Psychological Medicine最新文献

{"title":"Longitudinal associations between gaming and academic motivation during middle childhood.","authors":"Gabriel Arantes Tiraboschi, Gabrielle Garon-Carrier, Sheri Madigan, Jonathan Smith, Rachel Surprenant, Caroline Fitzpatrick","doi":"10.1017/S0033291725101153","DOIUrl":"10.1017/S0033291725101153","url":null,"abstract":"<p><strong>Background: </strong>Child video game playing (\"gaming\") may lead to decreased child academic motivation. Conversely, children with low academic motivation may seek fulfillment through gaming. We examined bidirectional associations between child gaming and academic motivation across middle childhood.</p><p><strong>Methods: </strong>Our analyses are based on 1,631 children (boys = 785) followed in the context of the Quebec Longitudinal Study of Child Development. Data on gaming and academic motivation were collected repeatedly at ages 7, 8, and 10. Measures of child gaming were parent-reported and reflect daily video game playing time. Measures of academic motivation were child self-reported and reflect enjoyment in learning mathematics, reading, and writing. To disentangle the directionality of associations, we estimated a random-intercept cross-lagged panel model to estimate bidirectional, within-person associations between gaming and academic motivation in a cohort of school-aged Canadian children.</p><p><strong>Results: </strong>Our results revealed unidirectional associations whereby more frequent gaming by boys at age 7 years predicted lower academic motivation at age 8 years (<i>β</i> = -.11, 95% confidence interval [CI]: -.22 to -.01), and similarly, gaming by boys at age 8 years predicted lower academic motivation at age 10 years (<i>β</i> = -.10, 95% CI: -.19 to -.01). Changes in boys' academic motivation did not contribute to subsequent changes in gaming. There were no associations between gaming and academic motivation for girls.</p><p><strong>Conclusions: </strong>More time devoted to gaming among school-aged boys is associated with reduced academic motivation during a critical developmental period for the development of academic skills. Fostering healthy gaming habits may help promote academic motivation and success.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e235"},"PeriodicalIF":5.5,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of antipsychotic medication inception in antipsychotic-naive youth at clinical high risk for psychosis.","authors":"Hesham Mukhtar, Dolores Zhou, Emily A Farina, Abhishek Saxena, John Cahill, Jean Addington, Carrie E Bearden, Kristen S Cadenhead, Tyrone D Cannon, Barbara A Cornblatt, Matcheri S Keshwan, Daniel H Mathalon, Diana O Perkins, William S Stone, Youngsun T Cho, Albert R Powers, Elaine F Walker, Scott W Woods","doi":"10.1017/S0033291725101372","DOIUrl":"10.1017/S0033291725101372","url":null,"abstract":"<p><strong>Background: </strong>Antipsychotic (AP) medication in individuals at clinical high risk for psychosis (CHR-P) is not routinely recommended by clinical guidelines but is commonly prescribed. Since little is known about the predictors of AP inception in CHR-P, we analyzed data from two observational cohorts.</p><p><strong>Methods: </strong>To avoid baseline predictors being confounded by previous treatment, participants were selected for analysis from the 764 participants at CHR-P enrolled in NAPLS-2 and the 710 enrolled in NAPLS-3 by excluding those with lifetime histories of AP use. Baseline clinical variables available in both studies were employed as predictors of subsequent AP inception over the next 6 months in univariable and multivariable analyses.</p><p><strong>Results: </strong>Preliminary analyses indicated no important effects of sample. The final combined population included 79 AP inception participants and 580 participants who did not have AP inception. The AP medications most commonly prescribed were risperidone, aripiprazole, and quetiapine. Univariable analyses identified seven significant predictors of AP inception. The final logistic regression model including these variables was highly significant (χ² = 36.53, df = 7, <i>p</i> = <0.001). Three variables (current <i>major depression</i>, fewer education years, and current benzodiazepine use) emerged as significant independent predictors of AP inception.</p><p><strong>Conclusion: </strong>This study is the first to determine baseline characteristics that predict subsequent AP initiation in CHR-P. Some AP use in CHR-P appears to be intended as augmentation of antidepressant treatment for comorbid major depression. Some prescribers may not have detected the attenuated positive symptoms characteristic of CHR-P since their severity did not significantly predict AP inception.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e241"},"PeriodicalIF":5.5,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-ancestral genome-wide association study of clinically defined nicotine dependence reveals strong genetic correlations with other substance use disorders and health-related traits.","authors":"Emma C Johnson, Dongbing Lai, Jared V Balbona, Alex P Miller, Alexander S Hatoum, Joseph D Deak, Mariela Jennings, David A A Baranger, Marco Galimberti, Kittipong Sanichwankul, Thorgeir Thorgeirsson, Sarah M C Colbert, Keyrun Adhikari, Anna R Docherty, Louisa Degenhardt, Tobias Edwards, Louis Fox, Alexandros Giannelis, Paul W Jeffries, Tellervo Korhonen, Claire L Morrison, Yaira Z Nunez, Teemu Palviainen, Mei-Hsin Su, Pamela N Romero Villela, Leah Wetherill, Emily A Willoughby, Stephanie M Zellers, Laura J Bierut, Jadwiga Buchwald, William E Copeland, Robin P Corley, Naomi P Friedman, Tatiana M Foroud, Nathan A Gillespie, Ian R Gizer, Andrew C Heath, Ian B Hickie, Jaakko Kaprio, Matthew C Keller, James J Lee, Penelope Lind, Pamela A Madden, Hermine H M Maes, Nicholas G Martin, Matt McGue, Sarah E Medland, Elliot C Nelson, John Pearson, Bernice Porjesz, Michael C Stallings, Scott Vrieze, Kirk C Wilhelmson, Henry R Kranzler, Raymond K Walters, Renato Polimanti, Robert Malison, Hang Zhou, Kari Stefansson, Sandra Sanchez-Roige, Marc Potenza, Apiwat Mutirangura, Vorasuk Shotelersuk, Rasmon Kalayasiri, Howard J Edenberg, Joel Gelernter, Arpana Agrawal","doi":"10.1017/S0033291725100883","DOIUrl":"10.1017/S0033291725100883","url":null,"abstract":"<p><strong>Background: </strong>Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement.</p><p><strong>Methods: </strong>We conducted a genome-wide association study (GWAS) of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry [EUR], 10,231 of African ancestry, and 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes.</p><p><strong>Results: </strong>We replicated the well-known association at the <i>CHRNA5</i> locus (lead single-nucleotide polymorphism [SNP]: rs147144681, <i>p</i> = 1.27E-11 in EUR; lead SNP = rs2036527, <i>p</i> = 6.49e-13 in cross-ancestry analysis). DSM-NicDep showed strong positive genetic correlations with cannabis use disorder, opioid use disorder, problematic alcohol use, lung cancer, material deprivation, and several psychiatric disorders, and negative correlations with respiratory function and educational attainment. A polygenic score of DSM-NicDep predicted DSM-5 tobacco use disorder criterion count and all 11 individual diagnostic criteria in the independent National Epidemiologic Survey on Alcohol and Related Conditions-III sample. In genomic structural equation models, DSM-NicDep loaded more strongly on a previously identified factor of general addiction liability than a \"problematic tobacco use\" factor (a combination of cigarettes per day and nicotine dependence defined by the Fagerström Test for Nicotine Dependence). Finally, DSM-NicDep showed a strong genetic correlation with a GWAS of tobacco use disorder as defined in electronic health records (EHRs).</p><p><strong>Conclusions: </strong>Our results suggest that combining the wide availability of diagnostic EHR data with nuanced criterion-level analyses of DSM tobacco use disorder may produce new insights into the genetics of this disorder.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e234"},"PeriodicalIF":5.5,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12360691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of schizophrenia-associated risk genes on brain functional networks and executive deficits: a study of individuals with schizophrenia and genetic high risk.","authors":"Ting Sun, Yue Zhu, Pengfei Zhao, Wenhui Zhao, Linzi Liu, Lili Tang, Mengxue Li, Yixiao Xu, Pengshuo Wang, Yifan Zhang, Yuning Zhou, Yifang Zhou, Jujiao Kang, Xiaohong Gong, Fei Wang, Yanqing Tang","doi":"10.1017/S0033291725101177","DOIUrl":"10.1017/S0033291725101177","url":null,"abstract":"<p><strong>Background: </strong>Schizophrenia (SCZ) and genetic high-risk (GHR) individuals exhibit deficits in brain functional networks and cognitive function, potentially impacted by SCZ risk genes. This study aims to delineate these impairments in SCZ and GHR individuals, and further explore how risk genes affect brain networks and executive function.</p><p><strong>Methods: </strong>A total sample size of 292 participants (100 SCZ, 68 GHR, and 124 healthy controls [HCs]) in the study. The Wisconsin Card Sorting Test (WCST) and resting-state functional magnetic resonance imaging (rs-fMRI) are utilized to evaluate executive function and brain network topology. SCZ-related polygenic risk scores (SCZ-PRS) were used to evaluate genetic risk levels. WCST and PRS were not applied to all participants.</p><p><strong>Results: </strong>Significant reductions in nodal efficiency and degree centrality (D_nodal) were observed within the right median cingulate and paracingulate gyri (MCPG_R) in both SCZ and GHR groups, compared to HCs. There were significant correlations between SCZ-PRS, D_nodal in MCPG_R, and WCST scores. Moreover, D_nodal in MCPG_R completely mediated the relationship between SCZ-PRS and executive function. The enrichment analysis of these risk genes indicates their involvement in biological processes of signal transduction and synaptic transmission.</p><p><strong>Conclusions: </strong>This study highlights the pivotal role of impaired cingulate function in mediating the effects of genetic risks on executive deficits, offering new insights into the genetic-neuro-cognitive nexus in schizophrenia and potential targets for clinical interventions.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e240"},"PeriodicalIF":5.5,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does early non-improvement predict treatment failure in pharmacotherapy for obsessive-compulsive disorder? A diagnostic test accuracy meta-analysis with individual participant data.","authors":"Sem Cohen, Jasper Brian Zantvoord, Ton de Boer, Taina Mattila, Guido van Wingen, Damiaan Denys","doi":"10.1017/S0033291725101335","DOIUrl":"10.1017/S0033291725101335","url":null,"abstract":"<p><strong>Background: </strong>In the treatment of obsessive-compulsive disorder (OCD) with antidepressant medication, the earliest reliable indication of treatment failure remains uncertain. We investigated if non-improvement following 4 weeks of treatment predicts nonresponse at the end of the trial.</p><p><strong>Methods: </strong>We conducted a random-effects bivariate diagnostic accuracy study using individual patient data from industry-sponsored short-term trials of adults with OCD receiving selective serotonin reuptake inhibitors or clomipramine, submitted for marketing approval. The primary outcome was accuracy of non-improvement (<25% reduction on the Yale-Brown Obsessive Compulsive Scale [YBOCS] after 4 weeks) in predicting nonresponse (<35% YBOCS reduction at trial endpoint [10-13 weeks]). Secondary outcomes were accuracy of non-improvement after 6 weeks, nonresponse after 8 weeks, and inclusion of Clinical Global Impression Scale - Improvement in definitions of improvement and response. We performed meta-regressions for sex, age, severity, trial duration, dosing regimen, and compound.</p><p><strong>Results: </strong>In 11 studies totaling 1,753 patients, non-improvement at week 4 predicted subsequent nonresponse (positive predictive value, PPV) in 86% of cases (95% confidence interval [CI] = 83-88%). Sensitivity was 78%, specificity was 70%, and the negative predictive value was 60%. Secondary outcomes showed similar PPV after 6 weeks and a PPV of 93% for nonresponse after 8 weeks. Predictive accuracy was significantly higher in men relative to women (<i>β</i> = -0.64, 95% CI = -1.12 to -0.16, <i>p</i> = 0.0089).</p><p><strong>Conclusions: </strong>Patients with OCD who do not improve after 4 weeks of antidepressants will likely not respond to short-term treatment. Thus, a change in strategy should be considered after 4 weeks without treatment benefits.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e237"},"PeriodicalIF":5.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Dismantling Study of Comprehensive Cognitive Remediation for Improving Employment Outcomes: What is the Role of Computer Cognitive Training? - CORRIGENDUM.","authors":"Susan R McGurk, Kim T Mueser, Haiyi Xie, Philippe Bloch, Nicole R DeTore, Nicole Pashka, Susan Guarino, Anabelle Ruiz, Clara Elliot, Heather Gagnon, Edward Bailey, Virginia Fraser, Jason Welsh, Harry Cunningham, Lisa Razzano, Rosemarie Wolfe, Robert E Drake","doi":"10.1017/S0033291725101487","DOIUrl":"10.1017/S0033291725101487","url":null,"abstract":"","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e236"},"PeriodicalIF":5.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regular sleep patterns, not just duration, critical for mental health: association of accelerometer-derived sleep regularity with incident depression and anxiety.","authors":"Dong-Run Li, Zheng-Xuan Li, Ming-Hui Li, Bang-Quan Liu, Qian Fang, Jia-Cheng Liu, Wen-Rui Zheng, Ting-Ting Gong, Shan-Yan Gao, Qi-Jun Wu","doi":"10.1017/S0033291725101281","DOIUrl":"10.1017/S0033291725101281","url":null,"abstract":"<p><strong>Background: </strong>Depression and anxiety are prevalent mental health disorders. While sleep duration has been extensively studied, sleep regularity may play a critical role. We aimed to examine associations between objectively measured sleep regularity and incident depression and anxiety and to investigate whether meeting recommended sleep duration modifies these associations.</p><p><strong>Methods: </strong>In 79,666 UK Biobank participants without baseline depression or anxiety, wrist accelerometers worn for 7 days yielded a sleep regularity index (SRI) and average sleep duration. SRI was categorized as irregular (≤51), moderately irregular (52-70), or regular (≥71). Sleep duration was classified by age-specific recommendations (7-9 hours for ages 18-64 years; 7-8 hours for over 65 years). Cox regression models assessed associations between sleep parameters and mental health outcomes.</p><p><strong>Results: </strong>During a median follow-up of 7.5 years, 1,646 participants developed depression, and 2,097 developed anxiety. Compared to irregular sleepers, regular sleepers had a 38% lower depression risk (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.52-0.73) and a 33% lower anxiety risk (HR, 0.67; 95%CI, 0.58-0.77). Participants with both irregular sleep and nonrecommended duration exhibited the highest risks (depression HR, 1.91; 95%CI, 1.55-2.35; anxiety HR, 1.61; 95%CI, 1.35-1.93). Notably, irregular sleepers who met duration guidelines still faced elevated risks (depression HR, 1.48; 95%CI, 1.18-1.86; anxiety HR, 1.35; 95%CI, 1.11-1.64).</p><p><strong>Conclusions: </strong>Greater sleep regularity is independently associated with lower depression and anxiety risk regardless of sleep duration, suggesting that sleep-wake consistency should be considered in mental health promotion strategies alongside traditional sleep duration recommendations.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e239"},"PeriodicalIF":5.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Measuring resilience to chronic pain in population surveys using hair cortisol.","authors":"Tarani Chandola, Stephanie Cahill, Wanying Ling, Meena Kumari","doi":"10.1017/S0033291725101049","DOIUrl":"10.1017/S0033291725101049","url":null,"abstract":"<p><strong>Background: </strong>Chronic pain activates the HPA axis stress response resulting in the release of cortisol, although empirical associations are often contradictory. Quantile regression models of hair cortisol may help us measure HPA-axis dysregulation more accurately and establish more robust associations with chronic pain. We also examined whether people with chronic pain characterised by HPA-axis dysregulation are at risk of future mental ill-health.</p><p><strong>Methods: </strong>This study examined data from the English Longitudinal Study of Ageing (ELSA, <i>n</i> = 4,560) and the UK Household Longitudinal Survey-Innovation Panel (UKHLS-IP, <i>n</i> = 473) to assess whether quantile regression methods enable us to assess more robust associations between hair cortisol and chronic pain, and whether older adults with chronic pain characterised by HPA-axis dysregulation are at risk of future mental ill-health.</p><p><strong>Results: </strong>In ELSA, chronic pain was associated with a 15% (CI: 6%-23%) increase in cortisol at the 10th percentile of the hair cortisol distribution among older adults and a 19% (CI: 2%-37%) increase at the 80th percentile, but no association was found at the 30th or 40th percentiles. Having a low cortisol response to chronic pain protected against the recurrence of depression. These patterns of association were replicated in the UKHLS-IP sample.</p><p><strong>Conclusions: </strong>The associations demonstrated across two longitudinal population surveys from the UK indicate that quantile regression analysis of hair cortisol may be useful in identifying individuals resilient to chronic pain. Hair cortisol is a promising biomarker that can be measured in population studies to quantify the stress response and resilience to future mental ill-health.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e201"},"PeriodicalIF":5.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Misclassifying and differentiating metacognitive therapy: conceptual and methodological issues in Stenzel et al.","authors":"Robin Bailey","doi":"10.1017/S0033291725101463","DOIUrl":"10.1017/S0033291725101463","url":null,"abstract":"","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e238"},"PeriodicalIF":5.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The outcome of major psychiatric and substance use disorders as an index of genetic risk and genetic heterogeneity.","authors":"Kenneth S Kendler, Henrik Ohlsson, Jan Sundquist, Kristina Sundquist","doi":"10.1017/S0033291725101116","DOIUrl":"10.1017/S0033291725101116","url":null,"abstract":"<p><strong>Background: </strong>We investigate whether, in Swedish national registers, social and psychiatric outcomes for six major psychiatric and substance disorders - drug use disorder (DUD), alcohol use disorder (AUD), major depression (MD), bipolar disorder (BD), anxiety disorder (AD), and schizophrenia (SZ) - reflect the primary genetic risk for each disorder and the level of genetic heterogeneity.</p><p><strong>Methods: </strong>We utilize Genetic Risk Ratios - defined as the ratio of the genetic risk for secondary disorders to the genetic risk for the primary disorder - derived from Family Genetic Risk Scores. Poor social outcome was defined by a common factor of four variables: receipt of social welfare, sick leave, early retirement pension, and residence in a socially deprived area. Psychiatric outcome was defined as days of inpatient psychiatric hospitalization.</p><p><strong>Results: </strong>With poorer social outcomes, the primary genetic risks rose robustly for all disorders except SZ, as did the secondary genetic risks for DUD, AUD, and attention-deficit hyperactivity disorder. With poorer psychiatric outcomes, available only for BD and SZ, the primary genetic risks increased sharply. Overall, MD, AD, and BD became substantially more genetically heterogenous as their social outcomes became poorer, while for AUD, DUD, and SZ, the increase in heterogeneity was more modest. By contrast, with poorer psychiatric outcome, genetic risks for SZ became substantially more genetically homogeneous, with a similar but less robust trend seen for BD.</p><p><strong>Conclusions: </strong>Despite important differences between our primary disorders, social and psychiatric outcomes are often robust indices of genetic risk and can reflect the levels of genetic heterogeneity.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":"55 ","pages":"e233"},"PeriodicalIF":5.5,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12360690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144856138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}