory, cue processing, prediction, and higher-order inference create multiple possible developmental entry points, such that early differences in one process may alter experience-dependent learning in others. Evidence for specific causal cascades remains preliminary and requires longitudinal testing.</p><p><strong>Conclusions: </strong>A circuit-and-development framework may improve hypothesis generation, domain-specific phenotyping, target-engagement assessment, and mechanism-aligned outcomes. Clinical translation, however, requires caution. Biomarkers should be validated as predictors of treatment response, cascade models should be tested longitudinally, and interventions should combine mechanism-informed targets with behavioral support that promotes generalization to daily life.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179310","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":"Erratum to: Triple Interactions Between the Environment, Brain, and Behavior in Children: An ABCD Study.","authors":"","doi":"10.1016/j.biopsych.2026.09.015","DOIUrl":"https://doi.org/10.1016/j.biopsych.2026.09.015","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179291","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 architecture and risk of suicide attempt across neurodevelopmental and psychiatric conditions.","authors":"Anna Starnawska, Trine Tollerup Nielsen, Jakob Grove, Juan Cordero-Solorzano, Jonas Bybjerg-Grauholm, Elizabeth C Corfield, Richard J L Anney, Anna R Docherty, Anders D Børglum, Ditte Demontis","doi":"10.1016/j.biopsych.2026.09.028","DOIUrl":"https://doi.org/10.1016/j.biopsych.2026.09.028","url":null,"abstract":"<p><strong>Background: </strong>Suicide attempt (SA) is prevalent among individuals with neurodevelopmental and psychiatric conditions, yet similarities and differences in the genetic architecture of SA across these conditions remain unclear.</p><p><strong>Methods: </strong>In the iPSYCH cohort (N=98,069), SA was identified using ICD-10 codes among individuals diagnosed with attention-deficit hyperactivity disorder (ADHD) (N=22,962), autism (N=17,670), schizophrenia (N=5,974), bipolar disorder (N=3,028), depression (N=28,844), and controls (N=34,049). We evaluated 21 polygenic scores (PGSs) in individuals with and without SA within each diagnosis, stratified individuals into PGS quantiles, estimated absolute SA risk, and conducted sex-stratified analyses.</p><p><strong>Results: </strong>SA was 1% among controls but ranged from 5% in autism to 31% in schizophrenia. Several PGSs were increased in individuals with SA across diagnoses, including PGS for ADHD, depression, and substance use disorders (SUD). SA-PGS stratification showed marked SA absolute risk differences, e.g., 40% in the top PGS tertile vs 29% in the lowest tertile in schizophrenia. PGS-loads did not differ between females and males with SA across diagnoses. However, absolute SA risk differed substantially. In the highest SA-PGS tertile in ADHD, the absolute SA risk reached 36% for females and 22% for males and was further increased to 48% in those with comorbid SUD.</p><p><strong>Conclusions: </strong>SA genetic architecture is similar across neurodevelopmental and psychiatric conditions and individuals can be stratified into SA risk groups based on PGSs, and co-occuring SUD. Being a female or having comorbid SUD are strong risk factors for SA, however SA common variants, still affect SA risk in the presence of those factors.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179261","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":"Development of a messenger RNA therapy for schizophrenia.","authors":"Nicole W Simons, Vibhuti Patel, Haoyuan Li, Shruti Iyer, Yichen Zhong, Dinglingge Cao, Changyue Yu, Deborah Obiajulu, Katherine Keller, Gavin Hynes, Simon Lee, Rajiv Nadukuru, Esther Cheng, Earnest P Chen, Alice Hashemi, Anina N Lund, Henry C Rogers, Rachel Jackson, Michael Preuss, Heather Thibeau, Girish N Nadkarni, Lora E Liharska, Dennis S Charney, Mafalda Barbosa, Samuele G Marro, René S Kahn, Nan Yang, Yizhou Dong, Alexander W Charney","doi":"10.1016/j.biopsych.2026.10.004","DOIUrl":"https://doi.org/10.1016/j.biopsych.2026.10.004","url":null,"abstract":"<p><strong>Background: </strong>Few gene-disease associations identified by human genetic studies lead to new drugs that advance to first-in-human trials. Schizophrenia exemplifies this translational gap: thousands of gene-disease associations have been reported, but antipsychotics act via mechanisms introduced in the 1950s. To close the gap, clinical research strategies are needed that generalize across genes and diseases.</p><p><strong>Methods: </strong>Candidate drug targets were defined as genes linked to schizophrenia by population-based studies. Clinical validation of candidate targets was performed through family-based studies. The molecular effects of clinically validated targets were confirmed by correcting mutations in the neurons from affected family members. For one validated target, a messenger RNA (mRNA) drug was developed, and pre-clinical studies of the drug were performed.</p><p><strong>Results: </strong>Carriers of rare protein-truncating variants (PTVs) in schizophrenia risk genes were identified in 30,813 patients of a US healthcare system. These included two female relatives with a rare PTV in GRIA3, which encodes the GluA3 subunit of the AMPA-type glutamate receptor. Further investigation of the family found an X-linked pattern of inheritance between the PTV and severe mental illness. Correction of the PTV in neurons of affected male family members restored GRIA3 expression. A GRIA3 mRNA drug was developed and in mice was well tolerated, resulted in broad brain expression of GluA3, and rescued behavioral abnormalities in a pharmacologically induced psychosis model (MK-801).</p><p><strong>Conclusions: </strong>Further development toward clinical evaluation of a novel GRIA3 mRNA drug to treat schizophrenia is warranted.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163906","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":"Excitation-Inhibition Balance and Fronto-Limbic Connectivity Distinguish TMS Treatment Outcomes in Refractory Depression.","authors":"Davide Momi, Zheng Wang, Mohammad P Oveisi, Kevin Kadak, Sorenza P Bastiaens, Jennifer I Lissemore, Yoshihiro Noda, Jonathan Downar, Fidel Vila Rodriguez, Rebecca Strafella, Zafiris J Daskalakis, Christoph Zrenner, Reza Zomorrodi, Camarin E Rolle, Manish Saggar, Nolan Williams, Corey J Keller, Daniel M Blumberger, Daphne Voineskos, John D Griffiths","doi":"10.1016/j.biopsych.2026.09.027","DOIUrl":"https://doi.org/10.1016/j.biopsych.2026.09.027","url":null,"abstract":"<p><strong>Background: </strong>Intermittent theta burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex (DLPFC) is effective for treatment-resistant depression, but outcomes remain variable. The neurophysiological mechanisms underlying response remain poorly understood, limiting precision neuromodulation.</p><p><strong>Methods: </strong>We combined transcranial magnetic stimulation with electroencephalography (TMS-EEG) and connectome-based Jansen-Rit neural mass modeling to investigate the mechanistic basis of treatment efficacy in 90 patients with treatment-resistant depression. Individualized whole-brain models were fitted to pre- and post-iTBS TMS-evoked potentials, yielding subject-specific estimates of synaptic connectivity, excitation-inhibition (E/I) balance, and cortical dynamics. Brain states were defined by singular value decomposition of the model's population activity, and partial least squares analysis with nested cross-validation identified the brain-state pattern distinguishing responders from non-responders.</p><p><strong>Results: </strong>We identified two neurophysiological signatures associated with treatment response. First, responders showed greater post-treatment reductions in 3-10 Hz oscillatory power, driven by shifts in E/I balance toward greater inhibitory control through reduced excitatory drive and increased inhibitory-to-pyramidal connectivity. Second, a pre-treatment brain state characterized by opposite-polarity dynamics between subgenual anterior cingulate cortex (sgACC) and left DLPFC distinguished responders from non-responders, consistent with prior fMRI findings on frontolimbic anticorrelation. Neural trajectory analysis further revealed greater dynamical reorganization and increased attractor stability in responders following treatment.</p><p><strong>Conclusions: </strong>These findings provide a neurophysiologically-informed framework linking iTBS treatment efficacy to specific changes in cortical E/I balance and frontolimbic circuit dynamics, pointing toward candidate markers that, with subject-specific structural connectivity and independent validation, may inform personalized neuromodulation approaches in treatment-resistant depression.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164111","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":"The genetic orchestra of autism and its intersections with epilepsy, intellectual disability, and ADHD.","authors":"Sélin Korkmaz, Jean-Madeleine De Sainte Agathe, Freddy Cliquet, L Caitlin Martin, Eli Barthome, Mathis Fleury, Julie Segers, Stéf Bonnot-Briey, Vincent Grimaldi de Puget, Yanlin Zhou, Dieter Wolke, Jakob Grove, Anders D Børglum, Richard Delorme, Claire S Leblond, Thomas Bourgeron","doi":"10.1016/j.biopsych.2026.10.003","DOIUrl":"https://doi.org/10.1016/j.biopsych.2026.10.003","url":null,"abstract":"<p><p>Autism is a complex condition with marked phenotypic variability and a multifactorial etiology orchestrated by diverse genetic and environmental influences. In this review, we dissect what we refer to as autism's \"genetic orchestra\", spanning from the high-impact \"soloists\", de novo and ultra-rare variants with large effect sizes, to the \"polyphonic background\" of common variants which individually exert modest effects but collectively have significant impact. We examine how this orchestra wires neural circuits, with convergent biological pathways modulating synaptic function and chromatin remodeling. Although de novo, rare, and common variants are often studied independently, converging evidence supports a model whereby their influences are largely additive. This genetic orchestra is not condition-specific; autism frequently co-occurs with other neurodevelopmental and psychiatric conditions, reflecting substantial pleiotropy across both rare and common variant landscapes. Notably, ultra-rare variants tend to associate with co-occurring intellectual disability, ADHD, epilepsy, and psychiatric conditions highlighting their high phenotypic impact. Beyond genetics, layers of environmental and contextual factors further modulate clinical outcomes. In this framework, we also discuss the challenges of identifying genetic variants associated with autism through clinical genetic testing, where yields remain context-dependent, varying by sex and co-occurring conditions. Finally, we address current limitations and future directions in refining our understanding of autism's genetic basis.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.3,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147335","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":"Connection-Level Multi-Omics Reveals Cerebellar-Cortical Dysconnectivity and Divergent Molecular Signatures Across Major Psychiatric Disorders","authors":"Yunheng Diao,Yuanyuan Huang,Baoyuan Zhu,Minxin Guo,Wei Wang,Zhaobo Li,Xin Zhang,Kai Li,Wenhao Li,Hongyu Wang,Jing Zhou,Xiaobo Li,Fengchun Wu,Kai Wu","doi":"10.1016/j.biopsych.2026.09.020","DOIUrl":"https://doi.org/10.1016/j.biopsych.2026.09.020","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"22 1","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088958","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":"Sleep and Drug Use: Neuroimaging Evidence for a Multidimensional Brain Framework","authors":"Rui Zhang,Nora D. Volkow","doi":"10.1016/j.biopsych.2026.09.024","DOIUrl":"https://doi.org/10.1016/j.biopsych.2026.09.024","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"36 1","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088959","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":"TMS-Evoked Cortical Reactivity Signatures as a Multidimensional Biomarker of Depression: A TMS-EEG Meta-Analysis from Diagnosis to Prognosis","authors":"Ji-Yu Xie,Tao Zhao,Liang Guo,Dong Li,Yanjie Zhao,Zhimin Wang,Pengfei Wang,Linghui Meng,Gang Wang,Zhi Yang","doi":"10.1016/j.biopsych.2026.09.022","DOIUrl":"https://doi.org/10.1016/j.biopsych.2026.09.022","url":null,"abstract":"","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":"48 1","pages":""},"PeriodicalIF":10.6,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088961","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}