Psychological Medicine最新文献

{"title":"Network localization of genetic risk for schizophrenia and bipolar disorder.","authors":"Shanwen Yao, Fan Mo, Zhonghao Rao, Yu Shi, Jiajia Zhu, Yongqiang Yu","doi":"10.1017/S0033291725101992","DOIUrl":"https://doi.org/10.1017/S0033291725101992","url":null,"abstract":"<p><strong>Background: </strong>There is a considerable overlap in clinical features and genetics between schizophrenia (SZ) and bipolar disorder (BD). Previous neuroimaging research has demonstrated common and distinct brain damage patterns between relatives (RELs) of SZ and BD patients, suggesting shared and differential genetic influences on the brain. Despite an increasing recognition that disorders localize better to distributed brain networks than individual brain regions, studies investigating network localization of genetic risk for SZ and BD are still lacking.</p><p><strong>Methods: </strong>To address this gap, we initially identified brain functional and structural damage locations in SZ- and BD-RELs from 103 published studies with 2364 SZ-RELs, 864 BD-RELs, and 4114 healthy controls. By applying novel functional connectivity network mapping to large-scale discovery and validation resting-state functional MRI datasets, we mapped these affected brain locations to four disorder-susceptibility networks.</p><p><strong>Results: </strong>SZ-susceptibility functional damage network primarily involved the executive control and salience networks, while its BD-counterpart principally implicated the default mode and basal ganglia networks. SZ-susceptibility structural damage network predominantly involved the auditory and default mode networks, yet its BD-counterpart mainly implicated the language and executive control networks. Although these networks showed cross-disorder inconsistencies when focusing on either imaging modality alone, the combined SZ- and BD-susceptibility brain damage networks had a substantially increased spatial similarity.</p><p><strong>Conclusions: </strong>These findings may support the concept that SZ and BD represent distinct diagnostic categories from a neurobiological perspective, helping to clarify the common network substrates via which the shared genetic mechanisms underlying both disorders give rise to their overlapping clinical phenotypes.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e299"},"PeriodicalIF":5.5,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network-dependent cortical thickness reductions following chronic methamphetamine use.","authors":"Yunkai Sun, Jun Wang, Jinsong Tang, Yanhui Liao","doi":"10.1017/S0033291725102067","DOIUrl":"https://doi.org/10.1017/S0033291725102067","url":null,"abstract":"<p><strong>Background: </strong>Cortical thickness reductions associated with chronic methamphetamine use exhibit a non-uniform spatial distribution across brain regions. A potential neurobiological mechanism underlying for this heterogeneous pattern may involve the structural and functional organization of cortical connectivity networks, which could mediate the propagation of neuroanatomical alterations. Here, we aimed to explore how brain network architecture constrains cortical thickness alterations and their clinical relevance.</p><p><strong>Methods: </strong>The 3D-T1 images were acquired from 139 patients with methamphetamine use disorder (MUD) and 119 sex- and age-matched healthy controls. We first characterized distributed cortical thinning patterns in patients with MUD, then evaluated the relationships between regional atrophy and (1) multimodal nodal centrality measures (structural, morphological, and functional) and (2) atrophy profiles of structural connected neighbors. Individual network-weighted cortical abnormality maps were used to identify distinct MUD biotypes and related to clinical features through k-means clustering and partial least squares regression.</p><p><strong>Results: </strong>Cortical thinning patterns demonstrated significant associations with nodal centrality across all modalities, as well as cortical thinning of connected neighbors revealing a network-dependent atrophy architecture. Fronto-temporal regions emerged as critical epicenters, showing both high nodal centrality and strong correlations with connected neighbors' thinning severity. We found that the individual differences in network-weighted cortical abnormality corresponded to clinical symptom variability, and distinguished two MUD biotypes associated with drug use.</p><p><strong>Conclusions: </strong>Our findings suggest that cortical thinning in MUD is influenced by the brain connectome architecture, providing a mechanistic framework for understanding individual variability in addiction progression.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e296"},"PeriodicalIF":5.5,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of childhood irritability and parenting profiles with youth suicide attempt: a longitudinal person-centered approach.","authors":"Cassandra Zephirin, Marie-Claude Geoffroy, Eszter Szekely, Léa C Perret, Michel Boivin, Richard E Tremblay, Sylvana M Côté, Massimiliano Orri","doi":"10.1017/S003329172510192X","DOIUrl":"https://doi.org/10.1017/S003329172510192X","url":null,"abstract":"<p><strong>Background: </strong>Childhood irritability and harsh parenting are associated with youth suicide attempts. Parents' harsh reactions have been associated with children's irritable behavior. While studies have shown individual associations of irritability and parenting behaviors with suicide risk, few have considered these factors jointly. We aimed to identify profiles of children based on irritability and parenting during childhood and examine their associations with youth suicide attempt.</p><p><strong>Methods: </strong>Participants (<i>N</i> = 1626) were from the Québec Longitudinal Study of Child Development. Mothers reported on childhood irritability, harsh parenting, and positive parenting between ages 3.5 and 8; youth self-reported suicide attempt between ages 13 and 23.</p><p><strong>Results: </strong>We identified four profiles based on the joint development of irritability and parenting during childhood: (1) low irritability, low harsh parenting, and high positive parenting (30.3%); (2) moderate irritability, moderate harsh parenting, and high positive parenting (28.4%); (3) moderate irritability, moderate harsh parenting, and low positive parenting (26.6%); and (4) high irritability, high harsh parenting, and low positive parenting (14.8%). In logistic regression analyses, only children in the high irritability, high harsh parenting, and low positive parenting profile had higher odds of attempting suicide (OR = 2.51; 95% CI = 1.55-4.09) compared to those in the low irritability, low harsh parenting, and high positive parenting profile. This association remained significant (OR = 1.80; 95% CI = 1.03-3.15) in models adjusting for covariates.</p><p><strong>Conclusion: </strong>Children with chronically high irritability were also those experiencing the harshest parenting and the least positive parenting, as well as those most at risk of suicide attempt. Targeting both child and parental behavior may maximize suicide prevention efforts among children with high irritability.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e292"},"PeriodicalIF":5.5,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do complex psychometric analyses really matter? Comparing multiple approaches using individual participant data from antidepressant trials.","authors":"David Byrne, Frank Doyle, Susan Brannick, Robert M Carney, Pim Cuijpers, Alexandra L Dima, Kenneth E Freedland, Suzanne Guerin, David Hevey, Bishember Kathuria, Emma Wallace, Fiona Boland","doi":"10.1017/S0033291725101785","DOIUrl":"https://doi.org/10.1017/S0033291725101785","url":null,"abstract":"<p><strong>Background: </strong>Psychometric methods are used to remove underperforming items and reduce error in existing measures, albeit different approaches can produce different results. This study aimed to determine the implications of applying different psychometric methods for clinical trial outcomes.</p><p><strong>Methods: </strong>Individual participant data from 15 antidepressant treatment trials from Vivli.org were analyzed. Baseline (pretreatment) and 8-week (range 4-12 weeks) outcome data from the Montgomery-Asberg Depression Rating Scale were subjected to best-practice factor analysis (FA), item response theory (IRT), and network analysis (NA) approaches. Trial outcomes for the original summative scores and psychometric-model scores were assessed using multilevel models. Percentage differences in Cohen's <i>d</i> effect sizes for the original summative and psychometrically modeled scores were the effects of interest.</p><p><strong>Results: </strong>Each method produced unidimensional models, but the modified scales varied from 7 to 10 items. Treatment effects (<i>d</i> = 0.072) were unchanged for IRT (10 items), decreased by 1.3%-2.8% (eight-item abbreviated <i>d</i> = 0.070; weighted score <i>d</i> = 0.071) for NA, and increased by 11%-12.5% (seven-item abbreviated model <i>d</i> = 0.081; weighted score <i>d</i> = 0.080) for FA.</p><p><strong>Discussion: </strong>IRT and NA yielded negligible differences in effect outcomes relative to original trials. FA increased effect sizes and may be the most effective method for identifying the items on which placebo and treatment group outcomes differ.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e289"},"PeriodicalIF":5.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive trajectories and dementia risk in patients with schizophrenia spectrum versus affective disorders.","authors":"Kathy Y Liu, Gayan Perera, Robert Howard, Christoph Mueller","doi":"10.1017/S0033291725101864","DOIUrl":"https://doi.org/10.1017/S0033291725101864","url":null,"abstract":"<p><strong>Background: </strong>Schizophrenia spectrum disorders confer an increased and earlier dementia diagnosis risk, but the relative timing and course of cognitive decline compared to individuals with affective disorders is unclear.</p><p><strong>Methods: </strong>This retrospective study used de-identified electronic patient records to compare cognitive trajectories from the first recorded MMSE, representing the earliest cognitive concerns in relation to a possible dementia syndrome, and subsequent dementia risk between patients with a schizophrenia spectrum and primary affective disorder diagnosis. Patients had at least two MMSE scores recorded at least 6 months apart. We examined annual MMSE change from the first recorded MMSE, dementia risk, dementia subtypes, and rates of dementia assessment and treatment.</p><p><strong>Results: </strong>Compared to affective disorders (<i>n</i> = 2,264; 71.1 years), schizophrenia spectrum disorders (<i>n</i> = 1,217; 65.0 years) showed earlier initial MMSE scores (by 6.1 years, 95% CI = 5.2-7.0), earlier dementia diagnoses (by 2.3 years, 95% CI = 0.9-3.7) but lower dementia risk (adjusted HR = 0.81; 95% CI = 0.69-0.95). Cognitive decline rates and dementia subtype diagnoses did not differ between affective and schizophrenia spectrum disorders, but it took longer for schizophrenia spectrum disorder patients to receive a dementia diagnosis (5.6 vs. 4.4 years). Anti-dementia medication was less likely to be prescribed in patients with schizophrenia versus depression.</p><p><strong>Conclusions: </strong>Cognitive concerns in older individuals with schizophrenia spectrum disorders arise from around 63 years and are associated with earlier dementia risk versus older individuals with affective disorders. Findings emphasize the importance of targeted dementia prevention and treatment strategies in these individuals and the need to reduce the existing inequity of access to dementia services.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e286"},"PeriodicalIF":5.5,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fluoxetine for anorexia nervosa after weight restoration: moderation of effect by depression.","authors":"E Caitlin LLoyd, Trevor Griffen, Yuanjia Wang, Evelyn Attia, B Timothy Walsh","doi":"10.1017/S003329172510127X","DOIUrl":"https://doi.org/10.1017/S003329172510127X","url":null,"abstract":"<p><strong>Background: </strong>Pharmacological efforts to treat anorexia nervosa (AN) have predominantly repurposed medications that treat conditions with overlapping symptoms and yielded generally disappointing results. Despite limited empirical support, SSRIs are often prescribed to patients with AN. Whether SSRIs are effective in a subgroup of individuals with AN, such as those with depression, is not known.</p><p><strong>Methods: </strong>A secondary analysis of a randomized trial of fluoxetine versus placebo for relapse prevention in AN was conducted. Participants (<i>n</i> = 92) were weight-restored women with AN who completed the Beck Depression Inventory (BDI) at the time of randomization. BDI scores were dichotomized to reflect moderate/severe depression (BDI > 20, <i>n</i> = 26). A Cox Proportional Hazards model estimated the association of the level of depression, medication, and their interaction with time to relapse. Mixed effects models examined the effects of medication on symptom trajectories in high versus low depression groups and whether depression severity modified the effect of the drug on symptom trajectory.</p><p><strong>Results: </strong>There was a significant interaction between medication and depression severity in time to relapse (hazard ratio = 0.46, 95% CI: [0.25, 0.85], <i>p</i> = .01). Depression severity modified the effect of fluoxetine on the time course of symptoms of depression (<i>β</i> = -0.27, 95% CI: [-0.42,-0.12], <i>p</i> = 0.001) and bulimia (<i>β</i> = -0.15, 95% CI: [-0.25,-0.05], <i>p</i> = 0.004) in the twelve month follow-up period.</p><p><strong>Conclusions: </strong>Fluoxetine was more effective than placebo in reducing relapse among more depressed, weight-restored individuals with AN. These results require replication but provide support for the use of antidepressant medication for patients with AN who remain depressed following weight restoration.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e290"},"PeriodicalIF":5.5,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145192758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mental health outcomes associated with military sexual trauma in serving and ex-servicewomen: A systematic review.","authors":"Tamara Obradovic, Sarah Rabin, Dominic Murphy, Nicola T Fear, Marie-Louise Sharp","doi":"10.1017/S003329172510175X","DOIUrl":"https://doi.org/10.1017/S003329172510175X","url":null,"abstract":"<p><p>Military sexual trauma (MST) (sexual harassment or sexual assault experienced during military service) is associated with adverse mental health outcomes. This systematic review assessed international, published, peer-reviewed academic literature and aimed to (1) identify the mental health outcomes of MST for serving and ex-servicewomen, (2) understand whether sexual harassment and sexual assault impact mental health differently, and (3) identify individual differences that may influence mental health outcomes. Included sources were peer reviewed, primary research, which investigated MST as a predictor of mental health outcome(s) in women. Database searches (June 2023, May 2024, and March 2025) yielded 63 studies, most of which (<i>n</i> = 58) were conducted in the United States and used quantitative methods (<i>n</i> = 60). A narrative synthesis approach facilitated data synthesis. Quantitative studies identified associations between MST and adverse mental health outcomes, with qualitative studies providing further context to these associations. Military sexual assault appeared to have a stronger relationship with adverse mental health than other MST experiences. Posttraumatic stress disorder and depression symptoms were associated with further outcomes, such as suicidality, disordered eating, and substance use. Some additional trauma exposures exacerbated the impacts of MST on mental health, whilst social support mitigated negative mental health outcomes. This review identifies significant mental health impacts of MST and highlights the importance of formal and informal support for serving and ex-servicewomen with MST experiences.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e287"},"PeriodicalIF":5.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ethical issues with psychedelic-assisted treatments in psychiatry: A systematic scoping review.","authors":"Chiara Caporuscio, Christopher Poppe, Astrid Gieselmann, Dimitris Repantis","doi":"10.1017/S0033291725101761","DOIUrl":"https://doi.org/10.1017/S0033291725101761","url":null,"abstract":"<p><p>Based on promising preliminary results from clinical trials, it seems likely that psychedelic substances (classic serotonergic psychedelics, such as psilocybin, and entactogens, such as MDMA) will be introduced into psychiatry as psychedelic-assisted therapy. This also raises a range of ethical questions that urgently need to be addressed before widespread roll-out in society. This scoping review fills a gap in the literature by providing an overview of these ethical issues using a systematic search, presentation, and descriptive analysis of ethical issues in psychedelic-assisted treatments. It includes peer-reviewed studies pertaining to human study participants and psychiatric patients (population), which discuss ethical issues (concept) of psychedelic treatments (context) in clinical trials and other clinical applications. The systematic search included several databases: MEDLINE, PsycInfo, CINAHL, HeinOnline, and PsycArticles. The search strategy, including all identified keywords and index terms, was adapted for each included database. The search was completed in June 2025 and studies published until then in any language were included. After an iterative process of inductive and deductive coding of ethical issues, the scoping review comprises seven themes related to the ethics of psychedelic-assisted treatments: (1) safety and patient well-being, (2) therapeutic relationships, (3) informed consent, (4) equity and access, (5) research ethics, (6) special contexts, and (7) societal and cultural implications. The results can be used to inform and stimulate further discussion and in-depth research on the ethics of psychedelic-assisted treatments, possibly leading to more nuanced debate surrounding a safer and more ethical implementation of psychedelic-assisted treatments in the future.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e284"},"PeriodicalIF":5.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Motor circuits and beyond: Functional connectivity related to psychomotor syndromes in depression.","authors":"Qunjun Liang, Zhifeng Zhou, Ying Li, Shengli Chen, Shiwei Lin, Xiaoshan Lin, Yingli Zhang, Bo Peng, Ziyun Xu, Gangqiang Hou, Yingwei Qiu","doi":"10.1017/S0033291725101852","DOIUrl":"https://doi.org/10.1017/S0033291725101852","url":null,"abstract":"<p><strong>Background: </strong>Psychomotor disturbance (PmD) is prevalent in major depressive disorder (MDD), with neural substrates implicated in disrupted motor circuits and the interaction to non-motor cortex. Our objective is to explore the functional connectivity pattern underlying PmD using functional magnetic resonance imaging (fMRI).</p><p><strong>Methods: </strong>A total of 150 patients with MDD and 91 healthy controls (HCs) were included in this study. The patients were categorized into psychomotor (pMDD, n = 107) and non-psychomotor (npMDD, n = 43) groups based on the Hamilton Depression Rating Scale. Seed-based connectivity (SBC) analysis was conducted using predefined somatomotor and cerebellar network (SMN and CN) coordinates as seeds, to assess group differences and symptom correlations. Subsequently, we correlated the group-contrast SBC map with existing neurotransmitter maps to explore the neurochemical basis.</p><p><strong>Results: </strong>In pMDD patients compared to HC, we observed decreased connectivity, especially between the SMN and frontal cortex, within the bilateral SMN, and between the CN and right precentral cortex. Meanwhile, connectivity increased between the SMN and the middle cingulate cortex and between the CN and left precentral cortex in pMDD relative to npMDD and HC. Connectivity between the SMN and angular gyrus was positively correlated with the severity of PmD. Additionally, the aberrant SBC patterns in pMDD were linked to the distribution of dopamine D1 and D2 receptors.</p><p><strong>Conclusions: </strong>This study provides insights into the aberrant connectivity within the motor circuits and its interactions with non-motor regions in PmD. It also suggests a potential role for dopaminergic dysregulation in the connectivity abnormalities associated with PmD.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e285"},"PeriodicalIF":5.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic risk scores of psychiatric phenotypes are associated with depression risk in a prospective Dutch population-based cohort.","authors":"Amy Hofman, Bahar Sedaghati-Khayat, Annabel Vreeker, M Arfan Ikram, André G Uitterlinden, Joyce B J van Meurs, Jeroen G J van Rooij, Annemarie I Luik","doi":"10.1017/S0033291725101943","DOIUrl":"https://doi.org/10.1017/S0033291725101943","url":null,"abstract":"<p><strong>Background: </strong>Genetic risk scores hold potential for predicting depression in the general population. These scores must be validated for their associations with relevant characteristics of depression-related phenotypes, such as severity. We validated a genome-wide risk score (GRS) and a restricted polygenic risk score (PRS) for depression based on a meta-analysis of three genome-wide association studies and assessed their associations with depression in three subcohorts of middle-aged and older adults from the Dutch population-based Rotterdam Study.</p><p><strong>Methods: </strong>Of participants with genotype data, 9,198 had longitudinally measured data (mean follow-up: 11.3 years) on three depression-related phenotypes (depressive symptoms, depressive syndrome, and major depressive disorder). Generalized linear models estimated the associations of standardized GRS and PRS with depression phenotypes per subcohort and were then meta-analyzed. One unit of the GRS/PRS represents 1 standard deviation, following <i>z</i>-transformation per cohort.</p><p><strong>Results: </strong>A one unit higher GRS and PRS were associated with any longitudinally measured depression phenotype (odds ratio (OR)_GRS = 1.20 [1.15-1.26], OR_PRS = 1.10 [1.05-1.16]). Effect sizes were highest for episodes of major depressive disorder: for individuals with the 10% highest GRS and PRS, the ORs were 1.99 [1.53-2.57] and 1.51 [1.13-1.99], respectively, compared to the middle 50% of the distribution.</p><p><strong>Conclusions: </strong>The GRS and PRS for depression showed modest associations across multiple depression-related phenotypes in a population-based setting. The strength of associations generally increased with the severity of the phenotype. While effect sizes were generally larger for GRS compared to PRS, the difference was mostly not statistically significant.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e288"},"PeriodicalIF":5.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}