JAMA Psychiatry最新文献

{"title":"Modifying Informed Consent to Help Address Functional Unmasking in Psychedelic Clinical Trials","authors":"Michelle Matvey, D. Parker Kelley, Ellen R. Bradley, Winston Chiong, Aoife O’Donovan, Josh Woolley","doi":"10.1001/jamapsychiatry.2024.4312","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.4312","url":null,"abstract":"ImportanceThere is unprecedented clinician, industry, and patient interest in the therapeutic development of psychedelic drugs. This is due to a combination of promising clinical trial results, positive media coverage, and the lack of novel pharmacologic treatments for psychiatric disorders in recent decades. However, the field faces a key methodological challenge: masking participants to treatment conditions in psychedelic clinical trials has been largely unsuccessful.ObjectiveWhen participants can tell whether they received active drug or placebo, their responses to clinical assessments, questionnaires, and even their functional imaging and biological data can be influenced by preconceptions about treatment effects. Positive patient expectancies combined with ineffective masking may skew outcomes and inflate effect sizes. This complicates efforts to determine the safety and efficacy of psychedelic drugs. Here, we explore a method to help address this problem: modifying informed consent to obscure information about the study design.Evidence ReviewWe reviewed all contemporary (2000-2024) clinical trials of psychedelic or methylenedioxymethamphetamine (MDMA) therapy and corresponded with the investigators to compile information on the use of modifications to informed consent in these studies.FindingsModifying informed consent to obscure details of the study design has been implemented in several psychedelic clinical trials and may offer a way to strengthen masking. However, this approach poses significant ethical risks. We examine examples of modifications used in the psychedelic literature, discuss the current regulatory landscape, and suggest strategies to mitigate risks associated with modified informed consent.Conclusions and RelevanceIncorporating modified informed consent in future psychedelic clinical trials may improve interpretability and impact, but this has not been explicitly tested. Modifications to informed consent may not be appropriate in all cases, and risks to participants should be minimized by implementing appropriate guardrails.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"82 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936339","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":"Genetic Analysis of Retinal Cell Types in Neuropsychiatric Disorders","authors":"Emanuel Boudriot, Marius Stephan, Finn Rabe, Lukasz Smigielski, Andrea Schmitt, Peter Falkai, Michael J. Ziller, Moritz J. Rossner, Philipp Homan, Sergi Papiol, Florian J. Raabe","doi":"10.1001/jamapsychiatry.2024.4230","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.4230","url":null,"abstract":"ImportanceAs an accessible part of the central nervous system, the retina provides a unique window to study pathophysiological mechanisms of brain disorders in humans. Imaging and electrophysiological studies have revealed retinal alterations across several neuropsychiatric and neurological disorders, but it remains largely unclear which specific cell types and biological mechanisms are involved.ObjectiveTo determine whether specific retinal cell types are affected by genomic risk for neuropsychiatric and neurological disorders and to explore the mechanisms through which genomic risk converges in these cell types.Design, Setting, and ParticipantsThis genetic association study combined findings from genome-wide association studies in schizophrenia, bipolar disorder, major depressive disorder, multiple sclerosis, Parkinson disease, Alzheimer disease, and stroke with retinal single-cell transcriptomic datasets from humans, macaques, and mice. To identify susceptible cell types, Multi-Marker Analysis of Genomic Annotation (MAGMA) cell-type enrichment analyses were applied and subsequent pathway analyses performed. The cellular top hits were translated to the structural level using retinal optical coherence tomography (acquired between 2009 and 2010) and genotyping data in the large population-based UK Biobank cohort study. Data analysis was conducted between 2022 and 2024.Main Outcomes and MeasuresCell type–specific enrichment of genetic risk loading for neuropsychiatric and neurological disorder traits in the gene expression profiles of retinal cells.ResultsExpression profiles of amacrine cells (interneurons within the retina) were robustly enriched in schizophrenia genetic risk across mammalian species and in different developmental stages. This enrichment was primarily driven by genes involved in synapse biology. Moreover, expression profiles of retinal immune cell populations were enriched in multiple sclerosis genetic risk. No consistent cell-type associations were found for bipolar disorder, major depressive disorder, Parkinson disease, Alzheimer disease, or stroke. On the structural level, higher polygenic risk for schizophrenia was associated with thinning of the ganglion cell inner plexiform layer, which contains dendrites and synaptic connections of amacrine cells (B, −0.09; 95% CI, −0.16 to −0.03; <jats:italic>P</jats:italic> = .007; n = 36 349; mean [SD] age, 57.50 [8.00] years; 19 859 female [54.63%]). Higher polygenic risk for multiple sclerosis was associated with increased thickness of the retinal nerve fiber layer (B, 0.06; 95% CI, 0.02 to 0.10; <jats:italic>P</jats:italic> = .007; n = 36 371; mean [SD] age, 57.51 [8.00] years; 19 843 female [54.56%]).Conclusions and RelevanceThis study provides novel insights into the cellular underpinnings of retinal alterations in neuropsychiatric and neurological disorders and highlights the retina as a potential proxy to study synaptic pathology in schizophrenia.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"56 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936193","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":"Deconstructing Cognitive Impairment in Psychosis With a Machine Learning Approach.","authors":"Robert A McCutcheon, Richard S E Keefe, Philip M McGuire, Andre Marquand","doi":"10.1001/jamapsychiatry.2024.3062","DOIUrl":"10.1001/jamapsychiatry.2024.3062","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Cognitive functioning is associated with various factors, such as age, sex, education, and childhood adversity, and is impaired in people with psychosis. In addition to specific effects of the disorder, cognitive impairments may reflect a greater exposure to general risk factors for poor cognition.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To determine the extent that impairments in cognition in psychosis reflect risk factor exposures.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design, setting, and participants: &lt;/strong&gt;This cross-sectional study examined the relationship between exposures and cognitive function using data from the Bipolar-Schizophrenia Network on Intermediate Phenotypes studies 1 and 2 across 6 sites. Participants included healthy controls; patients with schizophrenia, schizoaffective disorder, or bipolar I disorder with psychosis; and relatives of patients. Predictive modeling was performed using extreme gradient boosting regression to train a composite cognitive score prediction model with nested cross-validation. Shapley additive explanations values were used to examine the relationship between exposures and cognitive function.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Exposure: &lt;/strong&gt;Exposures were chosen based on associations with cognition previously identified: age, sex, race and ethnicity, childhood adversity, education, parental education, parental socioeconomic status, parental age at birth, substance use, antipsychotic dose, and diagnosis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcomes and measures: &lt;/strong&gt;Cognition was assessed using the Brief Assessment of Cognition in Schizophrenia.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 3370 participants were included: 840 healthy controls, 709 patients with schizophrenia, 541 with schizoaffective disorder, 457 with bipolar I disorder with psychosis, and 823 relatives of patients. The mean (SD) age was 37.9 (13.3) years; 1887 were female (56%) and 1483 male (44%). The model predicted cognitive scores with high accuracy: out-of-sample Pearson correlation between predicted and observed cognitive composite score was r = 0.72 (SD = 0.03). Individuals with schizophrenia (z = -1.4), schizoaffective disorder (z = -1.2), and bipolar I disorder with psychosis (z = -0.5) all had significantly worse cognitive composite scores than controls. Factors other than diagnosis and medication accounted for much of this impairment (schizophrenia z = -0.73, schizoaffective disorder z = -0.64, bipolar I disorder with psychosis z = -0.13). Diagnosis accounted for a lesser proportion of this deficit (schizophrenia z = -0.29, schizoaffective disorder z = -0.15, bipolar I disorder with psychosis z = -0.13), and antipsychotic use accounted for a similar deficit across diagnostic groups (schizophrenia z = -0.37, schizoaffective disorder z = -0.33, bipolar I disorder with psychosis z = -0.26).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions and relevance: &lt;/strong&gt;This study found that transdiagnostic factors accounted for a meaningful share of the variance in cognitive fu","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":"57-65"},"PeriodicalIF":22.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11465119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Racial and Ethnic Disparities in Fentanyl and Polysubstance Overdose Deaths.","authors":"David T Zhu","doi":"10.1001/jamapsychiatry.2024.3435","DOIUrl":"10.1001/jamapsychiatry.2024.3435","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":"99-100"},"PeriodicalIF":22.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11581714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ending Unequal Treatment for People With Behavioral Health Conditions.","authors":"Ruth S Shim, Margarita Alegría","doi":"10.1001/jamapsychiatry.2024.3596","DOIUrl":"10.1001/jamapsychiatry.2024.3596","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":"10-11"},"PeriodicalIF":22.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675868","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":"Slowing Cognitive Decline in Major Depressive Disorder and Mild Cognitive Impairment: A Randomized Clinical Trial.","authors":"Tarek K Rajji, Christopher R Bowie, Nathan Herrmann, Bruce G Pollock, Krista L Lanctôt, Sanjeev Kumar, Alastair J Flint, Linda Mah, Corinne E Fischer, Meryl A Butters, Marom Bikson, James L Kennedy, Daniel M Blumberger, Zafiris J Daskalakis, Damien Gallagher, Mark J Rapoport, Nicolaas P L G Paul Verhoeff, Angela C Golas, Ariel Graff-Guerrero, Erica Vieira, Aristotle N Voineskos, Heather Brooks, Ashley Melichercik, Kevin E Thorpe, Benoit H Mulsant","doi":"10.1001/jamapsychiatry.2024.3241","DOIUrl":"10.1001/jamapsychiatry.2024.3241","url":null,"abstract":"<p><strong>Importance: </strong>Older adults with major depressive disorder (MDD) or mild cognitive impairment (MCI) are at high risk for cognitive decline.</p><p><strong>Objective: </strong>To assess the efficacy of cognitive remediation (CR) plus transcranial direct current stimulation (tDCS) targeting the prefrontal cortex in slowing cognitive decline, acutely improving cognition, and reducing progression to MCI or dementia in older adults with remitted MDD (rMDD), MCI, or both.</p><p><strong>Design, setting, and participants: </strong>This randomized clinical trial was conducted at 5 academic hospitals in Toronto, Ontario, Canada. Participants were older adults who had rMDD (with or without MCI, age ≥65 y) or MCI without rMDD (age ≥60 y). Assessments were made at baseline, month 2, and yearly from baseline for 3 to 7 years.</p><p><strong>Interventions: </strong>CR plus tDCS (hereafter, active) or sham plus sham 5 days a week for 8 weeks followed by twice-a-year 5-day boosters and daily at-home CR or sham CR.</p><p><strong>Main outcomes and measures: </strong>The primary outcome was change in global composite cognitive score. Secondary outcomes included changes in 6 cognitive domains, moderating effect of the diagnosis, moderating effect of APOE ε4 status, change in composite score at month 2, and progression to MCI or dementia over time.</p><p><strong>Results: </strong>Of 486 older adults who provided consent, 375 (with rMDD, MCI, or both) received at least 1 intervention session (mean [SD] age, 72.2 [6.4] years; 232 women [62%] and 143 men [38%]). Over a median follow-up of 48.3 months (range, 2.1-85.9), CR and tDCS slowed cognitive decline in older adults with rMDD or MCI (adjusted z score difference [active - sham] at month 60, 0.21; 95% CI, 0.07 to 0.35; likelihood ratio test [LRT] P = .006). In the preplanned primary analysis, CR and tDCS did not improve cognition acutely (adjusted z score difference [active - sham] at month 2, 0.06, 95% CI, -0.006 to 0.12). Similarly, the effect of CR and tDCS on delaying progression from normal cognition to MCI or MCI to dementia was weak and not significant (hazard ratio, 0.66; 95% CI, 0.40 to 1.08; P = .10). Preplanned analyses showed treatment effects for executive function (LRT P = .04) and verbal memory (LRT P = .02) and interactions with diagnosis (P = .01) and APOE ε4 (P < .001) demonstrating a larger effect among those with rMDD and in noncarriers of APOE ε4.</p><p><strong>Conclusions and relevance: </strong>The study showed that CR and tDCS, both targeting the prefrontal cortex, is efficacious in slowing cognitive decline in older adults at risk of cognitive decline, particularly those with rMDD (with or without MCI) and in those at low genetic risk for Alzheimer disease.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT02386670.</p>","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":"12-21"},"PeriodicalIF":22.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11525663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TikTok Challenges-Unintentional Injuries vs Suicide Attempts.","authors":"Onomeasike Ataga, Valerie K Arnold","doi":"10.1001/jamapsychiatry.2024.3522","DOIUrl":"10.1001/jamapsychiatry.2024.3522","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":"5-6"},"PeriodicalIF":22.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582778","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":"Sexual Trauma, Polygenic Scores, and Mental Health Diagnoses and Outcomes.","authors":"Allison M Lake, Yu Zhou, Bo Wang, Ky'Era V Actkins, Yingzhe Zhang, John P Shelley, Anindita Rajamani, Michael Steigman, Chris J Kennedy, Jordan W Smoller, Karmel W Choi, Nikhil K Khankari, Lea K Davis","doi":"10.1001/jamapsychiatry.2024.3426","DOIUrl":"10.1001/jamapsychiatry.2024.3426","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Leveraging real-world clinical biobanks to investigate the associations between genetic and environmental risk factors for mental illness may help direct clinical screening efforts and evaluate the portability of polygenic scores across environmental contexts.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To examine the associations between sexual trauma, polygenic liability to mental health outcomes, and clinical diagnoses of schizophrenia, bipolar disorder, and major depressive disorder in a clinical biobank setting.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design, setting, and participants: &lt;/strong&gt;This genetic association study was conducted using clinical and genotyping data from 96 002 participants across hospital-linked biobanks located at Vanderbilt University Medical Center (VUMC), Nashville, Tennessee (including 58 262 individuals with high genetic similarity to the 1000 Genomes Project [1KG] Northern European from Utah reference population [1KG-EU-clustered] and 11 047 with high genetic similarity to the 1KG African-ancestry reference population of Yoruba in Ibadan, Nigeria [1KG-YRI-clustered]), and Mass General Brigham (MGB), Boston, Massachusetts (26 693 individuals with high genetic similarity to the combined European-ancestry superpopulation [1KG-EU-clustered]). Clinical data analyzed included diagnostic billing codes and clinical notes spanning from 1976 to 2023. Data analysis was performed from 2022 to 2024.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Exposures: &lt;/strong&gt;Clinically documented sexual trauma disclosures and polygenic scores for schizophrenia, bipolar disorder, and major depressive disorder.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcomes and measures: &lt;/strong&gt;Diagnoses of schizophrenia, bipolar disorder, and major depressive disorder, determined by aggregating related diagnostic billing codes, were the dependent variables in logistic regression models including sexual trauma disclosure status, polygenic scores, and their interactions as the independent variables.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Across the VUMC and MGB biobanks, 96 002 individuals were included in analyses (VUMC 1KG-EU-clustered: 33 011 [56.7%] female; median [range] age, 56.8 [10.0 to &gt;89] years; MGB 1KG-EU-clustered: 14 647 [54.9%] female; median [range] age, 58.0 [10.0 to &gt;89] years; VUMC 1KG-YRI-clustered: 6961 [63.0%] female; median [range] age, 44.6 [10.1 to &gt;89] years). Sexual trauma history was associated with all mental health conditions across institutions (ORs ranged from 8.83 [95% CI, 5.50-14.18] for schizophrenia in the VUMC 1KG-YRI-clustered cohort to 17.65 [95% CI, 12.77-24.40] for schizophrenia in the VUMC 1KG-EU-clustered cohort). Sexual trauma history and polygenic scores jointly explained 3.8% to 8.8% of mental health phenotypic variance. Schizophrenia and bipolar disorder polygenic scores had greater associations with mental health outcomes in individuals with no documented disclosures of sexual trauma (schizophrenia interaction: OR, 0.70 [95% CI, 0.56-0.88]; bipolar disorder interac","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":"75-84"},"PeriodicalIF":22.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11581726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Building Resilient Relationships.","authors":"Manasi Kumar, Jennifer Mootz, Myrna Weissman","doi":"10.1001/jamapsychiatry.2024.3400","DOIUrl":"10.1001/jamapsychiatry.2024.3400","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":"6-8"},"PeriodicalIF":22.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545623","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":"A Group Parenting Intervention for Male Postpartum Depression: A Cluster Randomized Clinical Trial.","authors":"M Ishrat Husain, Tayyeba Kiran, Rabia Sattar, Ameer B Khoso, Ming Wai Wan, Daisy R Singla, Madeha Umer, Rabdino Mangrio, Paul Bassett, Imran B Chaudhry, Shehla N Zafar, Farhat A Jafri, Nasim Chaudhry, Nusrat Husain","doi":"10.1001/jamapsychiatry.2024.2752","DOIUrl":"10.1001/jamapsychiatry.2024.2752","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Male postpartum depression is prevalent across populations; however, there is limited evidence on strategies to address it, particularly in low-income settings.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To evaluate the effectiveness of Learning Through Play Plus Dads (LTP + Dads), a nonspecialist-delivered psychosocial intervention, in improving symptoms of male postpartum depression compared to treatment as usual.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design, setting, and participants: &lt;/strong&gt;This cluster randomized clinical trial was conducted in Karachi, Pakistan, between June 2018 and November 2019. Assessors were blind to treatment allocation. Participants were recruited from 2 large towns in the city of Karachi via basic health units. Fathers aged 18 years and older with a DSM-5 diagnosis of major depressive episode and a child younger than 30 months were recruited. Of 1582 fathers approached, 1527 were screened and 357 were randomized in a 1:1 ratio to either the intervention or treatment as usual; 328 were included in the final analysis. Data were analyzed from April to June 2022.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interventions: &lt;/strong&gt;LTP + Dads is a manualized intervention combining parenting skills training, play therapy, and cognitive behavior therapy. The intervention was delivered by community health workers via 12 group sessions over 4 months.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcomes and measures: &lt;/strong&gt;The primary outcome was change in 17-item Hamilton Depression Rating Scale score at 4 months. Secondary outcomes included anxiety symptoms; parenting stress; intimate partner violence; functioning; quality of life; and child social, emotional, and physical health outcomes. Assessments were completed at baseline and 4 and 6 months postrandomization.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Of the 357 fathers included (mean [SD] age, 31.44 [7.24] years), 171 were randomized to the intervention and 186 to treatment as usual. Participants randomized to the intervention demonstrated significantly greater improvements in depression (group difference ratio [GDR], 0.66; 95% CI, 0.47 to 0.91; P &lt; .001), anxiety (GDR, 0.62; 95% CI, 0.48 to 0.81; P &lt; .001), parenting stress (GDR, -12.5; 95% CI, -19.1 to -6.0; P &lt; .001), intimate partner violence (GDR, 0.89; 95% CI, 0.80 to 1.00; P = .05), disability (GDR, 0.77; 95% CI, 0.61 to 0.97; P = .03), and health-related quality of life (GDR, 12.7; 95% CI, 0.17 to 0.34; P &lt; .001) at 4 months. The difference in depression and parenting stress was sustained at 6 months. Children of fathers randomized to the parenting intervention had significantly greater improvements in social-emotional development scores (mean difference, -20.8; 95% CI, -28.8 to -12.9; P &lt; .001) at 6 months.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions and relevance: &lt;/strong&gt;The psychosocial parenting intervention in this study has the potential to improve paternal mental health and child development in Pakistan. Further studies in other populations and with longer follow-up are warranted","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":"22-30"},"PeriodicalIF":22.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}