JAMA Psychiatry最新文献

{"title":"Mental Health Outcomes in Transgender and Nonbinary People: An Umbrella Review.","authors":"Kirsten J Hainey,Dean J Connolly,Rachel Thomson,Nova Smalley,Desmond D Campbell,Valerie Wells,Paul Connelly,Christian Delles,Kirstin R Mitchell,S Vittal Katikireddi","doi":"10.1001/jamapsychiatry.2025.1850","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.1850","url":null,"abstract":"ImportanceExperiences of marginalization by gender minority people may predispose them to poorer mental health outcomes than their cisgender peers. Understanding mental health conditions in transgender (trans) and nonbinary people is an essential step in addressing potential inequities in outcome for gender minority people.ObjectiveTo synthesize reviews of mental health and neurodevelopmental conditions in trans and nonbinary people to describe epidemiology, key themes, and research gaps.Evidence ReviewThree bibliographic databases (Embase, MEDLINE, and PsycINFO) were systematically searched from inception to August 21, 2023, to identify reviews addressing mental health and neurodevelopmental outcomes in trans and nonbinary people. Articles were screened by 2 reviewers and prespecified data were extracted. Quality of included reviews was appraised against AMSTAR2 criteria.FindingsOf 7496 unique records, 41 met inclusion criteria with 24 reviews synthesized after excluding those containing overlapping primary studies. Pooled prevalence estimates from meta-analyses were identified for 5 outcomes: suicidal ideation (50%; 95% CI, 42-57), suicide attempts (29%; 95% CI, 25-34), nonsuicidal self-injury (47%; 95% CI, 40-54), eating disorders (18%; 95% CI, 16-19), and autistic spectrum conditions (11%; 95% CI, 8-16). Meta-analyses comparing trans and cisgender groups reported higher odds of suicidal ideation (odds ratio [OR], 3.48; 95% CI, 2.41-4.91), suicide attempts (OR, 3.45; 95% CI, 2.40-4.64), nonsuicidal self-injury (OR, 3.42; 95% CI, 1.99-5.89), and posttraumatic stress disorder (OR, 2.52; 95% CI, 2.22-2.87). Worse outcomes were reported across all narrative syntheses comparing trans and cisgender or general population groups, except for problem gambling, where the limited evidence base was conflicting. No reviews assessed incidence or mortality, and there was limited disaggregation of nonbinary people or by specific gender subgroups (eg, trans men and trans women). Review quality was generally poor. Reviews highlighted heterogeneity in definitions of gender identity and outcome ascertainment, and unrepresentative sample populations as limitations of primary studies.Conclusions and RelevanceA growing body of evidence suggests trans people experience worse mental health outcomes than cisgender people, but there are substantial gaps and methodological weaknesses in existing literature. Research applying an intersectional lens, using longitudinal data and reflecting diversity and the experience of multiple disadvantages in the gender minority population is required to ensure evidence-informed policy and health service development.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"6 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144787103","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":"Racial Differences in Suicide and Undetermined Deaths in Maryland.","authors":"Leslie B Adams,Christopher Kitchen,Paul S Nestadt,Roland J Thorpe,Rhonda C Boyd,Hadi Kharrazi,Holly C Wilcox","doi":"10.1001/jamapsychiatry.2025.1907","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.1907","url":null,"abstract":"ImportanceUndetermined manner of death may obscure the true prevalence of suicide, particularly among Black decedents, and contribute to inequities in health care and autopsy reviews.ObjectiveTo identify and compare health care utilization patterns and classification of death by suicide or undetermined manner of death among Black and White decedents.Design, Setting, and ParticipantsThis retrospective cohort study used data from the Maryland Suicide Data Warehouse (2012-2020), linking Office of the Chief Medical Examiner records with Maryland Health Care Commission claims. The study included Black and White decedents classified by the Office of the Chief Medical Examiner as suicide or undetermined deaths. The analysis focused on Black and White decedents to align with the study's aim of examining disparities between these groups, and they were the only groups with sufficient sample sizes for meaningful comparison. Data were analyzed from January 2024 to March 2024.Main Outcomes and MeasuresPrimary outcomes were manner of death classification and health care use-outpatient, psychiatry, and emergency department visits-in the 12, 6, and 1 month before death. Racial differences by death classification were assessed with χ2 tests.ResultsAmong 15 832 Black and White decedents (4798 Black individuals [30.3%] and 11 034 White individuals [69.7%]; 11 572 [73.1%] male; mean [SD] age, 44 [15.1] years), Black decedents' deaths were disproportionately classified as undetermined rather than suicide (3984 [83.0%]) compared with White decedents (7160 [64.8%]) despite similar patient characteristics. Firearms were the most common method of suicide, while overdose or poisoning predominated among undetermined deaths. White decedents compared with Black decedents were more likely to access outpatient care before death (suicide: 595 [49.5%] compared with 105 [41.5%]; χ2 = 5.0; P = .02; undetermined: 504 [20.8%] compared with 193 [14.9%]; χ2 = 18.9; P < .001). Additionally, more White decedents than Black decedents had psychiatry visits before death: 400 (33.3%) compared with 61 (24.1%) at 12 months (χ2 = 7.7; P = .006), 283 (23.5%) compared with 39 (15.4%) at 6 months (χ2 = 7.5; P = .006), and 187 (15.5%) compared with 23 (9.1%) at 1 month (χ2 = 6.5; P = .01). Emergency department visits were also higher among White decedents compared with Black decedents before death: 94 (7.8%) compared with 10 (4.0%) at 12 months (χ2 = 4.1; P = .04) and 73 (6.1%) compared with 6 (2.4%) at 6 months (χ2 = 4.9; P = .03). However, emergency department visit rates for decedents with undetermined deaths were similar across groups.Conclusions and RelevanceThese findings suggest possible undercounting of suicides and misclassification of undetermined deaths among Black decedents. Addressing these disparities is vital for accurate surveillance and targeted suicide prevention efforts.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"8 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144787102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Energy Homeostasis in Depression Pathophysiology and Its Heterogeneity.","authors":"Giorgio Pistis,Marie-Pierre F Strippoli,Jens H van Dalfsen,Julien Vaucher,Zoltán Kutalik,Peter Vollenweider,Brenda W H J Penninx,Martin Preisig,Yuri Milaneschi","doi":"10.1001/jamapsychiatry.2025.1858","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.1858","url":null,"abstract":"ImportanceEnergy homeostatic dysregulation may constitute 1 module of the heterogeneous pathophysiology of major depressive disorder (MDD), potentially manifesting as a distinctive symptom profile.ObjectiveTo test whether the shared genetic liability of metabolic, interoceptive, and motivational pathways involved in energy homeostasis regulation is associated with the expression of specific MDD symptoms.Design, Setting, and ParticipantsThis study used summary-level data from large genome-wide association studies and individual-level data from 2 prospective psychiatric cohorts, the CoLaus|PsyCoLaus (population-based) and Netherlands Study of Depression and Anxiety (NESDA; clinically enriched) cohorts. Data were retrieved and analyzed from May 2023 through November 2024. A lifetime diagnosis of MDD was ascertained with semistructured diagnostic interviews. The sample comprised 1407 MDD cases and 2020 controls from CoLaus|PsyCoLaus and 1803 MDD cases and 266 controls from NESDA.ExposuresGenomic structural equation modeling was applied to model a unique underlying factor capturing the common genetic liability shared among metabolic and interoceptive signals (body mass index, triglycerides, fasting glucose, C-reactive protein, leptin) and motivational (anhedonia) processes. From this underlying factor, a polygenic score (PGS) was derived, indexing the shared genetic liability of traits potentially involved in energy homeostasis regulation.Main Outcomes and MeasuresA total of 15 depressive symptoms endorsed by participants during MDD.ResultsAmong 1407 MDD cases (66.2% female; median year of birth [YOB], 1956) and 2020 controls (44.3% female; median YOB, 1955) from CoLaus|PsyCoLaus and 1803 MDD cases (68.3% female; median YOB, 1962) and 266 controls (56.0% female; median YOB, 1960) from NESDA, multiple significant bidirectional mendelian randomization estimates and genetic correlations (r = 0.11-0.81) indicated a shared genetic basis between the selected traits, which was modeled as a latent homeostatic factor with genomic structural equation modeling. In cohort data, the PGS indexing the latent homeostatic factor was significantly (false discovery rate, <5%) higher in MDD cases endorsing appetite increase and hypersomnia when contrasted with both controls (appetite increase odds ratio [OR], 2.25 [95% CI, 2.00-2.53]; P = 9.03 × 10-41; hypersomnia OR, 1.22 [95% CI, 1.10-1.35]; P = 1.15 × 10-04) and other MDD cases (appetite increase OR, 1.88 [95% CI, 1.63-2.18]; P = 2.38 × 10-17; hypersomnia OR, 1.18 [95% CI, 1.05-1.33]; P = 5.80 × 10-03).Conclusions and RelevanceThis study identified a module of depression pathophysiology characterized by altered energy homeostasis and associated with the expression of specific symptoms reflecting energy saving and intake responses. These findings could be used to identify patients with depression at higher metabolic risk and could pave the way for the development of targeted treatments.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"52 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144787104","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":"Strengthening Mental Health Systems in Low- and Middle-Income Countries With Routine Outcomes Monitoring.","authors":"Manasi Kumar,Clara Paz,Fredrik Falkeström,Louis Castonguay","doi":"10.1001/jamapsychiatry.2025.1910","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.1910","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"160 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144787433","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":"FDA Eliminates the Clozapine REMS-What Comes Next?","authors":"Deanna L Kelly, John M Kane, Raymond C Love, Robert O Cotes","doi":"10.1001/jamapsychiatry.2025.1155","DOIUrl":"10.1001/jamapsychiatry.2025.1155","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":"751-752"},"PeriodicalIF":17.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215889","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":"Anorexia Nervosa-Facts, Frustrations, and the Future.","authors":"Andrea Phillipou, Ulrike Schmidt, Erica Neill, Stephanie Miles, Patrick McGorry, Kamryn T Eddy","doi":"10.1001/jamapsychiatry.2025.0812","DOIUrl":"10.1001/jamapsychiatry.2025.0812","url":null,"abstract":"<p><strong>Importance: </strong>Anorexia nervosa is a prevalent psychiatric illness associated with exceptionally poor outcomes, including high rates of morbidity and premature mortality. Current evidence-based treatments for anorexia nervosa were developed several decades ago and have limited efficacy. The anorexia nervosa field-and the eating disorders field more broadly-has yet to make significant scientific breakthroughs that lead to acceptable outcomes for people with anorexia nervosa.</p><p><strong>Findings: </strong>This Special Communication highlights how the concurrent psychological and physical symptoms of anorexia nervosa contribute to 2 major problems that have held the anorexia nervosa research field back and hindered research innovations: (1) overspecialization and siloing of the field and (2) an overly narrow focus on weight restoration in treatment.</p><p><strong>Conclusions and relevance: </strong>Specific recommendations are made to help progress the field, including taking a multidisciplinary and collaborative approach to research with colleagues from related disciplines, as well as taking a more holistic approach to understanding and treating anorexia nervosa.</p>","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":"844-847"},"PeriodicalIF":17.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215888","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":"Differential Associations of Dopamine and Serotonin With Reward and Punishment Processes in Humans: A Systematic Review and Meta-Analysis.","authors":"Anahit Mkrtchian, Zeguo Qiu, Yaniv Abir, Tore Erdmann, Quentin Dercon, Terezie Sedlinska, Michael Browning, Harry Costello, Quentin J M Huys","doi":"10.1001/jamapsychiatry.2025.0839","DOIUrl":"10.1001/jamapsychiatry.2025.0839","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Mechanistic biomarkers for guiding treatment selection require selective sensitivity to specific pharmacological interventions. Reinforcement learning processes show potential, but there have been conflicting and sometimes inconsistent reports on how dopamine and serotonin-2 key targets in treating common mental illnesses-affect reinforcement learning in humans.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To perform a meta-analysis of pharmacological manipulations of dopamine and serotonin and examine whether they show distinct associations with reinforcement learning components in humans.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Data sources: &lt;/strong&gt;Ovid MEDLINE/PubMed, Embase, and PsycInfo databases were searched for studies published between January 1, 1946, and January 19, 2023 (repeated April 9, 2024, and October 15, 2024), investigating dopaminergic or serotonergic effects on reward and punishment processes in humans according to PRISMA guidelines.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study selection: &lt;/strong&gt;Studies reporting randomized, placebo-controlled, dopaminergic or serotonergic manipulations on a behavioral outcome from a reward or punishment processing task in healthy humans were included.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Data extraction and synthesis: &lt;/strong&gt;Standardized mean difference (SMD) scores were calculated for the comparison between each drug (dopamine or serotonin) and placebo on a behavioral reward or punishment outcome and quantified in random-effects models for overall reward or punishment processes and 4 main subcategories. Study quality (Cochrane Collaboration tool), moderators, heterogeneity, and publication bias were also assessed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcomes and measures: &lt;/strong&gt;Performance on reward or punishment processing tasks.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In total, 102 studies conducted among healthy volunteers were included (2291 participants receiving dopamine vs 2284 receiving placebo and 1491 receiving serotonin vs 1523 receiving placebo). Dopamine was associated with an increase in overall reward (SMD, 0.18; 95% CI, 0.09 to 0.28) but not punishment function (SMD, -0.06; 95% CI, -0.26 to 0.13). Serotonin was not meaningfully associated with overall punishment (SMD, 0.22; 95% CI, -0.04 to 0.49) or reward (SMD, 0.02; 95% CI, -0.33 to 0.36). Dopaminergic and serotonergic manipulations had distinct associations with subcomponents. Dopamine was associated with reward learning or sensitivity (SMD, 0.26; 95% CI, 0.11 to 0.40), reward discounting (SMD, -0.08; 95% CI, -0.14 to -0.01), and reward vigor (SMD, 0.32; 95% CI, 0.11 to 0.54). By contrast, serotonin was associated with punishment learning or sensitivity (SMD, 0.32; 95% CI, 0.05 to 0.59), reward discounting (SMD, -0.35; 95% CI, -0.67 to -0.02), and aversive pavlovian processes (within-participant studies only; SMD, 0.36; 95% CI, 0.20 to 0.53).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions and relevance: &lt;/strong&gt;In this study, pharmacological manipulations of both dopamine and serotonin had measurable associat","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":"818-829"},"PeriodicalIF":17.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266286","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":"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}