JAMA Psychiatry最新文献

{"title":"Protective Effects of ADHD Medication on Real-World Outcomes.","authors":"Ryan S Sultan,David C Saunders,Jeremy Veenstra-VanderWeele","doi":"10.1001/jamapsychiatry.2025.0918","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.0918","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"9 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144478916","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":"Framework for Brain-Derived Dimensions of Psychopathology.","authors":"Tristram A Lett,Nilakshi Vaidya,Tianye Jia,Elli Polemiti,Tobias Banaschewski,Arun L W Bokde,Herta Flor,Antoine Grigis,Hugh Garavan,Penny Gowland,Andreas Heinz,Rüdiger Brühl,Jean-Luc Martinot,Marie-Laure Paillère Martinot,Eric Artiges,Frauke Nees,Dimitri Papadopoulos Orfanos,Herve Lemaitre,Tomáš Paus,Luise Poustka,Argyris Stringaris,Lea Waller,Zuo Zhang,Jeanne Winterer,Yuning Zhang,Michael N Smolka,Robert Whelan,Ulrike Schmidt,Julia Sinclair,Henrik Walter,Jianfeng Feng,Trevor W Robbins,Sylvane Desrivières,Andre Marquand,Gunter Schumann,","doi":"10.1001/jamapsychiatry.2025.1246","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.1246","url":null,"abstract":"ImportancePsychiatric diagnoses are not defined by neurobiological measures hindering the development of therapies targeting mechanisms underlying mental illness. Research confined to diagnostic boundaries yields heterogeneous biological results, whereas transdiagnostic studies often investigate individual symptoms in isolation.ObjectiveTo develop a framework that groups clinical symptoms compatible with ICD-10 and DSM-5 according to their covariation and shared brain mechanisms.Design, Setting, and ParticipantsThis diagnostic study was conducted in 2 samples, the population-based Reinforcement-Related Behaviour in Normal Brain Function and Psychopathology (IMAGEN) cohort (longitudinal assessments at 14, 19, and 23 years; study duration from March 2010 to the present) and the cross-diagnostic Brain Network Based Stratification of Mental Illness (STRATIFY)/Earlier Detection and Stratification of Eating Disorders and Comorbid Mental Illnesses (ESTRA) samples (study duration from October 2016 to September 2023). The samples are from 8 clinical research hospitals in Germany, the UK, France, and Ireland. For the population-based IMAGEN study, 794 of 1253 23-year-old participants had complete assessments including complete clinical assessments and neuroimaging data across all time points. For the cross-diagnostic STRATIFY/ESTRA samples, 209 of 485 participants aged 18 to 26 years had complete clinical and neuroimaging data. The sample included healthy control individuals and patients with alcohol use disorder, major depressive disorder, anorexia nervosa, and bulimia nervosa.ExposuresSparse generalized canonical correlation analysis was used to integrate diverse data from clinical symptoms and 7 brain imaging modalities.Main Outcomes and MeasuresThe prediction of symptom features was the main outcome. The model was developed in the training set from the IMAGEN Study at age 23 years (70%), then applied in the remaining holdout test sample (30%), the independent STRATIFY/ESTRA patient sample, and longitudinally in the IMAGEN set.ResultsIn total, 1003 participants were included (425 male and 578 female; mean [SD] age, 22.1 [1.5] years). The reassembly of existing ICD-10 and DSM-5 symptoms revealed 6 cross-diagnostic psychopathology scores. They were consistently associated with multimodal neuroimaging components: excitability and impulsivity (training set: r, 0.26; 95% CI, 0.18-0.33; test set: r, 0.22; 95% CI, 0.10-0.35; STRATIFY/ESTRA set: r, 0.19; 95% CI, 0.07-0.31), depressive mood and distress (training: r, 0.30; 95% CI, 0.20-0.38; test: r, 0.22; 95% CI, 0.09-0.35; STRATIFY/ESTRA: r, 0.19; 95% CI, 0.04-0.33), emotional and behavioral dysregulation (training: r, 0.40; 95% CI, 0.31-0.48; test: r, 0.17; 95% CI, 0.14-0.36; STRATIFY/ESTRA: r, 0.19; 95% CI, 0.06-0.30), stress pathology (training: r, 0.32; 95% CI, 0.19-0.43; test: r, 0.14; 95% CI, 0.05-0.23; STRATIFY/ESTRA: r, 0.12; 95% CI, 0.01-0.22), eating pathology (training: r, 0.34; 95% CI, 0.25-0.42; t","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"13 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319997","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":"Sweetened Beverages and Incident All-Cause Dementia Among Older Adults","authors":"Hui Chen, Yihong Ding, Klodian Dhana, Puja Agarwal, Todd Beck, Kumar B. Rajan, Debora Melo van Lent, Yuan Ma, Geng Zong, Kjetil Bjornevik, Changzheng Yuan","doi":"10.1001/jamapsychiatry.2025.1230","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.1230","url":null,"abstract":"ImportanceIntake of sweetened beverages, including sugar-sweetened beverages (SSB) and artificially sweetened beverages (ASB), has been linked to multiple health outcomes, but their associations with dementia risk among older adults are unclear.ObjectiveTo assess whether the consumption of SSB and ASB is associated with the risk of all-cause dementia in older adults.Design, Setting, and ParticipantsThis multicohort study examined data from US adults aged 65 and older enrolled in the Health and Retirement Study (2013), the Atherosclerosis Risk in Communities study (1987-1995), the Chicago Healthy and Aging Project (1993-2012), the Rush Memory and Aging Project (1997-2005), the Framingham Heart Study original cohort (1986-1994), and its offspring cohort (1991-2001). Data were analyzed from May 27 to September 24, 2024.ExposuresSSB and ASB intake was assessed using validated food frequency questionnaires.Main Outcomes and MeasuresThe primary outcome was all-cause dementia ascertained at least 2 years after baseline from active research follow-ups and passive surveillance. Cox proportional hazard regression models were used to assess the associations of SSB and ASB with incident dementia.ResultsOf 10 974 participants (60.0% female, mean [SD] age: 73.2 [6.8] years), 2445 developed incident all-cause dementia over 116 067 person-years of follow-up. Consumption of SSB and ASB in older adulthood was not associated with dementia risk in later life. The pooled hazard ratio (HR) per serving per week for SSB was 0.99 (95% CI, 0.98-1.01; <jats:italic>P</jats:italic> = .18; <jats:italic>I</jats:italic><jats:sup>2</jats:sup> = 0%) and for ASB was 1.00 (95% CI, 0.99-1.01; <jats:italic>P</jats:italic> = .99; <jats:italic>I</jats:italic><jats:sup>2</jats:sup> = 1%). The pooled HRs comparing the highest (≥1 serving per day) with lowest (0 to &amp;amp;lt;1 serving per month) consumption groups were 0.90 (95% CI, 0.78-1.03) for SSB and 1.00 (95% CI, 0.83-1.21) for ASB. These findings were similar across cohorts and subgroups. In contrast, an inverse association was observed for the Mediterranean diet score (HR, 0.92; 95% CI, 0.85-0.99 per 5-unit increment) as a positive control.Conclusions and RelevanceIn this study, late-life consumption of SSB or ASB was not associated with the risk of dementia. However, given their detrimental effects on metabolic health and related chronic diseases during early life and midlife, the effects of early-life consumption of SSB and ASB on the risk of dementia warrant further investigation.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"15 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319999","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":""},"PeriodicalIF":17.1,"publicationDate":"2025-06-11","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":"Rescheduling Cannabis-Medicine or Politics?","authors":"Bertha K Madras, Paul J Larkin","doi":"10.1001/jamapsychiatry.2025.1116","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.1116","url":null,"abstract":"<p><strong>Importance: </strong>In 2023, the US Department of Health and Human Services (HHS) issued a letter to the administrator of the Drug Enforcement Administration (DEA) recommending rescheduling of cannabis (marijuana) from Schedule I to Schedule III under the Controlled Substances Act (CSA). This recommendation marked a significant departure from previous, consistent, and long-standing federal decisions on cannabis scheduling.</p><p><strong>Objective: </strong>To critique the arguments made by HHS for recommending marijuana rescheduling.</p><p><strong>Evidence: </strong>The HHS secretary (advisor) and US attorney general (decision maker) must consider 8 factors and a 5-part test when deciding whether to reschedule a controlled substance. CSA classification criteria include whether a drug has currently accepted medical use, whether it has abuse potential, and whether use is safe under medical supervision. HHS undermined these established legal scheduling criteria by introducing new, untested criteria.</p><p><strong>Findings: </strong>HHS failed to adequately address the adverse effects of cannabis use, including the high prevalence of cannabis use disorder among users, risks associated with youth consumption, growing evidence linking cannabis to psychosis, and other significant concerns. HHS asserted that cannabis is widely accepted as a legitimate form of medicine, despite the reality that only a small fraction of patient-care physicians recommend it for symptom relief, in practices that often diverge from the norms of medical practice. Finally, the US Food and Drug Administration has not approved cannabis as a medicine, as evidence is deficient in several key areas, including data from high-quality clinical trials, standardized cannabis formulations, established purity, defined routes of administration, dosing guidelines, and specific frequencies of use.</p><p><strong>Conclusions and relevance: </strong>The HHS rationale for reclassifying cannabis in myriad forms (edibles, smokables, drinkables, vaping products, suppositories) and potencies relies on a questionable selection of comparator drugs, downplays distinctive adverse events among cannabis users, and claims, unconvincingly, that cannabis has wide acceptance in medical practice supported by scientific evidence.</p>","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":""},"PeriodicalIF":22.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266287","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":"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":""},"PeriodicalIF":22.5,"publicationDate":"2025-06-11","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":"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":"https://doi.org/10.1001/jamapsychiatry.2025.1155","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":""},"PeriodicalIF":22.5,"publicationDate":"2025-06-04","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":"https://doi.org/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":""},"PeriodicalIF":22.5,"publicationDate":"2025-06-04","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":"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":""},"PeriodicalIF":22.5,"publicationDate":"2025-06-04","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":"&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To examine whether simvastatin added to escitalopram is efficacious in improving depressive symptoms compared with add-on placebo.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design, setting, and participants: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Interventions: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcomes and measures: &lt;/strong&gt;The primary outcome was change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline (week 0) to week 12.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;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 &lt; .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 &lt; .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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions and relevance: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Trial registration: &lt;/","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":""},"PeriodicalIF":22.5,"publicationDate":"2025-06-04","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}