JAMA Psychiatry最新文献

{"title":"Ethical Dilemmas of Antipsychotic Discontinuation","authors":"Helene Speyer, John Lysaker, David Roe","doi":"10.1001/jamapsychiatry.2025.1702","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.1702","url":null,"abstract":"This Viewpoint discusses the process of shared decision-making between clinicians and patients when considering the discontinuation of antipsychotic medication and proposes a shift toward an alternative process of shared deliberation.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"30 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640358","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":"Medicaid 1115 Waivers for Mental Health-Time for Redesign?","authors":"K John McConnell,Jennifer D Hall,Benjamin F Miller","doi":"10.1001/jamapsychiatry.2025.1607","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.1607","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"146 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586623","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":"Incidence and Nature of Antidepressant Discontinuation Symptoms: A Systematic Review and Meta-Analysis.","authors":"Michail Kalfas,Dimosthenis Tsapekos,Matthew Butler,Robert A McCutcheon,Toby Pillinger,Rebecca Strawbridge,Bhagyashree Bhaskar Bhat,Peter M Haddad,Philip J Cowen,Oliver D Howes,Dan W Joyce,David J Nutt,David S Baldwin,Carmine M Pariante,Gemma Lewis,Allan H Young,Glyn Lewis,Joseph F Hayes,Sameer Jauhar","doi":"10.1001/jamapsychiatry.2025.1362","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.1362","url":null,"abstract":"ImportanceThe incidence and nature of discontinuation symptoms following antidepressant cessation remain unclear.ObjectiveTo examine the presence of discontinuation symptoms using standardized scales (eg, Discontinuation-Emergent Signs and Symptoms [DESS]) and the incidence of individual discontinuation symptoms in individuals who stop taking antidepressants.Data SourcesThe databases Embase, PsycINFO, Ovid MEDLINE, and Cochrane Library were systematically searched from inception until November 7, 2023.Study SelectionRandomized clinical trials (RCTs) reporting discontinuation symptoms using a standardized scale or individual symptoms (eg, adverse events) following antidepressant cessation were included.Data Extraction and SynthesisData extracted were cross-checked by 2 reviewers. Additional unpublished data from 11 RCTs were included. A random-effects meta-analysis was conducted to calculate standardized mean difference between individuals who discontinued an antidepressant vs those who continued an antidepressant or discontinued placebo. A proportion and odds ratio (OR) meta-analysis was performed to assess incidence of individual discontinuation symptoms compared to placebo. Subgroup analyses were conducted to compare different antidepressants. Data analysis was conducted between September 2024 and December 2024.Main Outcomes and MeasuresThe primary outcomes were incidence and nature of antidepressant discontinuation symptoms measured using standardized or unstandardized scales.ResultsA total of 50 studies were included, 49 of which were included in meta-analyses. The 50 studies included 17 828 participants in total, with 66.9% female participants and mean participant age of 44 years. Follow-up was between 1 day and 52 weeks. The DESS meta-analysis indicated increased discontinuation symptoms at 1 week in participants stopping antidepressants (standardized mean difference, 0.31; 95% CI, 0.23-0.39; number of studies [k] = 11; n = 3915 participants) compared to those taking placebo or continuing antidepressants. The effect size was equivalent to 1 more symptom on the DESS. Discontinuation of antidepressants was associated with increased odds of dizziness (OR, 5.52; 95% CI, 3.81-8.01), nausea (OR, 3.16; 95% CI, 2.01-4.96), vertigo (OR, 6.40; 95% CI, 1.20-34.19), and nervousness (OR, 3.15; 95% CI, 1.29-7.64) compared to placebo discontinuation. Dizziness was the most prevalent discontinuation symptom (risk difference, 6.24%). Discontinuation was not associated with depression symptoms, despite being measured in people with major depressive disorder (k = 5).Conclusions and RelevanceThis systematic review and meta-analysis indicated that the mean number of discontinuation symptoms at week 1 after stopping antidepressants was below the threshold for clinically significant discontinuation syndrome. Mood worsening was not associated with discontinuation; therefore, later presentation of depression after discontinuation is indicative of depression relapse","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"21 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586699","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":"Current Position and Future Direction of Inflammation in Neuropsychiatric Disorders: A Review.","authors":"Rachel Upthegrove,Fabiana Corsi-Zuelli,Amalie C M Couch,Nicholas M Barnes,Anthony C Vernon","doi":"10.1001/jamapsychiatry.2025.1369","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.1369","url":null,"abstract":"ImportanceThere has been a large increase in research focusing on inflammation across psychiatric disorders, with the hope of achieving breakthroughs seen with this approach in cancer and other conditions. Current findings suggest that immune-related pathophysiological processes involving inflammation could play a key role for many major mental illnesses. How far reaching this role would be and how soon we can expect translation into treatment, however, remain open questions.ObservationsIn this narrative review, new evidence from clinical populations, new trials, and preclinical models was summarized. Converging evidence suggests that inflammation plays a significant role in subgroups of patients with psychosis, depression, and autism. Interleukin (IL) 6, T-cell control, immune-metabolic function, and the complement system represent fundamental areas of further research. New treatments have yet to reach clinical impact, but targeted trials are ongoing. Developing and refining human cellular models will aid mechanistic target validation and further understanding of causal pathways and networks.Conclusions and RelevanceTo advance to and achieve clinical impact, investigations need to include a collaborative, united effort, pulling information across disciplines and translational scales. A focused approach is needed to validate key emerging targets, where evidence and potential for new and repurposed treatments are strongest.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"28 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586472","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":"Profiles of Genetic Risks for Psychotic Disorders.","authors":"Kenneth S Kendler,Henrik Ohlsson,Jan Sundquist,Kristina Sundquist","doi":"10.1001/jamapsychiatry.2025.1289","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.1289","url":null,"abstract":"ImportanceThe etiologic interrelationship of 4 rare/controversial psychotic disorders (delusional disorder [DD], acute psychoses [AP], psychosis not otherwise specified [PNOS], and schizoaffective disorder [SAD]) is poorly understood.ObjectiveTo assess levels of the family genetic risk score (FGRS) for schizophrenia (SZ), bipolar disorder (BD), and major depression (MD) in individuals with DD, AP, PNOS, and SAD, thereby clarifying their genetic relationships.Design, Setting, and ParticipantsThis cohort study included all individuals born in Sweden between 1950 and 2000 to Swedish-born parents followed up until 2018 with diagnoses of MD, BD, SZ, SAD, AP, PNOS, and DD, based on diagnosis codes from national registries.ExposuresFGRS for SZ, BD, and MD calculated from first- through fifth-degree relatives, controlling for cohabitation.Main Outcomes and MeasuresDiagnoses of DD, AP, PNOS, and SAD.ResultsIn the cohort, 667 012 individuals had MD (420 142 females [63%] and 246 870 males [37.0%]), 58 385 had BD (36 344 females [62%] and 22 041 males [38%]), 17 465 had SZ (6330 females [36%] and 11 135 males [64%]), 7597 had SAD (4125 females [54%] and 3472 males [46%]), 16 315 had AP (7907 females [49%] and 8408 males [51%]), 27 127 had PNOS (12 277 females [45%] and 14 850 males [55%]), and 11 560 had DD (5060 females [44%] and 6500 males [56%]). On \"genetic maps\" of SZ FGRS, BD FGRS, and MD FGRS, DD stood alone with approximately half the genetic risk for SZ compared with SZ cases and similar levels of BD and MD risk. SAD was also distinct as the only disorder with quite high genetic risks for both SZ and BD and was clearly separable from psychotic BD. AP and PNOS had similar genetic profiles with levels of SZ FGRS similar to DD but higher levels of genetic risk for BD and MD. Subdividing psychoses by outcome produced minimal effects on the DD genetic profile, moderate effects on AP and PNOS, and large effects on SAD, with good social outcomes associated with decreased SZ FGRS and increased BD FGRS.Conclusions and RelevanceIn a Swedish population, none of the 4 disorders appeared, from a genetic perspective, to be subtypes of SZ, BD, or MD. Further genetics research on the syndromes of DD, AP, PNOS, and SAD have much to teach about the relationship between dimensions of genetic risks and the clinical presentation and course of psychotic illness.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"26 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586696","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 Antecedents and Correlates of 2 Distinct Developmental Pathways to Suicidal Ideation.","authors":"Marie-Claude Geoffroy,Sasha MacNeil,Vincent Paquin,Ayla Inja,Alain Girard,Élise Chartrand,Natalie Castellanos-Ryan,Charles-Édouard Notredame,Ian Colman,Massimiliano Orri,Gustavo Turecki,Sylvana Côté","doi":"10.1001/jamapsychiatry.2025.1273","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.1273","url":null,"abstract":"ImportanceSuicidal ideation is increasingly common in youth. Trajectories and associated mental health symptoms across development remain poorly understood.ObjectiveTo describe trajectories of suicidal ideation from early adolescence to young adulthood and identify preceding and co-occurring mental health symptoms to inform optimal prevention.Design, Setting, and ParticipantsThis cohort study used data from a contemporary, longitudinal cohort study, the Québec Longitudinal Study of Child Development (QLSCD), including reports from participants, parents, and teachers. The QLSCD is a population-based birth cohort study of 2120 singletons born between 1997 and 1998 in Québec, Canada, and followed up to age 25 years (2023). Data were analyzed from September 2024 to February 2025.Main Outcomes and MeasuresSerious suicidal ideation in the past 12 months was assessed by a question to participants at ages 13, 15, 17, 20, 23, and 25 years.ExposuresMental health symptoms (eg, internalizing, externalizing) as reported by parents, teachers, and self-reports on validated questionnaires and standardized across 5 developmental periods: preschool (3-5 years), childhood (6-12 years), early adolescence (13 years), mid-late adolescence (15-17 years), and young adulthood (20-25 years).ResultsA total of 1635 participants (845 female [51.7%]; participant number is weighted to account for selective attrition) provided answers on suicidal ideation, with survey weights applied. A total of 3 trajectories were identified: minimal/no ideation (1433 [87.6%]), onset in early adolescence (117 [7.1%]), and onset in young adulthood (86 [5.2%]). Relative to minimal/no ideation, onset in early adolescence was associated with elevated symptoms across nearly all mental health indicators from childhood through adulthood. This included both internalizing (eg, childhood depressive symptoms: risk ratio [RR], 1.75; 95% CI, 1.45-2.05) and externalizing (eg, childhood disruptive symptoms: RR, 1.60; 95% CI, 1.29-1.91) symptoms and maternal antisocial symptoms (RR, 1.39; 95% CI, 1.11-1.66). In contrast, onset of suicidal ideation in young adulthood was associated with internalizing symptoms (eg, mid-late adolescence depressive symptoms: RR, 1.84; 95% CI, 1.28-2.39) emerging in adolescence and worsening mental distress in young adulthood.Conclusions and RelevanceResults of this cohort study revealed 2 pathways to suicidal ideation: onset in early adolescence, with persistent childhood internalizing/externalizing symptoms, and onset in young adulthood linked to internalizing symptoms emerging in adolescence without prior distress. Findings suggest timely addressing of mental health symptoms and developmental stage-specific prevention.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"3 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533376","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":"Data-Driven Contingency Management Incentive Magnitudes: A Review.","authors":"Carla J Rash,Sonata I Black,Sara C Parent,Tyler G Erath,Michael G McDonell","doi":"10.1001/jamapsychiatry.2025.1341","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.1341","url":null,"abstract":"ImportanceInterest in contingency management (CM) as a treatment for opioid and stimulant use disorders has increased because of the ongoing dual opioid/stimulant crisis, rising stimulant drug deaths, and demand for effective treatments for stimulant use disorder. The success of the US Department of Veterans Affairs nationwide rollout and the launch of California's Recovery Incentives Program provide evidence that this treatment can be translated into effective clinical practice.ObjectiveTo provide data-driven inflation-adjusted incentive estimates for modern CM protocols that can be customized for intervention duration. It is essential for CM protocols implemented in clinical care to use efficacious, research-supported parameters, including incentive magnitude.Evidence ReviewThis review included 112 published CM protocols that involved reinforcement of stimulant- and/or opioid-negative urine drug tests, categorized each protocol in terms of impact (small/medium/large effect size) relative to a non-CM comparator condition, and computed weekly inflation-adjusted incentive magnitudes for voucher- and prize-based CM protocols.FindingsDrawn from protocols with medium to large impacts on patient outcomes, weekly median magnitude estimates are $128/week for voucher protocols and $55/week for prize protocols. For the most common duration of 12 weeks, these estimates translate to $1536 for voucher and $660 for prize protocols.Conclusions and RelevanceThese incentive magnitude estimates can be used to inform clinical, policy, and advocacy related to CM implementation. Practical suggestions (eg, starting values, escalation) for building protocols that meet these incentive magnitudes are provided and implications are discussed.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"13 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533568","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":"Esketamine Monotherapy in Adults With Treatment-Resistant Depression: A Randomized Clinical Trial.","authors":"Adam Janik,Xin Qiu,Rosanne Lane,Vanina Popova,Wayne C Drevets,Carla M Canuso,Matthew Macaluso,Gregory W Mattingly,Richard C Shelton,John M Zajecka,Dong-Jing Fu","doi":"10.1001/jamapsychiatry.2025.1317","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.1317","url":null,"abstract":"ImportanceEsketamine nasal spray, administered in conjunction with an oral antidepressant, is approved for treatment-resistant depression (TRD). However, the efficacy of esketamine nasal spray administered as monotherapy for patients with TRD has not yet been evaluated.ObjectiveTo assess the efficacy and safety of esketamine monotherapy compared to placebo in reducing depressive symptoms in patients with TRD.Design, Setting, and ParticipantsThis phase 4, double-blind, placebo-controlled randomized clinical trial was conducted from November 2020 to January 2024 at 51 outpatient centers in the US. Adults with major depressive disorder (DSM-5 criteria) without psychotic features who experienced inadequate response (≤25% improvement) to 2 or more oral antidepressants during the current depressive episode were eligible for inclusion. Data analyses were conducted from March 1, 2024, to July 8, 2024.InterventionsAfter a 2-week or longer antidepressant-free period, participants were randomized at a 1:1:2 ratio to fixed-dose intranasal esketamine (56 mg or 84 mg) or matching intranasal placebo, administered twice weekly for 4 weeks.Main Outcomes and MeasuresChange in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to day 28 (primary efficacy end point) and to 24 hours post-first dose (day 2; key secondary efficacy end point) were analyzed by a mixed-effects model using repeated measures.ResultsIn this multicenter randomized clinical trial, 378 participants who met prerandomization MADRS severity criteria received 1 or more study drug doses (esketamine, 56 mg [n = 86]; esketamine, 84 mg [n = 95]; or placebo [n = 197]). Mean (SD) participant age was 45.4 (14.1) years, 231 participants (61.1%) were female, and baseline mean (range) MADRS total score was 37.3 (28-50). At day 28, the least-square (LS) mean difference (SE) between esketamine and placebo was -5.1 (1.42) (95% CI, -7.91 to -2.33) for the 56-mg dose and -6.8 (1.38) (95% CI, -9.48 to -4.07) for the 84-mg dose (for each, 2-sided P < .001). Observed effect sizes were 0.48 and 0.63 for the 56-mg and 84-mg dose groups, respectively. At day 2 (approximately 24 hours post-first dose), the between-group difference was significant for both esketamine doses: -3.8 (1.29) (95% CI, -6.29 to -1.22; 2-sided P = .004) for 56 mg and -3.4 (1.24) (95% CI, -5.89 to -1.00; 2-sided P = .006) for 84 mg. The most common treatment-emergent adverse events reported for esketamine (combined doses) were nausea (56 participants [24.8%]), dissociation (55 [24.3%]), dizziness (49 [21.7%]), and headache (43 [19.0%]).Conclusions and RelevanceAccording to results of this multicenter, double-blind randomized clinical trial, esketamine monotherapy may expand treatment options for adult patients with TRD by addressing an unmet need of patients experiencing treatment-limiting tolerability concerns and nonresponse with oral antidepressants.Trial RegistrationClinicalTrials.gov Identifier: NCT04599855.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"19 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533573","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":"Purposeful Drug Repurposing.","authors":"Peter Nagele, Charles R Conway, Charles F Zorumski","doi":"10.1001/jamapsychiatry.2025.0900","DOIUrl":"10.1001/jamapsychiatry.2025.0900","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":"638-639"},"PeriodicalIF":22.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969968","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":"Childhood Maternal Warmth, Social Safety Schemas, and Adolescent Mental and Physical Health.","authors":"Jenna Alley, Dimitris I Tsomokos, Summer Mengelkoch, George M Slavich","doi":"10.1001/jamapsychiatry.2025.0815","DOIUrl":"10.1001/jamapsychiatry.2025.0815","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Although early maternal warmth strongly predicts adolescent health, questions remain about the biopsychosocial mechanisms underlying this association.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To understand how maternal warmth at 3 years of age shapes adolescent social safety schemas at 14 years of age and physical and mental health at 17 years of age.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design, setting, and participants: &lt;/strong&gt;The Millennium Cohort Study tracks approximately 19 200 children born from late 2000 to early 2002 in the UK. Participants were assessed from ages 3 to 17 years.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Exposure: &lt;/strong&gt;Low maternal warmth (eg, lack of praise, negative tone of voice when speaking to the child) and maternal harshness (eg, using physical restraint, grabbing the child) were independently coded during a home visit (age 3 years).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcomes and measures: &lt;/strong&gt;Social safety (age 14 years) was measured by children's responses to 3 items (eg, \"I have family and friends who help me feel safe, secure and happy\"). Physical health was self-reported on a scale ranging from 1 (excellent) to 5 (poor) (age 17 years). Psychological distress (age 17 years) was assessed using the 6-item Kessler Psychological Distress Scale. Psychiatric problems (age 17 years) was a latent variable composed of self-disclosed clinical diagnosis of depression/anxiety, self-harm, and suicidal behaviors.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The present sample included 8540 youths (52% female; 3.0% Black or Black British, 2.8% Indian, 6.7% Pakistani and Bangladeshi, 2.8% Mixed, 83% White, and 1.6% other). Data were analyzed from March 2024 to September 2024 using structural equation modeling. In models controlling for sex, ethnicity, income, neighborhood disadvantage, maternal mental health, and early cognitive ability, the paths from childhood maternal warmth (but not harshness) to social safety schemas at 14 years of age (b = 0.03; P &lt; .001) and physical health at 17 years of age (b = 0.05; P = .02) were significant, suggesting that early maternal warmth enhances subsequent perceived social safety and physical health. Additionally, the paths from negative social safety schemas at 14 years of age to poorer physical health (b = 0.50; P &lt; .001), psychological distress (b = 5.37; P &lt; .001), and psychiatric problems (b = 0.21; P &lt; .001) at 17 years of age were significant, suggesting that greater perceived social safety prospectively predicts better health. Social safety at 14 years of age mediated 20% to 100% of the effect of early maternal warmth on physical health, psychological distress, and psychiatric problems at 17 years of age (b = 0.01-0.15; P &lt; .001 for all).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions and relevance: &lt;/strong&gt;These results show that early-life maternal warmth affected adolescent health by influencing perceptions of social safety. Improving parent-child relationships and enhancing youths' perceptions of social safety may thus improve adolescent h","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":"709-717"},"PeriodicalIF":22.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12120678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159155","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}