Molecular Psychiatry最新文献

{"title":"Posttranslational regulation of CREB-binding protein expression by F-box leucine-rich repeat-containing protein 19 and ubiquitin-specific peptidase 14 in the paraventricular nucleus participates in chronic stress-induced symptomatology via the modulation of the hypothalamic‒pituitary‒adrenal axis.","authors":"Wei-Jia Chen, Bao-Lun Zhu, Wei-Yu Li, Tian-Shun Shi, He-Yan Zhao, Cheng-Niu Wang, Xiao-Ling Zhang, Wei Guan, Jun-Jie Qian, Feng Zhang, Fei-Yang Jin, Jia-Yi Shen, Bo Jiang","doi":"10.1038/s41380-025-03293-6","DOIUrl":"https://doi.org/10.1038/s41380-025-03293-6","url":null,"abstract":"<p><p>The precise molecular mechanism by which chronic stress promotes the overexpression of corticotropin-releasing hormone (CRH) in the paraventricular nucleus (PVN) remains incompletely understood. Previous studies have revealed that cAMP-response element binding (CREB)-binding protein (CBP) directly participates in the regulation of CRH expression. The ubiquitination/degradation and deubiquitination/stabilization of CBP are regulated by F-box leucine-rich repeat-containing protein 19 (FBXL19) and ubiquitin-specific peptidase 14 (USP14), respectively. We hypothesized that the FBXL19-USP14-CBP system in the PVN might contribute to chronic stress-induced CRH release, and various methods were employed in this study. Our results revealed that both chronic social defeat stress (CSDS) and chronic unpredictable mild stress (CUMS) induced significant changes in the FBXL19-USP14-CBP system in the PVN of mice. Genetic knockdown of FBXL19, genetic overexpression of USP14/CBP, and stereotactic infusion of TAT-USP14 in the PVN all simulated chronic stress, inducing a similar symptomatology in naïve mice, and this effect was mediated by increased CRH biosynthesis, which required both the CBP‒CREB interaction and the acetyltransferase activity of CBP. In contrast, genetic overexpression of FBXL19 and genetic knockdown of USP14/CBP in the PVN reversed chronic stress-induced symptomatology in mice. Similarly, stereotactic infusion of TAT-FBXL19 into the PVN and intraperitoneal injection of IU1 also reversed chronic stress-induced symptomatology in mice. In addition, genetic knockout of USP14 and FBXL19 prevented and aggravated chronic stress-induced symptomatology in mice, respectively. Collectively, FBXL19, USP14, and CBP in PVN neurons correlate with chronic stress, and they could be viable targets for treating chronic stress-related neuropsychiatric disorders such as depression.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200391","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":"DNA hypomethylation at specific CG-sites within TRAK1 is linked to the neurocognitive profile in Klinefelter syndrome.","authors":"Helene B L Tallaksen, Emma B Hasselholm, Joel B Berletch, Gala N Filippova, Xinxian Deng, Daniel L Van Dyke, James W MacDonald, Theo K Bammler, Simon Chang, Cecilie D R Buskbjerg, Claus H Gravholt, Christine M Disteche, Jesper Just, Anne Skakkebæk","doi":"10.1038/s41380-025-03254-z","DOIUrl":"https://doi.org/10.1038/s41380-025-03254-z","url":null,"abstract":"<p><p>Klinefelter syndrome (47,XXY; KS) impacts neurodevelopment. Furthermore, KS is associated with widespread alterations in the epigenome and transcriptome. Whether these epigenetic and transcriptomic alterations can be linked to the neurocognitive phenotype remains to be elucidated. We performed a comprehensive, integrative analysis of the neurocognitive profile and the methylome in blood from males with KS (n = 65) and male controls (n = 63) (Cohort 1). The results were validated in a second cohort of males with KS (n = 22) and male controls (n = 16) in which transcriptome data was also available (Cohort 2). The findings were further validated in neural precursor cells derived from human induced pluripotent stem cells from 47,XXY (n = 3) and 46,XY (n = 3) amniotic cells. In cohort 1, we identified five CG-sites within the TRAK1 gene which were hypomethylated in males with KS compared to male controls. TRAK1 hypomethylation was positively correlated with several neurocognitive variables among males with KS. In cohort 2, we identified a similar methylation pattern and demonstrated that the methylation levels at the five CG-sites were correlated with a high expression level of a specific short TRAK1 transcript (ENST00000341421.7). Neural precursor cells (NPCs) established from 47,XXY amniotic cells also exhibited hypomethylation at the five CG-sites and strong upregulation of ENST00000341421.7 compared to NPCs established from 46,XY amniotic cells. In conclusion, we demonstrate that the DNA methylation level at specific CG-sites within TRAK1, a gene highly expressed in the brain, is correlated with the neurocognitive phenotype of KS, implying a possible epigenetic underpinning for the observed neurocognitive impairments in KS.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200438","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 transformational power of psychedelics: catalysts for creativity, consciousness, and mental health.","authors":"Xiubo Du, Jiantao Liu, Xiaohui Wang","doi":"10.1038/s41380-025-03291-8","DOIUrl":"https://doi.org/10.1038/s41380-025-03291-8","url":null,"abstract":"<p><p>Psychedelics, such as psilocybin, lysergic acid diethylamide (LSD), ketamine, and N,N-dimethyltryptamine (DMT), have captured the attention of scientists, artists, and seekers alike for their profound ability to alter consciousness and inspire creativity. The concept of \"creation\" encompasses multiple interpretations-ranging from generating novel ideas to fostering personal transformation. This perspective explores how psychedelics interact with the concept of creation, examining their role in enhancing artistic inspiration, facilitating spiritual experiences, and driving therapeutic breakthroughs in mental health treatment. By integrating findings from neurobiological research, clinical applications, and cultural analysis, we offer a holistic view of how psychedelics may catalyze innovative modes of thinking and awaken the mind's creative and transformative potential. As these substances gain prominence as tools for reshaping our understanding of consciousness and psychological healing, their broader integration into society requires careful consideration of legal complexities, ethical responsibilities, and cultural contexts to ensure their use is evidence-based, respectful, and responsibly guided.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200448","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":"Forebrain-specific loss of erythropoietin provokes compensatory upregulation of different EPO receptors.","authors":"Umer Javed Butt, Umut Çakır, Anne-Fleur Wildenburg, Yasmina Curto, Liu Ye, Vikas Bansal, Susann Boretius, Klaus-Armin Nave, Manvendra Singh, Hannelore Ehrenreich","doi":"10.1038/s41380-025-03230-7","DOIUrl":"https://doi.org/10.1038/s41380-025-03230-7","url":null,"abstract":"<p><p>The procognitive growth factor erythropoietin (EPO) and its canonical receptor, EPOR, have long been recognized to be expressed by most cell types in the brain. Cognitive domains, improved by injections of exogenous EPO or by endogenous, hypoxia-stimulated EPO, include important forebrain functions, namely attention, working memory, drive, and executive performance. To gain mechanistic insight into the involvement of forebrain-expressed EPO, we deleted EPO in mice using as specific cre-driver Emx1. Here, we report that these mutant mice act comparably to their wildtype littermates in a comprehensive behavioral test battery. Importantly, we find that the transcripts of both EPOR and a novel, brain-expressed EPO receptor, EphB4, respond to EPO deletion with compensatory upregulation. EphB4 expression in brain and its increase upon forebrain erasure of EPOR are confirmed by in situ hybridization and immunohistochemistry. The augmented expression of both EPOR and EphB4 and their regulatory intercorrelation may explain why EmxEPO mutants show an even superior performance in the most challenging working memory task. Using the previously published single-nuclei-RNA-seq dataset, we further confirm the suggested compensatory mechanism, wherein EPO loss or reduction drives elevated EPOR expression, adding another layer to the intricate regulation of EPO signaling in hippocampal pyramidal neurons. Collectively, these data may explain the lack of behavioral and negative cognitive consequences upon forebrain-wide EPO elimination.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200450","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 and validation of a prognostic model and risk calculator for the estimation of bipolar-spectrum disorder risk in hospitalised adolescents with non-psychotic/non-bipolar mental disorders.","authors":"Gonzalo Salazar de Pablo, Joaquim Radua, Grace Frearson, Allan H Young, Celso Arango, Ian Kelleher, Aditya Sharma, Peter J Uhlhaas, Marco Solmi, Paolo Fusar-Poli, Daniel Guinart, Christoph U Correll","doi":"10.1038/s41380-025-03244-1","DOIUrl":"https://doi.org/10.1038/s41380-025-03244-1","url":null,"abstract":"<p><p>We aimed to develop and validate a risk estimation model for developing bipolar-spectrum disorders (BSD) in psychiatrically hospitalized adolescents based on clinical characteristics, including putatively prodromal symptoms. Adolescent inpatients (ages = 12-18 years) with non-psychotic/non-BSD diagnoses were recruited for the Adolescent Mood Disorder and Psychosis Study (AMDPS), a longitudinal, prospective 5-year follow-up cohort. We assessed prevalence and severity of syndromal/subsyndromal psychopathology at baseline using the validated Bipolar Prodrome Symptom Interview and Scale-Prospective. We carried out machine learning analyses (Lasso-Cox regression analyses, LCR) to create a calculator to estimate the risk of developing BSD based on baseline demographic/comorbidity/illness/treatment characteristics. Of 105 adolescents (age = 15.6 ± 1.3 years, females = 72.4%), we observed that 18 developed BSD. The cumulated estimated risk of BSD was 5/22/29/36% at 1/2/3/4 years. BSD development was associated with presence of persistent depressive disorder (HR = 4.0, p < 0.018) at baseline, treatment with mood stabilizers (hazard ratio (HR) = 3.9, p = 0.006), and ADHD medications (HR = 3.3, p = 0.023). BSD development risk estimation calculator included the prevalence of inflated self-esteem/grandiosity (β = 0.83) and racing thoughts (β = 0.08) and the severity of overtalkativeness (β = 0.03) and increased energy (β = 0.04). For predicting BSD onset within the first 20 months, the area under the receiver operating characteristic curve (AUC) indicated acceptable to strong discrimination (cross-validation AUC = 0.72; bootstrap out-of-bag validation AUC = 0.86). Codes used in this study are provided in the R package \"easy.glmnet\". In conclusion, in this prognostic model/calculator, presence and severity of subthreshold (hypo)mania-like symptoms conferred increased risk of BSD development in youth, informing preventive efforts to identify individuals at risk for BSD and improve their outcomes.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192200","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 mPFC molecular clock mediates the effects of sleep deprivation on depression-like behavior and regulates sleep consolidation and homeostasis.","authors":"Wilf Gardner, David H Sarrazin, Martin Balzinger, Carole Marchese, Axelle Ragno, Chockalingam Ramanathan, Maxime Veleanu, Stefan Vestring, Claus Normann, Patrice Bourgin, Tsvetan Serchov","doi":"10.1038/s41380-025-03276-7","DOIUrl":"https://doi.org/10.1038/s41380-025-03276-7","url":null,"abstract":"<p><p>Disruptions in sleep, circadian rhythms, and neural plasticity are closely linked to the pathophysiology and treatment of depression. Acute sleep deprivation (SD) produces rapid but transient antidepressant effects, yet the underlying mechanisms remain poorly understood. Using a mouse model of stress-induced depression, we found altered sleep architecture, impaired sleep homeostasis, and disrupted day-night oscillations of the markers of glutamatergic plasticity - Homer1a and synaptic AMPAR expression in the medial prefrontal cortex (mPFC). These changes were accompanied by a blunted homeostatic response to SD. We further show that SD and ketamine, both rapid-acting antidepressants, exert opposing effects on mPFC circadian gene expression: SD enhances the expression of negative clock loop genes (e.g., Per, Cry), mirroring stress effects, while ketamine downregulates these same genes. Targeted deletion of the core clock gene Bmal1 in CaMK2a-expressing excitatory neurons of the mPFC disrupted sleep-wake architecture, elevated slow-wave activity, and abolished the behavioral and molecular (Homer1a) response to SD. Additionally, pharmacological activation of the clock repressor REV-ERB suppressed the antidepressant effects of SD. Our results demonstrate that the mPFC molecular clock is essential for the regulation of sleep consolidation and homeostasis, and mediates the effects of SD on behavior.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192254","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":"Asymmetric developmental bifurcations in polarized environments: a new class of human variants, which may include autism.","authors":"Laurent Mottron, Alix Lavigne-Champagne, Boris Bernhardt, Guillaume Dumas, Sébastien Jacquemont, David Gagnon","doi":"10.1038/s41380-025-03275-8","DOIUrl":"https://doi.org/10.1038/s41380-025-03275-8","url":null,"abstract":"<p><p>Inspired by discrete stable alternative states that often coexist with the dominant phenotypes of a species, we propose that asymmetric developmental bifurcations (ADB) may provide a biological framework for grouping autism together with some human alternative organizations rather than with disorders or diseases. These include minority embryological or obstetrical variants, such as twinning and breech presentation, as well as minority information processing variants, such as left-handedness and importantly prototypical autism. Four common contextual, developmental, adaptive, and mechanistic features unify these alternative conditions as ADBs: 1) ADBs occur in a dynamic system formed by an individual and his environment with two polarized stable solutions. 2) The bifurcation occurs in a critical period of development and is significantly shorter than the stable states that precede and follow it. 3) While the frequent branch of the ADB optimizes evolutionary success, its rare branch has an adaptive cost, which is still compatible with survival. 4) Both rare and frequent branches of the ADB are human possibilities, favoured without major/deleterious changes by familial and/or sexual predispositions. Framing autism as a categorical, alternative phenotypic prototype in a polarized choice between social bias and its absence, elucidates autism's recurrent divergence within the species, its developmental and information processing characteristics, and its adaptive challenges.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192272","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":"Crosstalk between alcohol use disorder and obesity: two sides of the same coin?","authors":"Lorenzo Leggio, Mehdi Farokhnia, Paul J Kenny, Marta Yanina Pepino, W Kyle Simmons","doi":"10.1038/s41380-025-03259-8","DOIUrl":"https://doi.org/10.1038/s41380-025-03259-8","url":null,"abstract":"<p><p>Investigating similarities and differences between alcohol use disorder (AUD) and obesity is important because both AUD and obesity are public health concerns and share neurobiological and periphery-brain mechanisms. Furthermore, AUD and obesity often present with similar medical consequences related to organ damage, including liver and cardiovascular diseases. There is also growing evidence of changes in alcohol drinking in people who undergo bariatric surgery for obesity. In this non-systematic critical review, we identified relevant articles through PubMed searches, previous knowledge, and recursive reference searching. A librarian also used PubMed and Google Scholar for additional relevant articles, using terms such as alcohol, metabolic disorders, obesity, glucagon-like peptide-1 (GLP-1), bariatric surgery, and gut-brain axis. We provide an overview of the neurobiological, pathophysiological, neuroimaging, and clinical features related to the overlap and crosstalk between AUD and obesity. We also provide a summary of the currently approved medications for obesity and those for AUD and note the potential for some of these medications to work for both disorders. Specific to the latter point, we place emphasis on GLP-1 therapies, given their recent approval for weight loss and the growing evidence suggesting their potential efficacy for AUD and other addictions. We further review studies of the relationship between bariatric surgery and AUD and discuss potential mechanisms and future directions. In summary, studying the overlap between obesity and AUD may shed light on the mechanisms underlying the development and maintenance of both diseases. This knowledge, in turn, may help identify new therapeutic targets for AUD, and possibly comorbid obesity and/or other metabolic disorders.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182239","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":"Frontotemporal dementia patient-derived iPSC neurons show cell pathological hallmarks and evidence for synaptic dysfunction and DNA damage.","authors":"Nadine Huber, Tomi Hietanen, Sami Heikkinen, Anastasia Shakirzyanova, Dorit Hoffmann, Hannah Rostalski, Ashutosh Dhingra, Salvador Rodriguez-Nieto, Sari Kärkkäinen, Marja Koskuvi, Eila Korhonen, Päivi Hartikainen, Katri Pylkäs, Johanna Krüger, Tarja Malm, Mari Takalo, Mikko Hiltunen, Jari Koistinaho, Anne M Portaankorva, Eino Solje, Annakaisa Haapasalo","doi":"10.1038/s41380-025-03272-x","DOIUrl":"https://doi.org/10.1038/s41380-025-03272-x","url":null,"abstract":"<p><p>Frontotemporal dementia (FTD) is the second most common cause of dementia in patients under 65 years, characterized by diverse clinical symptoms, neuropathologies, and genetic background. Synaptic dysfunction is suggested to play a major role in FTD pathogenesis. Disturbances in the synaptic function can also be associated with the C9orf72 repeat expansion (C9-HRE), the most common genetic mutation causing FTD. C9-HRE leads to distinct pathological hallmarks, such as C9orf72 haploinsufficiency and development of toxic RNA foci and dipeptide repeat proteins (DPRs). FTD patient brains, including those carrying the C9-HRE, are also characterized by neuropathologies involving accumulation of TDP-43 and p62/SQSTM1 proteins. This study utilized induced pluripotent stem cell (iPSC)-derived cortical neurons from C9-HRE-carrying or sporadic FTD patients and healthy control individuals. We report that the iPSC neurons derived from C9-HRE carriers developed typical C9-HRE-associated hallmarks, including RNA foci and DPR accumulation. All FTD neurons demonstrated increased cytosolic accumulation of TDP-43 and p62/SQSTM1 and changes in nuclear size and morphology. In addition, the FTD neurons displayed reduced number and altered morphologies of dendritic spines and significantly altered synaptic function indicated by a decreased response to stimulation with GABA. These structural and functional synaptic disturbances were accompanied by upregulated gene expression in the FTD neurons related to synaptic function, including synaptic signaling, glutamatergic transmission, and pre- and postsynaptic membrane, as compared to control neurons. Pathways involved in DNA repair were significantly downregulated in FTD neurons. Only one gene, NUPR2, potentially involved in DNA damage response, was differentially expressed between the sporadic and C9-HRE-carrying FTD neurons. Our results show that the iPSC neurons from FTD patients recapitulate pathological changes of the FTD brain and strongly support the hypothesis of synaptic dysfunction as a crucial contributor to disease pathogenesis in FTD.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145176762","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":"Maternal psychiatric disorders before, during, and after pregnancy: a national cohort study in Sweden.","authors":"Emma Bränn, Jerry Guintivano, Yihui Yang, Louise Lundborg, Marion Opatowski, Fang Fang, Unnur A Valdimarsdóttir, Emma Fransson, Alkistis Skalkidou, Yi Lu, Donghao Lu","doi":"10.1038/s41380-025-03212-9","DOIUrl":"https://doi.org/10.1038/s41380-025-03212-9","url":null,"abstract":"<p><p>Maternal mental health is a critical public health issue, yet the evidence on rates of incident psychiatric disorders before, during, and after pregnancy is limited. This study aimed to describe the calendar time trends and characterize and compare the risk of maternal psychiatric disorders before, during, and after pregnancy. Leveraging the national and regional registers in Sweden, we conducted a cohort study of all women who gave birth 2003-2019 in Sweden (1,799,010 pregnancies from 1,052,977 women). We identified any incident diagnosis of psychiatric disorders recorded during three periods: the preconceptional year, pregnancy, and the postpartum year. We calculated age and calendar year standardized incidence rate (SIR) of psychiatric disorders annually, and by week across three periods. We further estimated the incidence rate ratio (IRR) using the rate during corresponding preconceptional weeks as the reference. The SIR of maternal psychiatric disorder overall increased from 2003-2019, especially for preconceptional disorders. During the preconceptional year the weekly SIR of any psychiatric disorder was stable at around 25 per 1000 person-years. The SIR gradually decreased during pregnancy to a minimum of 4 per 1000 person-years and bounced back to the preconceptional levels during the postpartum year. This trend was similar in all subtypes of psychiatric disorders, except for depression and psychosis for which an increase was noted at 5-15 and 0-20 postpartum weeks, respectively. An increased incidence rate of maternal psychiatric disorder diagnosed before, during, and after pregnancy was found over time. Our findings suggest an increased risk of depression and psychosis shortly after delivery, although a lowered risk of other psychiatric disorders during and after pregnancy, compared to before pregnancy.</p>","PeriodicalId":19008,"journal":{"name":"Molecular Psychiatry","volume":" ","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138087","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}