JAMA Psychiatry最新文献

{"title":"Cannabis Withdrawal and Psychiatric Intensive Care.","authors":"Aliyah Malik, Hitesh Shetty, Dominic Oliver, Thomas J Reilly, Marta Di Forti, Philip McGuire, Edward Chesney","doi":"10.1001/jamapsychiatry.2025.1216","DOIUrl":"10.1001/jamapsychiatry.2025.1216","url":null,"abstract":"<p><strong>Importance: </strong>Cannabis use is common in people with severe mental illness and its adverse effects on outcomes are well established. However, adverse outcomes may also result from cannabis withdrawal syndrome (CWS). CWS includes symptoms such as agitation, irritability, and aggression, and typically peaks after 3 to 5 days of abstinence.</p><p><strong>Objective: </strong>To assess whether cannabis use prior to admission is associated with an increase in the risk of transfer to a psychiatric intensive care unit (PICU) during the cannabis withdrawal risk period.</p><p><strong>Design, setting, and participants: </strong>This retrospective cohort study used clinical data from a secondary mental health care database and took place at 4 psychiatric hospitals in London, United Kingdom, between January 2008 and December 2023. Patients included adults admitted to general psychiatric wards and PICUs. Data were analyzed from June 2023 to February 2025.</p><p><strong>Exposure: </strong>Cannabis use was determined from clinical records, using natural language processing and manual review.</p><p><strong>Main outcomes and measures: </strong>The primary outcome was transfer from a general ward to PICU during the cannabis withdrawal risk period (3 to 5 days after presentation to the hospital). Secondary outcomes included admission to PICU at any time point. Outcomes were analyzed according to cannabis use status with multivariable models, which adjusted for age, gender, ethnicity, diagnosis, tobacco use, stimulant use, comorbid alcohol or substance use disorder, and admission year.</p><p><strong>Results: </strong>There were 52 088 hospital admissions identified, of which 4691 involved admission to a PICU (9.0%). Cannabis users were more likely to be admitted to a PICU than nonusers (adjusted odds ratio [aOR], 1.44; 95% CI, 1.33-1.55; P < .001). There were 1236 admissions where the patient was transferred to PICU after initial admission to a general ward (mean [SD] age, 33.4 [10.4] years; 810 male [66%] and 426 female [34%]). At 3 to 5 days postpresentation (the risk period for cannabis withdrawal), transfer from a general ward to a PICU was more common in cannabis users (31.0%) than nonusers (24.2%) (aOR, 1.36; 95% CI, 1.01-1.81; P = .04). The association was particularly evident in women (aOR, 2.03; 95% CI, 1.22-3.39; P = .007) and in those older than 35 years (aOR, 2.53; 95%CI: 1.52-4.21; P < .001).</p><p><strong>Conclusions and relevance: </strong>People with severe mental illness who are cannabis users may develop cannabis withdrawal syndrome shortly after hospital admission, and this can exacerbate their mental state.</p>","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":"838-843"},"PeriodicalIF":17.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266285","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":"Symptom Provocation and Clinical Response to Transcranial Magnetic Stimulation: A Systematic Review and Meta-Analysis.","authors":"Daniel Bello, Megan Jones, Ishaan Gadiyar, Laura Artim, Sophia H Blyth, Roscoe O Brady, Simon Vandekar, Heather Burrell Ward","doi":"10.1001/jamapsychiatry.2025.0792","DOIUrl":"10.1001/jamapsychiatry.2025.0792","url":null,"abstract":"<p><strong>Importance: </strong>Transcranial magnetic stimulation (TMS), a form of noninvasive brain stimulation used to treat major depressive disorder, obsessive-compulsive disorder (OCD), and nicotine dependence, has well-established state-dependent effects on brain circuitry. However, a major question for TMS remains: does brain state affect clinical response?</p><p><strong>Objective: </strong>To quantify the association between symptom provocation and clinical response to TMS for OCD and nicotine dependence, the only Food and Drug Administration-cleared TMS indications with symptom provocation.</p><p><strong>Data sources: </strong>PubMed, CINAHL, Embase, PsycInfo until August 30, 2024.</p><p><strong>Study selection: </strong>Randomized clinical trials of TMS for OCD or nicotine dependence with a clinical outcome. Of 600 studies identified, 71 met inclusion criteria.</p><p><strong>Data extraction and synthesis: </strong>Data extraction was completed independently by 2 extractors and cross-checked by a third. Standardized mean difference (SMD) and SE were estimated via Hedges g and synthesized data in a 3-level random-effects meta-analysis. Study data were analyzed from August 2023 to March 2025.</p><p><strong>Main outcomes and measures: </strong>Primary outcomes were clinical response measures.</p><p><strong>Results: </strong>A total of 71 studies met inclusion criteria and included 3246 participants (mean [SD] age; 37.8 [8.0] years; mean [SD] percentage female, 44.1% [17.2%]). Included in the meta-analysis were 63 studies with 2998 participants. For OCD studies, active TMS was associated with better clinical response than sham both with (SMD = -0.51; 95% CI, -0.96 to -0.07; P = 0.04) and without (SMD = -0.29; 95% CI, -0.40 to -0.17; P < .001) symptom provocation. For nicotine use, active TMS was associated with better clinical response than sham when used with (SMD = -0.56; 95% CI, -1.12 to 0; P = .05) but not without (SMD = -0.35; 95% CI, -0.74 to 0.04; P = .08) symptom provocation. For OCD studies, the estimated expected added effect of provocation was SMD of -0.22 (95% CI, -0.65 to 0.20; P = .22). In nicotine studies, the estimated expected added effect of provocation was SMD of -0.21 (95% CI, -1.00 to 0.58; P = .57).</p><p><strong>Conclusions and relevance: </strong>Results of this systematic review and meta-analysis suggest that symptom provocation may enhance clinical response to TMS for OCD and nicotine dependence. Studies comparing TMS with and without provocation are critical to establish the causal effect of provocation.</p>","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":"768-777"},"PeriodicalIF":17.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12138803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215891","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":"Simvastatin as Add-On Treatment to Escitalopram in Patients With Major Depression and Obesity: A Randomized Clinical Trial.","authors":"Christian Otte, Woo Ri Chae, Deniz Yildirim Dogan, Dominique Piber, Stefan Roepke, An Bin Cho, Samuel Trumm, Michael Kaczmarczyk, Jelena Brasanac, Katja Wingenfeld, Stefanie Koglin, Johannes Wieditz, Klaus Junghanns, Michael Lucht, David Prvulovic, Tillmann H C Krüger, Jan Terock, Moritz Haaf, Tobias Hofmann, Nicole Mauche, Jan Philipp Klein, Hans Jörgen Grabe, Andreas Reif, Kai G Kahl, Deborah Janowitz, Gregor Leicht, Kim Hinkelmann, Maria Strauß, Tim Friede, Stefan M Gold","doi":"10.1001/jamapsychiatry.2025.0801","DOIUrl":"10.1001/jamapsychiatry.2025.0801","url":null,"abstract":"<p><strong>Importance: </strong>Major depressive disorder (MDD) and obesity are common noncommunicable disorders associated with substantial disease burden, which frequently occur comorbidly. Intriguingly, converging lines of evidence from animal models and genetic and observational studies have suggested a biological link between obesity, metabolic syndrome, and depression. Several small randomized clinical trials (RCTs) have suggested the antidepressive potential of statins.</p><p><strong>Objective: </strong>To examine whether simvastatin added to escitalopram is efficacious in improving depressive symptoms compared with add-on placebo.</p><p><strong>Design, setting, and participants: </strong>This was a confirmatory, double-blind, placebo-controlled, multicenter RCT. Adults with MDD and comorbid obesity from 9 tertiary care settings in Germany were enrolled in this analysis. Data were analyzed from July to October 2024.</p><p><strong>Interventions: </strong>Simvastatin (40 mg per day) or placebo as add-on to escitalopram (10 mg for the first 2 weeks, then increased to 20 mg until the end of study) in a double-blind fashion for 12 weeks.</p><p><strong>Main outcomes and measures: </strong>The primary outcome was change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline (week 0) to week 12.</p><p><strong>Results: </strong>From August 21, 2020, to June 06, 2024, a total of 161 patients were enrolled at 9 sites in Germany, of which 160 patients were included in the intention-to-treat analysis (placebo: n = 79, simvastatin: n = 81; mean [SD] age, 39.0 [11.0] years; 126 female [79%]). Retention in the trial was excellent (95.6%), and blinding was effectively maintained. There were 4 serious adverse events with no difference between the groups. Primary end point analysis in the intention-to-treat sample showed no significant treatment effect of add-on simvastatin in MADRS scores (mixed models for repeated measures least squares mean difference, 0.47 points; 95% CI, -2.08 to 3.02; P = .71). No effects of simvastatin treatment were observed in any of the mental health-related secondary end points. However, simvastatin treatment significantly reduced low-density lipoprotein cholesterol (simvastatin, -40.37 mg/dL; 95% CI, -47.41 to -33.33 mg/dL; placebo, -3.78 mg/dL; 95% CI, -11.18 to 3.62 mg/dL; P < .001), total cholesterol (simvastatin, -39.07 mg/dL; 95% CI, -49.42 to -28.73 mg/dL; placebo, -4.89 mg/dL; 95% CI, -15.64 to 5.87 mg/dL; P < .001), and C-reactive protein (simvastatin, -1.04 mg/L; 95% CI, -1.89 to -0.20 mg/L; placebo, 0.57 mg/L; 95% CI, -0.28 to 1.42 mg/L; P = .003) compared with placebo.</p><p><strong>Conclusions and relevance: </strong>The study failed to meet its primary end point. This demonstrates that simvastatin did not exert additional antidepressive effects when added to escitalopram in patients with comorbid MDD and obesity, despite improving the cardiovascular risk profile.</p><p><strong>Trial registration: </","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":"759-767"},"PeriodicalIF":17.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12138799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215890","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":"Esketamine Combined With SSRI or SNRI for Treatment-Resistant Depression.","authors":"Antonio Del Casale, Sara Spirito, Jan Francesco Arena, Saskia Preissner, Marina Borro, Giovanna Gentile, Martina Nicole Modesti, Robert Preissner, Stefano Ferracuti, Maurizio Simmaco","doi":"10.1001/jamapsychiatry.2025.0200","DOIUrl":"10.1001/jamapsychiatry.2025.0200","url":null,"abstract":"<p><strong>Importance: </strong>Treatment-resistant depression (TRD) remains a critical challenge in psychiatry, with limited effective options. Esketamine, a rapid-acting antidepressant, is usually combined with a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI), but comparative evidence of these combinations' effectiveness in real-world settings is sparse.</p><p><strong>Objective: </strong>To determine whether the combination of esketamine + SNRI shows differences in clinical outcomes compared to esketamine + SSRI in patients with TRD.</p><p><strong>Design, setting, and participants: </strong>This retrospective cohort study was conducted in September 2024 using data from the TriNetX global health research network, with a 5-year time window from the first esketamine trial. TriNetX data are drawn from real-world clinical settings and use electronic medical records from more than 90 health care centers across 20 countries. Adults with TRD who were treated with esketamine combined with either an SSRI or an SNRI were eligible for inclusion.</p><p><strong>Exposure: </strong>Treatment with esketamine combined with an SSRI (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, or vilazodone) or an SNRI (desvenlafaxine, duloxetine, levomilnacipran, milnacipran, or venlafaxine).</p><p><strong>Main outcomes and measures: </strong>The primary outcomes were all-cause mortality, hospitalization, depression relapse, and suicide attempts. Kaplan-Meier survival analysis was used to estimate survival probabilities, while risk ratios and odds ratios were calculated for all outcomes.</p><p><strong>Results: </strong>In a population-based sample of 61 882 adult participants with TRD who were treated with esketamine combined with either an SSRI or an SNRI, 55 480 participants were selected after applying propensity score matching for age and sex. These patients were divided into 2 matched cohorts: 27 740 patients treated with esketamine + SSRI (16 007 female participants [57.7%]; mean [SD] age, 46.0 [21.3] years) and 27 740 treated with esketamine + SNRI (16 242 female participants [58.6%]; mean [SD] age, 45.9 [21.9] years). In the entire study population, the incidence of mortality, hospitalizations, depressive relapses, and suicide attempts was low throughout the study period. Patients in the esketamine + SNRI group had significantly lower all-cause mortality (5.3% vs 9.1%; P < .001), hospitalization rates (0.1% vs 0.2%; P < .001), and depression relapses (14.8% vs 21.2%; P < .001) compared to the esketamine + SSRI group, which instead showed a lower incidence of suicidal attempts (0.3% vs 0.5%; P = .04).</p><p><strong>Conclusions and relevance: </strong>In this retrospective comparative effectiveness study, among the study sample, incidence of mortality, hospitalizations, depressive relapses, and suicide attempts was low. The esketamine + SNRI group showed lower incidence of mortality, hospi","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":"810-817"},"PeriodicalIF":17.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11966478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763973","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":"Brain Organoids in the Study of Psychiatric Disorders.","authors":"Yukyeong Lee,Paul K Reardon,Rakesh Karmacharya","doi":"10.1001/jamapsychiatry.2025.1869","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.1869","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"54 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144748019","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":"Pain Reprocessing Therapy vs Placebo and Usual Care for Patients With Chronic Back Pain","authors":"Yoni K. Ashar, Ethan L. Low, Karen Knight, Howard Schubiner, Alan Gordon, Andrew LeRoux, Mark A. Lumley, Tor D. Wager","doi":"10.1001/jamapsychiatry.2025.1844","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.1844","url":null,"abstract":"This secondary analysis of a randomized clinical trial provided 5-year follow-up data for individuals with chronic back pain treated with pain reprocessing therapy, placebo, or usual care.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"26 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144737728","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":"Risk Factors for Catatonia Relapse in Psychotic and Affective Disorders","authors":"Harsh Pathak, Sneha Susan Varghese, Satish Suhas, Durai Murukan Gunasekaran, Guru S. Gowda, Krishna Prasad Muliyala, Venkata Senthil Kumar Reddi","doi":"10.1001/jamapsychiatry.2025.1818","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.1818","url":null,"abstract":"ImportanceCatatonia is a recurrent syndrome, yet the risk factors associated with its long-term course and relapse remain poorly understood. This study yields insights into the time to relapse in catatonia. It also characterizes the demographic, clinical, and treatment-related factors associated with relapse across psychotic and affective spectrum disorders.ObjectiveTo examine the relapse rate of catatonia and identify factors associated with relapse, particularly in patients with psychotic and affective spectrum disorders, over an extended follow-up period.Design, Setting, and ParticipantsThis retrospective cohort study was conducted at a tertiary neuropsychiatric center in India. Patients who presented with catatonia to emergency psychiatry and acute care services between January 2014 and December 2017 were included. Follow-up was up to 78 months, with the final follow-up completed in December 2020. Data were analyzed in November 2024.ExposuresCatatonia in psychotic or affective spectrum disorders.Main Outcomes and MeasuresThe primary outcome was catatonia relapse defined as the recurrence of catatonic symptoms during follow-up. Survival analysis included Kaplan-Meier curves, log-rank tests, and Cox proportional hazards regression to assess time to relapse and identify factors associated with relapse risk.ResultsOf 303 patients with catatonia included in the analysis, relapse occurred in 148 (48.8%; mean [SD] age, 30.09 [9.54] years; 80 females [60.7%]; 94 [63.5%] with psychotic spectrum disorder) over a median (IQR) follow-up of 29.8 (10.8-47.0) months, while 155 patients (55.2%; mean [SD] age, 31.27 [11.80] years; 93 females [60.0%]; 97 [62.6%] with psychotic spectrum disorder) had no relapse. Relapse risk was highest within 2 years of an index episode. Antipsychotic prescriptions at discharge were associated with longer times to relapse and a relapse risk reduction of 41.1% (hazard ratio, 0.59; 95% CI, 0.38-0.92; <jats:italic>P</jats:italic> = .02). The underlying psychiatric diagnosis (psychotic vs affective spectrum disorder) was not associated with relapse rates or time to relapse.Conclusions and RelevanceCatatonia is a recurrent condition, with nearly half of patients experiencing relapses, particularly within the first 2 years. Antipsychotic treatment may play a crucial role in relapse prevention, emphasizing the need for maintenance therapy during this critical period. While preliminary, these findings highlight the importance of evolving long-term management strategies to prevent catatonia relapse and call for further research into the pathophysiological mechanisms underlying catatonia.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"13 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144737667","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":"Mental Health Research in the Department of Veterans Affairs.","authors":"Mark A Reger,Miriam J Smyth","doi":"10.1001/jamapsychiatry.2025.1808","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.1808","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"7 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684385","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":"Omitted Disclosures.","authors":"","doi":"10.1001/jamapsychiatry.2025.2398","DOIUrl":"10.1001/jamapsychiatry.2025.2398","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":""},"PeriodicalIF":17.1,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12284805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690292","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":"Inflammatory Exposure and Depression in Older Adults With Insomnia: A Randomized Clinical Trial.","authors":"Michael R Irwin,Chloe C Boyle,Joshua H Cho,Dominique Piber,Nina Sadeghi,Daisy Castillo,Michael T Smith,Naomi I Eisenberger,Richard Olmstead","doi":"10.1001/jamapsychiatry.2025.1327","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.1327","url":null,"abstract":"ImportanceInsomnia and inflammation are prevalent in older adults, and both are risk factors for late-life depression. Older adults with insomnia who are exposed to inflammatory challenge may be more vulnerable to depression.ObjectiveTo determine whether inflammatory exposure induces greater increases in depressive mood and symptoms in older adults with insomnia disorder compared to those without insomnia.Design, Setting, and ParticipantsThis assessor-blinded, parallel-condition randomized clinical trial was conducted from August 2017 to November 2022 at a single site in Los Angeles, California, among a community-based sample of 160 nondepressed adults aged 60 years or older (53 with insomnia disorder and 107 without insomnia, or control). Data analysis occurred from July 2023 to August 2024.InterventionsParticipant groups stratified by insomnia status were randomized to 2 conditions: endotoxin or placebo.Main Outcomes and MeasuresThe primary outcome was depressed mood, assessed by the Profiles of Mood States depression subscale (POMS-D). Secondary outcomes were depressive symptom severity and inflammatory cytokines.ResultsAmong 160 randomized participants eligible for the study (mean [SD] age, 65.9 [4.6] years; 84 female participants [52.5%]), 79 participants (26 with insomnia, 53 control participants) were randomized to endotoxin and 81 (27 with insomnia, 54 control participants) to placebo. All randomized participants completed the protocol. Compared to placebo, endotoxin induced increases in POMS-D to a significantly greater extent in those with insomnia than controls (condition × group interaction, F10,1478 = 4.7; P < .001), with a similar effect for observer-rated POMS-D mood (condition × group interaction, F3,450 = 5.5; P = .001), as well as clinically meaningful increases in observer-rated measures of depressive symptoms. Endotoxin induced similar increases in inflammatory cytokines in both groups. Moderation analyses found that the inflammatory response was associated with increases in POMS-D in the insomnia group (β = 0.33; 95% CI, 0.26-0.41; P < .001) but not in control participants.Conclusions and RelevanceIn this randomized clinical trial, older adults with insomnia showed an exaggerated vulnerability to depressive mood and symptoms in response to inflammatory challenge. Older adults with insomnia should undergo vigilant depression monitoring during periods of inflammatory exposure; selective depression prevention strategies that target both insomnia and inflammatory phenotypes are needed.Trial RegistrationClinicalTrials.gov Identifier: NCT03256760.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"24 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640154","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}