Schizophrenia Bulletin最新文献

{"title":"Fetal Head Growth and Head Circumference at Birth in Children of Women with Psychotic Disorders and Population-Based Controls","authors":"Lisanne A E M van Houtum, Dogukan Koc, Sterna A Grundeman, Hans J Duvekot, Hanan El Marroun, Neeltje E M van Haren, Hilmar H Bijma","doi":"10.1093/schbul/sbaf171","DOIUrl":"https://doi.org/10.1093/schbul/sbaf171","url":null,"abstract":"Background Children of parents with psychotic disorders have a ˃50% increased risk to develop mental health problems, and over 30% have developed severe mental illness by early adulthood. Aberrant brain development may underly this familial risk. We aimed to investigate differences in brain development, reflected in fetal head circumference (HC) growth trajectories and HC at birth, between children of women with psychotic disorders and population-based controls. Study Design We collected fetal ultrasonography assessments at 20, 30, and 36 weeks of gestational age (GA) from medical records of N = 140 pregnant women having a psychotic disorder diagnosis and their N = 168 children. In the Generation R study, ultrasonography assessments were performed in the first, second, and/or third trimester in N = 8605 pregnant women and their children. In both groups, HC at birth was measured with measuring tape. Study Results Using generalized additive mixed modeling, we observed decreased non-linear fetal HC growth for offspring of women with psychotic disorders vs. controls from 30.7 weeks GA onwards. At birth, no significant difference was observed (b = 0.22, 95% CI [–0.133 to 0.573]), although offspring exposed to maternal psychosis showed more obstetric complications and suboptimal birth outcomes, including lower birthweight (b = –136.1, 95% CI [–229.0 to –43.2]). Conclusions This study showed decreased fetal head growth during the third trimester and lower birthweight in children of women with psychotic disorders. Together, these findings highlight potential relevance of altered fetal head growth for later neurodevelopmental outcomes and provide directions for possible underlying mechanisms of risk transmission in psychosis.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"4 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183190","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 Responses to Reward and Psychosis Dimensions","authors":"Brady D Nelson, Marcela E Gallardo, Katherine G Jonas, Evelyn J Bromet, Roman Kotov","doi":"10.1093/schbul/sbaf165","DOIUrl":"https://doi.org/10.1093/schbul/sbaf165","url":null,"abstract":"Background and Hypothesis Deficits in motivational drive, reinforcement learning, and reward prediction have been implicated in psychotic disorders. Electroencephalography (EEG) measures of these processes have demonstrated inconsistent relationships with psychotic disorders. The present study addressed key limitations in the literature and examined the association between multiple EEG neural responses to reward and different psychosis dimensions. Study Design The sample included 362 adults (age M = 49.87, 42.3% female): 169 with a history of hospitalization for a psychotic disorder and 193 demographically matched with no history of a psychotic disorder. Participants completed a monetary guessing task, and we measured the time-domain reward positivity (RewP) as well as time-frequency delta activity to win and theta activity to loss. Participants also completed clinical interviews, questionnaires, and neuropsychological measures. Study Results Categorical analyses indicated no group differences in the RewP, but participants with schizophrenia or schizoaffective disorder had more blunted delta activity to win and theta activity to loss. Dimensional analyses indicated more blunted RewP, delta activity to win, and theta activity to loss were associated with greater psychosis dimension scores. More blunted delta activity to win was also associated with greater lower-order detachment and higher-order general psychopathology dimension scores. Executive functions mediated the relationship between both delta and theta activity and the psychosis dimension. Conclusions Blunted EEG time-domain and time-frequency neural responses to reward are associated with dimensional representations of psychosis. The study also highlights the importance of cognitive deficits when examining the neural response to reward and psychosis.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"70 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183094","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":"Large-Scale Public Stigma Reduction Toward Individuals With Psychosis Using Brief Videos: A Secondary Data Analysis","authors":"Samantha E Jankowski, Chana T Fisch, Philip Yanos, Lisa B Dixon, Doron Amsalem","doi":"10.1093/schbul/sbaf168","DOIUrl":"https://doi.org/10.1093/schbul/sbaf168","url":null,"abstract":"Background Stigma toward individuals living with psychosis impacts treatment seeking and outcomes among youth. Brief social contact-based video interventions (<3 min long) can be disseminated via social media to reduce stigma. However, it is unclear how these videos impact distinct components of stigma (negative attitudes and behavioral intentions) and whether matching on demographic characteristics (race and gender) between protagonist and viewer bolsters effects. Study Design and Hypothesis We explored these questions in a secondary data analysis of 6 prior randomized controlled trials varying in presenter characteristics (race, gender, lived experience, actor) and video modality (selfie vs traditional style) in 6946 United States youth, ages 18-30, recruited via Prolific. It was hypothesized that our results would replicate previous findings on efficacy of brief videos on reducing stigma and that there would be a significant impact on cognitive and behavioral subdomains and a matching effect for gender and race. Study Results Results replicated prior findings that video interventions were effective at reducing stigma across 5 domains (social distance, stereotyping, separateness, social restriction, and perceived recovery) and contributed to an overall shift in stigmatizing attitudes and behavioral intentions at post-intervention and 30-day follow-up. Videos that matched viewers’ gender or race had significantly stronger stigma-reduction effects on certain domains, though effect sizes were small. Study Conclusions Results highlight that brief, easy-to-disseminate videos can effectively change stigmatizing perceptions and behavioral intentions toward individuals with psychosis. Future studies should explore how behavioral intentions translate to action and the impact of matching between presenters and participants.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"95 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182986","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":"Psychosocial Interventions for Older Adults With Severe Mental Illness: A Systematic Scoping Review and Meta-analysis.","authors":"Macarena Sánchez-Izquierdo, Ignacio Echegoyen, Ellen Lee, Vanesa Peinado, Francisco López-Arroyo, Rocío Caballero","doi":"10.1093/schbul/sbaf169","DOIUrl":"https://doi.org/10.1093/schbul/sbaf169","url":null,"abstract":"<p><strong>Background: </strong>Older adults with severe mental illness (SMI) experience complex rehabilitative needs that are often neglected in clinical and research settings. Psychosocial interventions are key to supporting recovery; however, evidence specific to this population remains fragmented. This scoping review and meta-analysis aims to synthesize available research on psychosocial interventions designed for older adults with SMI and evaluate their effectiveness.</p><p><strong>Study design: </strong>Following the Arksey and O'Malley framework and PRISMA-ScR guidelines, we conducted a comprehensive search across PubMed, PsycINFO, and Scopus for studies published between 2000 and 2023. Eligibility was based on the PICO framework, focusing on adults aged ≥ 50 with SMI. Data were extracted and analyzed using descriptive synthesis and meta-analytic techniques.</p><p><strong>Study results: </strong>Sixteen studies met the inclusion criteria, encompassing 884 participants. Interventions primarily targeted clinical recovery, with limited focus on aspects of personal recovery. Meta-analysis indicated a moderate overall effect size (ES = 0.366, P < .0001) with low heterogeneity (I2 = 18.81%). Quality assessment revealed that 62.5% of studies had medium to high risk of bias.</p><p><strong>Conclusions: </strong>While psychosocial interventions show promise in improving clinical outcomes for older adults with SMI, there is a significant gap in addressing personal recovery dimensions. Future research should emphasize holistic, long-term interventions to enhance both clinical and personal recoveries.</p>","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150437","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":"Cortical Transcriptomic Profiling Reveals Cellular and Mitochondrial Adaptive Stress Signatures That Differ Between Schizophrenia and Bipolar Disorder.","authors":"Jill R Glausier, John F Enwright, David A Lewis","doi":"10.1093/schbul/sbaf147","DOIUrl":"https://doi.org/10.1093/schbul/sbaf147","url":null,"abstract":"<p><strong>Background and hypothesis: </strong>Identifying the nature of mitochondrial perturbations in brain regions dysfunctional in schizophrenia (SZ) and bipolar disorder (BP) is essential to decipher their disease processes. Employing \"threshold-free\" analytical approaches that evaluate patterns of gene expression differences and functional pathway enrichment can inform the shared and distinct aspects of SZ and BP disease processes. We hypothesized that transcriptomic signatures will be concordant, selectively within brain regions affected in both disorders.</p><p><strong>Study design: </strong>SZ and BP transcriptomic signatures were evaluated in the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC), 2 regions that mediate different functions and are differentially affected by the disorders. Rank-rank hypergeometric overlap and gene-set enrichment analysis, 2 complementary analytical approaches that incorporate multiple quantitative measures to identify patterns of gene expression differences, were applied for transcriptome-wide and Gene Ontology \"Mitochondria\" (GO_Mito) analysis.</p><p><strong>Study results: </strong>SZ disease effects were highly concordant across the DLPFC and ACC; findings reflected lower oxidative phosphorylation (OXPHOS) and greater translational repression. BP disease effects were weakly concordant across the DLPFC and ACC. Cross-diagnostic comparisons revealed transcriptomic concordance predominately within the ACC, especially for OXPHOS genes.</p><p><strong>Conclusions: </strong>The SZ and BP disease effects on biological processes, particularly OXPHOS, are similar within the ACC but not the DLPFC. The overall constellation of findings in SZ was highly consistent with protective cellular responses that re-establish homeostasis after pathogenic insults. Together, these findings provide key insight into the potential substrates of DLPFC and ACC dysfunction that is associated with cognitive and affective dysregulation, respectively, in SZ and BP.</p>","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145131894","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":"Sex-dependent Schizophrenia and Drug Reward Behavioral Phenotypes in Metabotropic Glutamate 5 Receptor Heterozygous and Homozygous Mice.","authors":"Rossana Rosa Porto, Fabian Kreilaus, Anthony J Hannan, Rose Chesworth, Tim Karl","doi":"10.1093/schbul/sbaf161","DOIUrl":"https://doi.org/10.1093/schbul/sbaf161","url":null,"abstract":"<p><strong>Background and hypothesis: </strong>The metabotropic glutamate 5 (mGlu5) receptor is a potential therapeutic target for psychiatric disorders, including schizophrenia and substance use disorders. Indeed, mGlu5 is expressed in forebrain regions (eg, striatum, prefrontal cortex), and mGlu5 modulates N-methyl-D-aspartate receptor function and second messenger signaling. Also, male mice lacking mGlu5 display schizophrenia-like and substance use-relevant behaviors. However, there are limited investigations of sex differences or gene-dose effects in this model.</p><p><strong>Study designs: </strong>We evaluated schizophrenia-relevant and cocaine reward-relevant behaviors in adult male and female mice with heterozygous (mGlu5 HET) and homozygous (mGlu5 HOMO) mGlu5 deletion and their wildtype-like (WT) littermates. We assessed locomotion and exploration, anxiety, sensorimotor gating, novel object recognition, fear conditioning, social interaction, cocaine sensitization, and cocaine-conditioned place preference. We also examined fear memory generalization.</p><p><strong>Study results: </strong>mGlu5 HOMO mice of both sexes showed hyperlocomotion and anxiolytic-like behavior in the open field, as well as enhanced cocaine sensitization and persistent cocaine place preference. When tested for memory generalization, mGlu5 HOMO mice exhibited greater freezing to a novel context, suggesting overgeneralization of fear in these mice. mGlu5 HOMO females showed reduced sensorimotor gating. mGlu5 HET mice of both sexes showed a largely similar phenotype to sex-matched WT controls.</p><p><strong>Conclusions: </strong>Our data demonstrate schizophrenia- and drug use-relevant phenotypes in mGlu5 HOMO mice, some of which are sex-dependent. These phenotypes do not occur in mGlu5 HET males and females. We also show for the first time an overgeneralization phenotype in mGlu5 HOMO mice, which may be related to poor contextual discrimination.</p>","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145114053","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":"Age of Onset, Brain Controllability, and Working Memory Performance in First-Episode Schizophrenia","authors":"Feiwen Wang, Zhening Liu, Jun Yang, Peng Cheng, Wenjian Tan, Danqing Huang, Xiawei Liu, Maoxing Zhong, Jie Yang, Lena Palaniyappan","doi":"10.1093/schbul/sbaf156","DOIUrl":"https://doi.org/10.1093/schbul/sbaf156","url":null,"abstract":"Background and Hypothesis The onset-age of schizophrenia introduces considerable heterogeneity in cognitive functions such as working memory (WM) among patients. One of the key properties of the brain that varies with age-related development is the network-level controllability of brain state transitions. We tested the effect of onset-age on brain controllability to evaluate its impact on WM deficits in schizophrenia. Study Design We examined the average and modal controllability of the brain connectome in 85 first-episode early-onset schizophrenia (EOS), 62 younger healthy controls (yHC), 71 first-episode adult-onset schizophrenia (AOS), and 85 older healthy controls (oHC) during N-back tasks. We first detected the regions with illness and onset-age interaction in a whole-brain search, and then conducted a correlation analysis with WM performance and clinical characteristics, followed by an out-of-sample gene annotation analysis. Study Results We detected the illness*onset-age interaction in the sensorimotor network, auditory network, and subcortical network for average controllability and the default mode network, visual network, and salience network for modal controllability (p-fdr &amp;lt; 0.05). The interaction effects in the visual and subcortical networks primarily resulted from the AOS vs. oHC differences; the effects in the default mode network resulted from EOS vs. yHC differences. We observed no significant correlation between controllability with cognitive performance or clinical characteristics. The affected regions had preferential expression of genes relevant to synaptic signaling and neurodegenerative processes (p-fdr &amp;lt; 0.05). Conclusion Onset-age introduces considerable heterogeneity in the controllability over brain state transition during WM tasks among patients with schizophrenia.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"16 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089673","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 Mini-CAARMS: Development and Validation of a Short Version of the Comprehensive Assessment of AT Risk Mental States to Facilitate Preventive Psychiatry","authors":"Alberto Stefana, Dominic Oliver, Andrés Estradé, Matilda Azis, Stefano Damiani, Laura Fusar-Poli, Natascia Brondino, Umberto Provenzani, Ilaria Bonoldi, Peter J Uhlhaas, Paolo Fusar-Poli","doi":"10.1093/schbul/sbaf146","DOIUrl":"https://doi.org/10.1093/schbul/sbaf146","url":null,"abstract":"Background and Hypothesis Accurate detection of individuals at risk for psychosis with established psychometric instruments such as the Comprehensive Assessment of At-Risk Mental States (CAARMS/2006) is crucial to implement effective preventive strategies. However, the CAARMS/2006’s scalability is limited by its lengthy administration. This study developed and validated a shorter CAARMS/2006 version: the mini-CAARMS. Study Design A total of 490 participants (mean age 23.8 ± 5 years) underwent the full CAARMS/2006 interview (60 items, all individually scored). The development and validation of the mini-CAARMS employed advanced statistical methods: regularized logistic regression with a LASSO penalty within a nested cross-validation framework to retain core items; Cohen’s κ, Harrell’s C index, sensitivity, specificity, balanced accuracy, positive (PPV) and negative (NPV) predictive values to assess performance; Monte Carlo simulations to assess the 2-year prognostic accuracy for predicting psychosis onset. A sensitivity analysis developed and validated an ultra-mini-CAARMS. Study Results The mini-CAARMS retained only 23 items and demonstrated excellent accuracy compared to the full version: Cohen’s κ 0.90; Harrell’s C index 0.93, sensitivity 95.6%, specificity 100%, balanced accuracy 97.8%, PPV 100%, and NPV 86.3%. The prognostic sensitivity and specificity of the mini-CAARMS were 82.2% and 55.1%, respectively. Sensitivity analyses further developed and validated an ultra-mini-CAARMS (based on 12 items only), which achieved comparable performance, with κ 0.90, C index 0.91, sensitivity 94.4%, balanced accuracy 97.2%, PPV 100%, NPV 82.2%, and prognostic sensitivity and specificity 81.2% and 55.1%, respectively. Conclusions The mini-CAARMS maintains high accuracy while substantially reducing administration time, and it could facilitate scalability of preventive psychiatry in low-resource settings.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"1 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089672","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 Significance of Psychotic Experiences in Preadolescent Children with Non-Psychotic Mental Disorders—The Danish High Risk and Resilience Study, VIA 11","authors":"Maja Gregersen, Sinnika Birkehøj Rohd, Anne Søndergaard, Julie Marie Brandt, Jens Richardt Møllegaard Jepsen, Lotte Veddum, Christina Bruun Knudsen, Anna Krogh Andreassen, Carsten Hjorthøj, Mette Falkenberg Krantz, Aja Neergaard Greve, Ole Mors, Merete Nordentoft, Nicoline Hemager, Anne Amalie Elgaard Thorup","doi":"10.1093/schbul/sbaf164","DOIUrl":"https://doi.org/10.1093/schbul/sbaf164","url":null,"abstract":"Background and Hypothesis: Psychotic experiences (PE) are associated with higher severity of other psychopathology in adults and adolescents with non-psychotic mental disorders. Knowledge on the clinical significance of PE in children with non-psychotic mental disorders, which may help improve early identification of need for treatment, is sparse. Study Design: In this cross-sectional study, preadolescent children (n = 157, mean age 12.0, SD 0.2, range 11.1-12.7 years) at familial high-risk of schizophrenia (n = 78) or bipolar disorder (n = 40) and population-based controls (n = 39) with non-psychotic Axis I mental disorders during middle childhood were assessed for PE, dimensional psychopathology, multimorbidity, global functioning, and impact of psychopathology. Study Results: Children with PE had higher scores on total (Cohen’s d 0.40, P = .02) and internalizing dimensional symptoms (Cohen’s d 0.42, P = .02) and higher rates of multimorbidity, ie, meeting criteria for more than one mental disorder (OR 2.2, P = .04), than those without PE after accounting for familial risk. Children with PE had higher rates of self-reported impact of psychopathology after accounting for number of concurrent mental disorders and familial risk (OR 2.5, P = .01). The levels of externalizing symptoms and global functioning were not significantly different in those with and without PE. Conclusions: Presence of PE marks increased severity of concurrent non-psychotic psychopathology including more self-perceived impact of psychopathology in preadolescent children with mental disorders. PE could indicate a higher need for treatment and should be routinely assessed in child and adolescent mental health services.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"22 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089721","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":"Mendelian-Randomization Study Reveals Causal Relationships Between Blood Metabolites and Psychiatric Disorders","authors":"Changgai Mu, Xinglun Dang, Yonggui Yuan, Xiong-Jian Luo, Zhaowei Teng","doi":"10.1093/schbul/sbaf154","DOIUrl":"https://doi.org/10.1093/schbul/sbaf154","url":null,"abstract":"Background and Hypothesis Metabolic dysregulation has been widely observed in psychiatric disorders. However, the causal relationships between metabolites and psychiatric disorders remain largely unknown. Study Design Here, we conducted bidirectional Mendelian randomization (MR) analyses to systematically investigate causal relationships between 8 psychiatric disorders (including attention deficit hyperactivity disorder (ADHD), anorexia nervosa (AN), anxiety, bipolar disorder (BIP), depression, posttraumatic stress disorder (PTSD), insomnia, and schizophrenia (SCZ)) and 1139 blood metabolites (including 823 metabolite levels and 316 metabolite ratios). Study Results In forward MR, we identified 34, 21, 56, and 1 metabolites that are associated with BIP, SCZ, depression, and PTSD, respectively. Notably, several metabolites are associated with the risk of multiple psychiatric disorders. For instance, N2,N2-dimethylguanosine, 1,2-dipalmitoyl-gpc (16:0/16:0), and phosphatidylcholine acyl-alkyl C38:4 were negatively associated with the risk of SCZ and BIP. In reverse MR analyses, we explored the causal effects of psychiatric disorders on metabolites, and found that blood metabolites are also influenced by psychiatric disorders. For example, depression significantly affected 21 metabolite levels, including positively associated with 21-hydroxypregnenolone disulfate, and negatively associated with carotenoid. Conclusions Our findings not only uncover the causal relationships between metabolites and psychiatric disorders, but also provide potential therapeutic targets for the prevention and treatment of these psychiatric disorders.","PeriodicalId":21530,"journal":{"name":"Schizophrenia Bulletin","volume":"162 1","pages":""},"PeriodicalIF":6.6,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089720","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}