Biological psychiatry global open science最新文献

{"title":"Has Deep Brain Stimulation Shown Its Full Potential in Treatment-Resistant Depression? A Scoping Review","authors":"Liene Puke ,&nbsp;Joelle Rosselet Amoussou ,&nbsp;Armin von Gunten ,&nbsp;Julien Elowe","doi":"10.1016/j.bpsgos.2025.100682","DOIUrl":"10.1016/j.bpsgos.2025.100682","url":null,"abstract":"<div><div>Major depressive disorder is increasingly conceptualized as a networkopathy involving dysfunction across brain networks rather than isolated regions. This perspective has supported the use of deep brain stimulation (DBS) in treatment-resistant depression (TRD), where conventional therapies have failed. In this scoping review, we examined peer-reviewed studies on bilateral DBS for TRD, with a focus on the relationship between stimulation targets, conceptual frameworks of depression, and clinical outcome measures. A comprehensive literature search was conducted in September 2024 across 6 bibliographic databases, supplemented by citation tracking strategies to identify additional relevant studies. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, we screened and selected studies based on predefined eligibility criteria. The review identified significant variability in how TRD is defined, which brain targets are selected, and how these are associated with specific symptom dimensions. Anatomical targets varied widely, reflecting differing neurobiological rationales. While most studies assessed symptom severity using standardized scales such as the Montgomery–Åsberg Depression Rating Scale or Hamilton Depression Rating Scale, a minority of studies (8 of 48 [16.7%]) did not specify which symptom dimensions were expected to respond to DBS. Despite methodological heterogeneity, DBS appears promising for symptom alleviation in TRD. However, its clinical benefits remain to be fully established. The review highlights the need for greater standardization, including consistent definitions of TRD, clear symptom mapping, and improved integration of patient-reported and functional outcomes. Although most existing studies focus on bilateral stimulation, future work should also explore unilateral and multitarget approaches to advance toward more personalized neuromodulation strategies.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 3","pages":"Article 100682"},"PeriodicalIF":3.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146193183","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":"Causal Effects of Enhanced Parenting on Resting-State Graph Properties of Adolescents at Risk for Maltreatment","authors":"Marta Korom ,&nbsp;Mary Dozier ,&nbsp;Hung-Wei Bernie Chen ,&nbsp;Elisa Macera ,&nbsp;Nim Tottenham ,&nbsp;Jeffrey M. Spielberg","doi":"10.1016/j.bpsgos.2025.100646","DOIUrl":"10.1016/j.bpsgos.2025.100646","url":null,"abstract":"<div><h3>Background</h3><div>In this study, we investigated the sustained causal effects of enhanced early caregiving quality on adolescent brain network properties approximately 11 years after families received an attachment-based parenting intervention.</div></div><div><h3>Methods</h3><div>Participants included 60 adolescents whose parents were referred by Child Protective Services (CPS) because of risk for child maltreatment and 35 adolescents from families without a CPS history (total <em>N</em> = 95). CPS-involved families were randomly assigned to either the target intervention (Attachment and Biobehavioral Catch-up [ABC]) (<em>n</em> = 31) or a control intervention (Developmental Education for Families [DEF]) (<em>n</em> = 29) before the infants turned 2. During adolescence (mean_age = 13.4 years, SD = 0.37), participants underwent a 6-minute resting-state functional magnetic resonance imaging scan.</div></div><div><h3>Results</h3><div>Graph-theoretical analyses were completed with intervention status as the group-level predictor of interest. Adolescents who received the ABC intervention exhibited distinct global and local network properties compared with the DEF group. The ABC group demonstrated lower current-flow global efficiency and more hierarchical structure, indicating intervention-driven modulation of connectome-wide neurodevelopmental outcomes. Node-specific analyses also indicated intervention effects on clustering coefficients and communicability distances in frontal, limbic, and parietal cortices, suggesting nuanced effects of early interventions on local network properties. Exploratory moderation analyses revealed associations between brain network metrics and externalizing symptoms in the DEF group—indicative of neurobiological risk—that were absent in the ABC and low-risk groups.</div></div><div><h3>Conclusions</h3><div>The results suggest that the ABC intervention causally shapes the development of the resting-state connectome and associated regulatory health, offering insights into the neural pathways through which early enhanced care may get under the skin of at-risk adolescents.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100646"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145939221","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":"Lower Gyrification of the Ventromedial Prefrontal Cortex in Posttraumatic Stress Disorder: An ENIGMA-PTSD Study","authors":"Ahmed Hussain ,&nbsp;C. Lexi Baird ,&nbsp;Ashley A. Huggins ,&nbsp;Courtney C. Russell ,&nbsp;Delin Sun ,&nbsp;Leonel Rangel-Jimenez ,&nbsp;Chadi G. Abdallah ,&nbsp;Michael Angstadt ,&nbsp;Geoffrey May ,&nbsp;Hannah Berg ,&nbsp;Jennifer U. Blackford ,&nbsp;Josh Cisler ,&nbsp;Judith K. Daniels ,&nbsp;Nicholas D. Davenport ,&nbsp;Richard J. Davidson ,&nbsp;Maria Densmore ,&nbsp;Seth G. Disner ,&nbsp;Wissam El-Hage ,&nbsp;Amit Etkin ,&nbsp;Negar Fani ,&nbsp;Rajendra A. Morey","doi":"10.1016/j.bpsgos.2025.100679","DOIUrl":"10.1016/j.bpsgos.2025.100679","url":null,"abstract":"<div><h3>Background</h3><div>Cortical gyrification involves the formation of folds in the cerebral cortex, coinciding with key neurodevelopmental processes. Its strong correlation with increased cortical surface area and decreased cortical thickness may improve cortical signaling efficiency by decreasing cortico-cortical distance. Differences in brain structure have been found in posttraumatic stress disorder (PTSD), yet few small studies have examined cortical gyrification.</div></div><div><h3>Methods</h3><div>Gyrification was quantified using FreeSurfer’s Local Gyrification Index (lGI), derived from 3-dimensional T1-weighted volumetric brain magnetic resonance imaging in 1876 participants (PTSD <em>n</em> = 789, control <em>n</em> = 1087) across 24 sites from the ENIGMA-PGC (Enhancing Neuro Imaging Genetics through Meta-Analysis and Psychiatric Genomics Consortium) PTSD working group. Using a region of interest–based approach, we fitted a linear mixed-effects model with age (mean = 35.6, SD = 9.23, range = 8–95), sex (female = 967 [52%], male = 909 [48%]), pial surface area, PTSD, and random site effects to test associations between PTSD diagnosis/severity and regional lGI. We examined moderating effects of depression, childhood trauma, age, and sex.</div></div><div><h3>Results</h3><div>PTSD diagnosis and severity were both associated with lower lGI for the right medial orbitofrontal and right rostral anterior cingulate cortices. The interaction of PTSD and age was associated with lower lGI for the rostral middle frontal cortex bilaterally. Contrasting comorbid PTSD and major depressive disorder with the PTSD-only group showed that comorbidity was associated with lower lGI in the left inferior and medial temporal cortices.</div></div><div><h3>Conclusions</h3><div>Lower lGI, which is associated with impaired signaling efficiency, was observed in the PTSD group compared with the control group for the ventromedial prefrontal cortex, a region that has been strongly implicated in associative fear learning and extinction. It is possible that PTSD accelerates the typical age-associated decline in lGI of the rostral middle frontal cortices.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100679"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146183654","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":"Motivational Significance of Control Failures as a Window on Risk for Problematic Alcohol Involvement","authors":"Bruce D. Bartholow","doi":"10.1016/j.bpsgos.2025.100658","DOIUrl":"10.1016/j.bpsgos.2025.100658","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100658"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145798697","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":"Brain State Dynamics in Ketamine-Induced Dissociation Resemble Those in Posttraumatic Stress Disorder","authors":"Noam Goldway ,&nbsp;Taly Markovits ,&nbsp;Naomi Fine ,&nbsp;Tom Fruchtman-Steinbok ,&nbsp;Guy Gurevitch ,&nbsp;Gustavo Deco ,&nbsp;Haggai Sharon ,&nbsp;Talma Hendler","doi":"10.1016/j.bpsgos.2025.100655","DOIUrl":"10.1016/j.bpsgos.2025.100655","url":null,"abstract":"<div><h3>Background</h3><div>Dissociation, an altered state of consciousness in which individuals feel detached from their body, environment, and sense of self, is a common feature of posttraumatic stress disorder (PTSD). Despite its significance, the neurocognitive processes underlying dissociation remain poorly understood, potentially limiting diagnostic precision and treatment efficacy in PTSD.</div></div><div><h3>Methods</h3><div>To address this gap, we applied network control theory to resting-state functional magnetic resonance imaging to examine neural dynamics during dissociative states in 2 contexts: healthy volunteers (<em>n</em> = 30) undergoing intravenous administration of ketamine, an anesthetic known to induce dissociative states, and patients with PTSD receiving an intervention aimed at alleviating dissociative symptoms (a secondary analysis of data from 78 patients who participated in previously conducted clinical trials).</div></div><div><h3>Results</h3><div>Ketamine administration led to resting-state brain dynamics resembling those observed in patients with PTSD before treatment, characterized by an increased dominance of a default mode network (DMN) meta-state and a decreased dominance of a somatomotor network (SOM) meta-state. Posttreatment reduction in the dominance of the DMN meta-state correlated with a decrease in dissociative symptoms in patients with PTSD. Computational modeling analysis revealed that after treatment, patients with PTSD exhibited a more organized and less entropic brain state. However, contrary to our hypothesis, ketamine administration did not lead to significant changes in these entropy-related indices.</div></div><div><h3>Conclusions</h3><div>Dissociative states, whether induced by pharmacological manipulation or clinical condition, are accompanied by increased dominance of the DMN meta-state and reduced dominance of the SOM meta-state.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100655"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145885158","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":"Stress History Modulates Corticotropin-Releasing Factor Neurons to Establish Resilience","authors":"Sherod E. Haynes ,&nbsp;Anthony Lacagnina ,&nbsp;Hyun Seong Seo ,&nbsp;Fang Li ,&nbsp;Xiao Yang ,&nbsp;Muhammad Furqan Afzal ,&nbsp;Carole Morel ,&nbsp;Aurelie Menigoz ,&nbsp;Kanaka Rajan ,&nbsp;Roger L. Clem ,&nbsp;Barbara Juarez ,&nbsp;Helen S. Mayberg ,&nbsp;Donald G. Rainnie ,&nbsp;Larry J. Young ,&nbsp;Ming-Hu Han","doi":"10.1016/j.bpsgos.2025.100656","DOIUrl":"10.1016/j.bpsgos.2025.100656","url":null,"abstract":"<div><h3>Background</h3><div>Cumulative stress is a major risk factor for developing major depressive disorder (MDD), but not everyone experiencing chronic stress develops MDD. In those who do not, it is unclear at what point or by what mechanism a trajectory of stable resiliency emerges.</div></div><div><h3>Methods</h3><div>Utilizing a 10-day repeated social defeat stress (RSDS) model for MDD, we observed that a critical period between 7 and 10 daily defeats marks the phenotypical divergence of resilient from susceptible male mice. Cell-type selective electrophysiology, chemogenetics, optogenetics, and RNA quantification were used to investigate the nature of stress effects on neuroadaptation in the oval nucleus of the bed nucleus of the stria terminalis (BNSTov) required to determine resilience.</div></div><div><h3>Results</h3><div>In response to ongoing stress, corticotropin-releasing factor (CRF⁺, but not CRF⁻) neurons of the BNSTov displayed a sustained increased firing rate in resilient but not susceptible mice. This neurophysiological adaptation was self-sustaining, but only after 7 critical stress exposures, indicating that the process of developing resilience is dependent on stress history.</div></div><div><h3>Conclusions</h3><div>Our study reveals a novel process by which individuals may persist in the face of adversity by way of stress-provoked activation, not inhibition of a key CRF limbic region that establishes a pathway to resilience.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100656"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038037","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":"Moving Beyond Self-Report in Characterizing Drug Addiction: Using Drug-Biased Behavior to Predict Treatment Completion and Dropout in Heroin-Primary, Medication-Maintained Opioid Use Disorder","authors":"Natalie McClain ,&nbsp;Ahmet O. Ceceli ,&nbsp;Kathryn Drury ,&nbsp;Greg Kronberg ,&nbsp;Eric L. Garland ,&nbsp;Nelly Alia-Klein ,&nbsp;Rita Z. Goldstein","doi":"10.1016/j.bpsgos.2025.100667","DOIUrl":"10.1016/j.bpsgos.2025.100667","url":null,"abstract":"<div><h3>Background</h3><div>Drug addiction is accompanied by enhanced salience attributed to drug over nondrug cues. This bias can be objectively measured and is reliable but underutilized in informing clinical end points, where self-report measures are most commonly used, with limited success.</div></div><div><h3>Methods</h3><div>We investigated whether behavioral picture choice (laboratory-simulated measure of drug seeking) and verbal fluency (drug and nondrug words generated) revealed drug-biased processing in 59 individuals with opioid use disorder (iOUDs) compared with 29 healthy control (HC) individuals; assessed twice, we also inspected the test-retest reliability of these tools. All iOUDs were heroin primary, abstinent (160.58 ± 188.18 days), and stabilized on medication for OUD at an inpatient treatment facility at baseline. Then, we tested whether, compared with self-report measures, these drug-biased behavioral measures could better predict prospective outcome measures in the iOUDs, i.e., study treatment completion as further validated using dropout from inpatient treatment.</div></div><div><h3>Results</h3><div>Results revealed that the iOUDs exhibited higher drug choice (<em>p</em>s &lt; .036) and drug fluency (<em>p</em> = .008) compared with the HC individuals; task performance demonstrated the strong test-retest reliability of these measures. Controlling for cognitive demographics, the self-report drug-use severity and craving measures did not show significant associations with study treatment completion (|β| &lt; 0.47, <em>p</em>s &gt; .290), but drug-biased choice did (β = −0.75, <em>p</em> = .036; model comparison: Δ<em>R</em>² = 0.10, <em>p</em> = .027). Importantly, these results were validated using inpatient treatment dropout as the outcome (drug-biased choice: β = 0.81, <em>p</em> = .049; model comparison: Δ<em>R</em>² = 0.11, <em>p</em> = .035).</div></div><div><h3>Conclusions</h3><div>This study is the first to demonstrate reliable drug-biased choice and fluency in iOUDs. Compared with traditional self-reported drug-use and craving measures, the objective drug-biased cognitive behavioral measure was a significant predictor of treatment-related outcomes.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100667"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038039","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(26)00017-0","DOIUrl":"10.1016/S2667-1743(26)00017-0","url":null,"abstract":"","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100704"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147538137","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":"Rare Variants in Antisense Long Noncoding RNA–Protein-Coding Gene Overlap Regions Contribute to Obsessive-Compulsive Disorder","authors":"Seulgi Jung ,&nbsp;Madison Caballero ,&nbsp;Shelby Smout ,&nbsp;Behrang Mahjani","doi":"10.1016/j.bpsgos.2025.100683","DOIUrl":"10.1016/j.bpsgos.2025.100683","url":null,"abstract":"<div><h3>Background</h3><div>Obsessive-compulsive disorder (OCD) is a prevalent neuropsychiatric disorder with an incompletely understood genetic basis, limiting targeted therapeutic options. Although previous rare-variant studies have primarily focused on protein-coding genes, the contribution of rare regulatory noncoding variants remains largely unexplored.</div></div><div><h3>Methods</h3><div>We analyzed whole-genome sequencing data from 2561 OCD cases and 12,974 controls from the All of Us Research Program to investigate rare conserved variants within 992 genomic regions where antisense long noncoding RNAs (lncRNAs) overlap protein-coding genes, using both Fisher’s exact test and the Optimal Sequence Kernel Association Test for association testing.</div></div><div><h3>Results</h3><div>We identified significant enrichment of rare conserved variants in the <em>KNCN</em>/<em>MKNK1-AS1</em> overlap region in OCD cases (odds ratio = 5.1, false discovery rate &lt; .05). This enrichment was significant in overlapping regions of genes with low evolutionary constraint. Expression analysis revealed strong coexpression of <em>KNCN</em> and <em>MKNK1-AS1</em> specifically in striatal brain regions (nucleus accumbens: <em>r</em> = 0.83, putamen: <em>r</em> = 0.81, caudate: <em>r</em> = 0.79)—key components of circuits disrupted in OCD. Genes coexpressed with this regulatory pair were enriched for synaptic vesicle dynamics, calcium signaling, and established OCD risk genes from genome-wide association studies (false discovery rate &lt; .05).</div></div><div><h3>Conclusions</h3><div>These results highlight the importance of rare noncoding regulatory variation in OCD genetics. The association of <em>KNCN</em>/<em>MKNK1-AS1</em> variants with OCD suggests that antisense lncRNA–protein-coding overlap regions may contribute to disease susceptibility and represent potential therapeutic targets.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100683"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146168143","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":"Phenome-Wide Associations of Polygenic Scores for Schizophrenia and Major Depression in 100,000 Chinese Adults","authors":"Baihan Wang ,&nbsp;Sam Morris ,&nbsp;Hannah Fry ,&nbsp;Andri Iona ,&nbsp;Jonathan Clarke ,&nbsp;Kuang Lin ,&nbsp;Igor Pupko ,&nbsp;Christiana Kartsonaki ,&nbsp;Derrick A. Bennett ,&nbsp;Yiping Chen ,&nbsp;Huaidong Du ,&nbsp;Ling Yang ,&nbsp;Daniel Avery ,&nbsp;Dan Schmidt-Valle ,&nbsp;Shixian Feng ,&nbsp;Dianjianyi Sun ,&nbsp;Canqing Yu ,&nbsp;Jun Lv ,&nbsp;Pei Pei ,&nbsp;Junshi Chen ,&nbsp;Iona Y. Millwood","doi":"10.1016/j.bpsgos.2025.100681","DOIUrl":"10.1016/j.bpsgos.2025.100681","url":null,"abstract":"<div><h3>Background</h3><div>China faces significant mental health challenges, with unique associations between mental disorders and other traits observed in its population.</div></div><div><h3>Methods</h3><div>Based on summary statistics of existing genome-wide association studies in East Asian ancestry (EAS) and European ancestry (EUR) populations, we tested the associations of polygenic scores (PGSs) for schizophrenia (SCZ) and major depression (MD) with 254 phenotypes in 100,640 Chinese adults. We also conducted genetic correlation and Mendelian randomization analyses to assess the consistency of these associations across ancestries and infer causality.</div></div><div><h3>Results</h3><div>The PGSs predicted SCZ (<em>R</em>² = 2.63%–3.07%) and MD (<em>R</em>² = 0.21%–0.71%) and were associated with various sociodemographic, lifestyle, and physical factors. Interestingly, based on summary statistics in the EAS population, the schizophrenia PGS was inversely associated with smoking initiation, and the MD PGS was inversely associated with body mass index. Across populations, opposing genetic correlations were observed between smoking initiation and SCZ (inverse in the EAS population, positive in the EUR population) and between body mass index and MD (inverse in the EAS population, positive in the EUR population). Univariable Mendelian randomization supported the causality of these relationships in the EUR population, but multivariable analyses suggested that pleiotropic effects on other related traits (e.g., cannabis use, unhealthy lifestyle) might have influenced the associations.</div></div><div><h3>Conclusions</h3><div>Our study suggests the context specificity of relationships between mental disorders and other traits, highlighting a potential role of sociocultural factors.</div></div>","PeriodicalId":72373,"journal":{"name":"Biological psychiatry global open science","volume":"6 2","pages":"Article 100681"},"PeriodicalIF":3.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146215032","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}