Molecular Psychiatry最新文献

{"title":"Unraveling the multifaceted relationship between creativity and mental health with longitudinal analyses of genotyped twins.","authors":"Penghao Xia, Laura W Wesseldijk, Yi Lu, Sverker Sikström, Örjan de Manzano, Vivien Vach, Fredrik Ullén, Miriam A Mosing","doi":"10.1038/s41380-026-03925-5","DOIUrl":"https://doi.org/10.1038/s41380-026-03925-5","url":null,"abstract":"<p><p>Existing findings of creativity and mental health associations are inconsistent, partly due to heterogeneous assessment of creativity and mental health. Consequently, basic questions concerning the direction and domain specificity of these associations remain unanswered. This comprehensive study used data from 14 658 Swedish twins, including a genotyped subsample, and employed a range of genetically informed and longitudinal designs to examine the direction, nature, and underlying mechanisms of the creativity-mental health relationship. Creativity was assessed broadly, using different measures of artistic and scientific achievement, occupation, personality (openness), and psychometric creativity (divergent thinking). Mental health was measured using both self-report data and registry-based diagnoses. Higher artistic creativity, as indexed by artistic achievement and openness, was associated with worse mental health (e.g., psychosis proneness, major depressive disorder, and anxiety disorder). In contrast, measures of scientific creativity showed predominantly non-significant, or even negative, associations with mental health problems, particularly in the case of occupational creativity. Co-twin control and polygenic score analyses suggested that shared genetic factors played an important role in the observed associations, with the exception of a potential causal association between depressive symptoms and openness, which persisted even in the longitudinal co-twin control model. Genetic correlations further showed shared underlying genetic influences. In summary, our findings offer novel evidence for a complex, bidirectional, and genetically influenced association between artistic creativity and mental health, helping to clarify mixed results in the prior literature.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.4,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137585","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":"Correction: Digital mood phenotyping predicts short- and long-term suicidal ideation across a two-year timescale","authors":"Chang Lei,Xuan Geng,Zhijun Wu,Xiaoxiao He,Shuohan Yang,Weijian Wu,Kunxu Liu,Diyang Qu,Yingjun Xi,Jing An,Runsen Chen","doi":"10.1038/s41380-026-03808-9","DOIUrl":"https://doi.org/10.1038/s41380-026-03808-9","url":null,"abstract":"","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"8 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088954","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":"Prenatal stress reprograms placental signaling and opposes maternal immune activation effects in the fetal brain","authors":"Branden G. Verosky,Helen J. Chen,Jessica L. Anderson,Therese A. Rajasekera,Maya Neidhart,Suhanna Halaharvi,Brett L. Worly,Andy J. Fischer,Tamar L. Gur","doi":"10.1038/s41380-026-03914-8","DOIUrl":"https://doi.org/10.1038/s41380-026-03914-8","url":null,"abstract":"Abstract Prenatal psychosocial stress and maternal immune activation (MIA) increase risk for overlapping offspring psychiatric disorders, but whether they influence fetal neurodevelopment through shared or distinct mechanisms is unclear. Positioned at the interface of maternal and fetal physiology, the placenta has a critical role in regulating fetal brain development. Here, we combine mouse placental single-cell RNA sequencing, transcriptomics of matched placentas and fetal brains, maternal cytokine profiling, and human placental RNA-seq to dissect this axis. In mice, chronic stress suppressed interferon signaling across placental immune cells and downregulated oxidative phosphorylation pathway expression in trophoblasts. Stressed dams also mounted a blunted type I interferon response to poly(I:C), resulting in attenuated placental antiviral signaling. Weighted gene co-expression analysis of fetal brains revealed that prenatal stress and MIA regulate overlapping DNA repair, synaptic, and translational networks in opposite directions, with stress promoting signatures of premature maturation and MIA driving replication stress. In human placentas, higher perceived stress was associated with chromatin-regulatory, RNA-metabolic, and extracellular-matrix modules that mirrored the murine stress signature. These findings identify a conserved placental stress-associated transcriptional program and suggest that stress and MIA affect shared neurodevelopmental pathways in opposing directions.","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"6 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088955","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":"Executive functions as a transdiagnostic endophenotype in developmental psychopathology","authors":"Eleanor K. Braithwaite,Jennifer C. Fielder,Nikolaus Steinbeis","doi":"10.1038/s41380-026-03916-6","DOIUrl":"https://doi.org/10.1038/s41380-026-03916-6","url":null,"abstract":"Abstract The majority of mental health conditions emerges before adulthood, with prevalence increasing especially during childhood and adolescence. Coupled with high comorbidity between disorders, there is an urgent need to identify transdiagnostic mechanisms that underpin both risk and resilience to developmental psychopathology. Here we propose executive functions (EFs), a set of cognitive processes relevant for goal-directed control of thought and actions, as a promising candidate for such a mechanism. We review evidence that EF development is shaped by both genetic and environmental factors and relies on protracted maturation of neural networks, particularly frontoparietal and cingulo-opercular systems. Disruptions in these systems are associated with elevated risk for internalising and externalising disorders. We therefore propose EFs as a cognitive endophenotype of developmental psychopathology—heritable, measurable, and lying on the pathway from gene to disorder. We review evidence showing that impaired EF is a shared feature across psychiatric conditions and predictive of future symptomatology, supporting its transdiagnostic relevance. We also propose a mechanistic refinement of the EF construct, moving beyond capacity-based interpretations to a model in which EF performance reflects dynamic and contextually informed cost-benefit computations. Disruptions in reward and effort processing—manifesting as anhedonia and apathy—are common across mental health conditions and may compromise EF performance by altering these computations. This integrative perspective helps explain the limited efficacy of traditional EF training interventions on improving mental health symptoms and underscores the importance of motivational and contextual factors. We conclude by outlining a future research agenda focussed on disentangling the specific subprocesses underpinning EFs and their mechanistic links to developmental psychopathology. Recognising EFs as a transdiagnostic cognitive endophenotype governed by rational control processes opens new avenues for precise, developmentally informed, and targeted interventions in youth mental health.","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"1 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088957","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":"Correction: Altered function of peripheral organ systems in first-episode drug naïve mental illnesses: a systematic review and meta-analysis","authors":"Jetro E. Ang,Yangqi Xu,Vanessa Cropley,Andrew Zalesky,Ye Ella Tian","doi":"10.1038/s41380-026-03924-6","DOIUrl":"https://doi.org/10.1038/s41380-026-03924-6","url":null,"abstract":"","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"218 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088956","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":"Acetaminophen produces limited molecular and functional effects in human cortical organoids","authors":"Luca Trovò, George Kucera, Gimena Gomez, Janaina Sena de Souza, Alysson R. Muotri, Lilia M. Iakoucheva","doi":"10.1038/s41380-026-03920-w","DOIUrl":"https://doi.org/10.1038/s41380-026-03920-w","url":null,"abstract":"Acetaminophen (APAP) is the most widely used analgesic during pregnancy, yet its effects on prenatal human brain development remain incompletely understood. Epidemiological studies have reported inconsistent associations between prenatal APAP exposure and later neurodevelopmental outcomes, underscoring the need for mechanistic evaluation in human-relevant developmental models. Here, we examined how APAP influences early cortical development using induced pluripotent stem cell-derived cortical organoids (COs) generated from six independent lines. Organoids were exposed to physiologically relevant APAP concentrations (25, 50, and 100 μM) for 5 days beginning at day 21 of differentiation, corresponding to late first-trimester cortical development. We assessed organoid growth, apoptosis, differentiation, synaptic maturation, transcriptomic profiles using bulk and single-nucleus RNA sequencing (snRNA-seq), and functional network activity using multielectrode array recordings up to 4 months. APAP exposure did not affect organoid size, cytoarchitecture, or viability. Neuronal and progenitor cell proportions, as well as synaptic puncta density were unchanged. Bulk RNA-seq revealed subtle transcriptional changes only at the highest dose (16 differentially expressed genes at 100 μM), enriched for neurodevelopmental pathways. In contrast, snRNA-seq at 3 months revealed no changes in cell type composition or gene expression. Consistent with the limited molecular changes observed, electrophysiological measures including firing rate, burst frequency, and network synchrony, showed no significant differences from controls. Together, these results indicate that direct exposure to parent APAP at the concentrations tested produces minimal molecular perturbations. These findings reflect responses to parent acetaminophen in vitro and do not exclude metabolite-mediated or systemic effects in vivo.","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087817","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":"Association between polygenic liability to depression and lifetime depression in at-risk adolescents","authors":"Enda M. Byrne, Nathan A. Gillespie, Jake M. Najman, Anjali K. Henders, Brittany L. Mitchell, Dominic Dwyer, Simon Hartmann, Blake S. Cavve, G. Paul Amminger, Scott Clark, Caroline Gao, Ashleigh Lin, Lianne Schmaal, Andrew Thompson, Stephen J. Wood, J.T.W Wigman, Alison R. Yung, Sarah E. Medland, Jacob J. Crouse, Jan Scott, James G. Scott, Gail M. Williams, Barnaby Nelson, Nicholas G. Martin, Ian B. Hickie, Naomi R. Wray, Christel M. Middeldorp","doi":"10.1038/s41380-026-03917-5","DOIUrl":"https://doi.org/10.1038/s41380-026-03917-5","url":null,"abstract":"Internalising symptoms including depression, anxiety and somatic symptoms in adolescence are common. They can be transient, but they can also persist and progress to major depressive disorder (MDD) Polygenic risk scores for major depression (MD-PGS) may help identify which symptomatic adolescents are at greatest risk of later disorder. In a mega-analysis of two longitudinal population-based cohorts from Brisbane, Australia, we investigated whether polygenic liability to depression improves risk stratification among adolescents with elevated internalising symptoms. Internalising symptoms were assessed at age 14, lifetime MDD was assessed in young adulthood using the Composite International Diagnostic Interview, and MD-PGS were generated using summary statistics from the latest Psychiatric Genomics Consortium major depression genome-wide association study, excluding Australian cohorts. Analyses focused on comparisons between individuals in the top decile of risk and those in the remaining 90% of each cohort. A total of 302 cases with lifetime MDD and 1693 controls were included. Compared with adolescents outside the highest decile of internalising symptoms, those in the top decile at age 14 had a more than two-fold increased odds of lifetime MDD (OR = 2.56, 95% CI 1.92–3.49, p = 5.4 × 10-10). Individuals in the top decile of MD-PGS also showed increased odds of lifetime MDD compared with the remaining 90% (OR = 3.45, 95% CI 2.53–4.71, p = 4.4 × 10−¹⁵). Adolescents who were simultaneously in the top decile of both internalising symptoms and MD-PGS had an approximately eight-fold increased odds of lifetime MDD compared with individuals outside the top decile for both risk factors (OR = 8.58, 95% CI 4.04–18.26, p = 1.2 × 10−⁵). These findings indicate that polygenic risk scores for depression may have particular clinical utility for stratifying risk among adolescents already presenting with elevated internalising symptoms, identifying a subgroup at very high risk for later major depressive disorder.","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"3 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087820","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":"Psychedelics and disorders of consciousness: a new frontier in neurotherapeutics","authors":"Xiubo Du,Feiyuan Peng,Xiaohui Wang","doi":"10.1038/s41380-026-03918-4","DOIUrl":"https://doi.org/10.1038/s41380-026-03918-4","url":null,"abstract":"","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"295 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149092038","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":"Reframing stress adaptation as a dynamic system failure along a threat-response continuum: towards a phase-specific, mechanism-driven framework","authors":"Dong’e Huang, Munan Lin, Junqing Dong","doi":"10.1038/s41380-026-03888-7","DOIUrl":"https://doi.org/10.1038/s41380-026-03888-7","url":null,"abstract":"","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"12 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087818","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":"Investigating the associations between neurodevelopmental and psychiatric genetic liability and adverse social and functional outcomes across childhood, adolescence and young-adulthood","authors":"Beatrice Fury, Charlotte Dennison, Lucy Riglin, Amy Shakeshaft","doi":"10.1038/s41380-026-03903-x","DOIUrl":"https://doi.org/10.1038/s41380-026-03903-x","url":null,"abstract":"Neurodevelopmental and psychiatric conditions often originate in youth and can lead to adverse social and functional outcomes. It is unclear whether these associations are driven by genetic liability to these conditions, with possible developmental differences. We examined multivariable associations between polygenic scores (PGS) for attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), schizophrenia, bipolar disorder, depression, anxiety and three outcomes: peer problems, educational attainment/employment and suicidality, in childhood, adolescence and young-adulthood. Data were analysed from the Avon Longitudinal Study of Parents and Children; outcomes at ages 10–13, 16 and 24–25 years. ADHD PGS was associated with peer problems (OR = 1.13, p = 0.020; OR = 1.21, p < 0.0001; OR = 1.14, p = 0.010) and lower educational attainment/employment in childhood, adolescence and young-adulthood(OR = 1.40, p < 0.0001; OR = 1.62, p < 0.0001; OR = 1.29, p = 0.005 respectively) and suicidality in childhood (OR = 1.13, p = 0.030). ASD PGS was associated with peer problems and suicidality in childhood (OR = 1.24, p < 0.0001; OR = 1.24, p = <0.0001) and greater educational attainment in childhood and adolescence (OR = 0.88, p = 0.004; OR = 0.77, p = 0.007). Depression PGS was associated with peer problems in childhood and young-adulthood (OR = 1.18, p = 0.003; OR = 1.21, p < 0.0001), and poorer educational attainment/employment and suicidality in adolescence (OR = 1.39, p = 0.004; OR = 1.28, p < 0.0001) and young-adulthood (OR = 1.26, p = 0.017; OR = 1.42, p < 0.0001). We did not find strong evidence of associations for schizophrenia, bipolar disorder or anxiety PGS. These findings suggest that genetic liability to neurodevelopmental and psychiatric conditions are associated with a range of social/functional outcomes, although the strength and direction of association vary by PGS, outcome and development stage. This highlights the importance of examining genetic liability to multiple conditions simultaneously and of a developmental perspective.","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":"18 1","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149087819","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}