Pub Date : 2026-01-14DOI: 10.1001/jamapsychiatry.2025.4253
Arnav Gupta,Tushar Tejpal,Chanhee Seo,Nicholas Fabiano,Selina Zhao,Stanley Wong,Yuan Qiu,Jenna MacNeil,Dain R Kim,Natasha Aleksova,Sara Siddiqi,Marco Solmi,Jess G Fiedorowicz
ImportanceMental disorders have been associated with traditional cardiovascular risk factors that may mediate the risk of acute coronary syndrome (ACS).ObjectiveTo estimate the association of ACS among patients with mental disorders, as compared with patients without mental disorders.Data SourcesMEDLINE, Embase, and PubMed were searched for studies between July 1, 2025, and date of database inception.Study SelectionStudy screening was performed in duplicates with conflicts resolved upon consensus. Inclusion criteria were as follows: (1) observational or randomized study, (2) measured association with ACS (incident events, risk ratio, odds ratio, hazard ratio [HR]), and (3) investigated any clinical mental disorder (based on DSM and International Classification of Diseases) before ACS events.Data Extraction and SynthesisThis systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Data extraction was performed in duplicate and resolved on consensus. Data were quantitatively synthesized through random-effects meta-analysis. The National Institutes of Health Study Quality Assessment Tools were used to assess the quality of included studies. Studies were analyzed from January 1966 to October 2021.Main Outcomes and MeasuresAssociation and/or risk of ACS.ResultsAmong 3616 initially identified studies, 25 full-text articles met inclusion criteria with 22 048 504 participants of median (IQR) age 48.0 (34.5-56.1) years, with 13 019 897 males (59.1%). Depressive disorder (HR, 1.40; 95% CI, 1.11-1.78; P = .01; Grading of Recommendations Assessment, Development, and Evaluation [GRADE] certainty = very low), anxiety disorder (HR, 1.63; 95% CI, 1.40-1.89; P < .001; GRADE certainty = low), sleep disorder (HR, 1.60; 95% CI, 1.22-2.10; P < .001; GRADE certainty = low), and posttraumatic stress disorder (PTSD; HR, 2.73; 95% CI, 1.94-3.84; P < .001; GRADE certainty = moderate) were associated with increased risk of ACS. Bipolar (HR, 1.48; 95% CI, 0.47-4.61; P = .28; GRADE certainty = very low) and psychotic (HR, 0.97; 95% CI, 0.01-178.30; P = .06; GRADE certainty = very low) disorders were not significantly associated with increased risk of acute myocardial infarction, although they had similar point estimates to some other mental disorders.Conclusions and RelevanceResults of this systematic review and meta-analysis suggest that depressive disorders, anxiety disorders, PTSD, and sleep disorders were associated with an increased risk of ACS. Particularly, PTSD and sleep disorders emerged as significant risk factors for ACS, indicating the potential impact of sleep quality on cardiovascular outcomes. Future research addressing these limitations could provide more nuanced insights into the association between mental health and ACS.
重要的是，精神疾病与传统的心血管危险因素有关，这些因素可能介导急性冠脉综合征（ACS）的风险。目的评估精神障碍患者与无精神障碍患者ACS的相关性。数据来源medline， Embase和PubMed检索了2025年7月1日至数据库建立日期之间的研究。研究选择研究筛选按重复进行，冲突在一致意见下解决。纳入标准如下：(1)观察性或随机研究，(2)测量与ACS的相关性（事件事件、风险比、优势比、危险比[HR]），(3)调查ACS事件发生前的任何临床精神障碍（基于DSM和国际疾病分类）。本系统评价遵循系统评价和荟萃分析首选报告项目（PRISMA） 2020指南。数据提取一式两份，协商一致解决。通过随机效应荟萃分析定量合成数据。使用美国国立卫生研究院研究质量评估工具评估纳入研究的质量。研究分析了从1966年1月到2021年10月的研究。主要结局和测量ACS的关联和/或风险。结果在最初确定的3616项研究中，25篇全文文章符合纳入标准，22 048 504名参与者中位（IQR）年龄为48.0（34.5-56.1）岁，其中13 019 897名男性（59.1%）。抑郁症（HR, 1.40; 95% CI, 1.11-1.78; P = 0.01；建议分级评估、发展和评价[GRADE]确定性=极低）、焦虑症（HR, 1.63; 95% CI, 1.40-1.89; P < 0.001； GRADE确定性=低）、睡眠障碍（HR, 1.60; 95% CI, 1.22-2.10; P < 0.001； GRADE确定性=低）和创伤后应激障碍（PTSD； HR, 2.73; 95% CI, 1.94-3.84; P < 0.001； GRADE确定性=中等）与ACS风险增加相关。双相障碍（HR, 1.48; 95% CI, 0.47-4.61; P = 0.28； GRADE确定性=极低）和精神障碍（HR, 0.97; 95% CI, 0.01-178.30; P = 0.06； GRADE确定性=极低）与急性心肌梗死风险增加没有显著相关，尽管它们与其他一些精神障碍有相似的点估计。结论和相关性本系统综述和荟萃分析的结果表明，抑郁症、焦虑症、创伤后应激障碍和睡眠障碍与ACS风险增加相关。特别是，PTSD和睡眠障碍成为ACS的重要危险因素，表明睡眠质量对心血管结局的潜在影响。针对这些局限性的未来研究可以为心理健康和ACS之间的关系提供更细致的见解。
{"title":"Mental Disorders as a Risk Factor of Acute Coronary Syndrome: A Systematic Review and Meta-Analysis.","authors":"Arnav Gupta,Tushar Tejpal,Chanhee Seo,Nicholas Fabiano,Selina Zhao,Stanley Wong,Yuan Qiu,Jenna MacNeil,Dain R Kim,Natasha Aleksova,Sara Siddiqi,Marco Solmi,Jess G Fiedorowicz","doi":"10.1001/jamapsychiatry.2025.4253","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.4253","url":null,"abstract":"ImportanceMental disorders have been associated with traditional cardiovascular risk factors that may mediate the risk of acute coronary syndrome (ACS).ObjectiveTo estimate the association of ACS among patients with mental disorders, as compared with patients without mental disorders.Data SourcesMEDLINE, Embase, and PubMed were searched for studies between July 1, 2025, and date of database inception.Study SelectionStudy screening was performed in duplicates with conflicts resolved upon consensus. Inclusion criteria were as follows: (1) observational or randomized study, (2) measured association with ACS (incident events, risk ratio, odds ratio, hazard ratio [HR]), and (3) investigated any clinical mental disorder (based on DSM and International Classification of Diseases) before ACS events.Data Extraction and SynthesisThis systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Data extraction was performed in duplicate and resolved on consensus. Data were quantitatively synthesized through random-effects meta-analysis. The National Institutes of Health Study Quality Assessment Tools were used to assess the quality of included studies. Studies were analyzed from January 1966 to October 2021.Main Outcomes and MeasuresAssociation and/or risk of ACS.ResultsAmong 3616 initially identified studies, 25 full-text articles met inclusion criteria with 22 048 504 participants of median (IQR) age 48.0 (34.5-56.1) years, with 13 019 897 males (59.1%). Depressive disorder (HR, 1.40; 95% CI, 1.11-1.78; P = .01; Grading of Recommendations Assessment, Development, and Evaluation [GRADE] certainty = very low), anxiety disorder (HR, 1.63; 95% CI, 1.40-1.89; P < .001; GRADE certainty = low), sleep disorder (HR, 1.60; 95% CI, 1.22-2.10; P < .001; GRADE certainty = low), and posttraumatic stress disorder (PTSD; HR, 2.73; 95% CI, 1.94-3.84; P < .001; GRADE certainty = moderate) were associated with increased risk of ACS. Bipolar (HR, 1.48; 95% CI, 0.47-4.61; P = .28; GRADE certainty = very low) and psychotic (HR, 0.97; 95% CI, 0.01-178.30; P = .06; GRADE certainty = very low) disorders were not significantly associated with increased risk of acute myocardial infarction, although they had similar point estimates to some other mental disorders.Conclusions and RelevanceResults of this systematic review and meta-analysis suggest that depressive disorders, anxiety disorders, PTSD, and sleep disorders were associated with an increased risk of ACS. Particularly, PTSD and sleep disorders emerged as significant risk factors for ACS, indicating the potential impact of sleep quality on cardiovascular outcomes. Future research addressing these limitations could provide more nuanced insights into the association between mental health and ACS.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"120 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145961299","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}
Pub Date : 2026-01-14DOI: 10.1001/jamapsychiatry.2025.4116
Roy H Perlis
ImportanceThe potential of tools using artificial intelligence (AI) to address the many challenges in delivery of mental health care has been widely discussed. However, the possible negative consequences of AI for such care have received less attention.ObservationsIntegrating AI with mental health care has the potential to expand access and improve quality of care. It may also contribute to improvements in diagnosis, risk stratification, and development of novel therapeutics. At the same time, availability of AI chatbots and stratification algorithms may diminish access to human-delivered care. Reliance on AI tools may have other unanticipated adverse consequences on clinical practice, including diminished human clinician skill. The probabilistic nature of many of these tools, including large language models, makes their capacity to cause harm difficult to determine.Conclusions and RelevanceThe likely benefits of AI for psychiatric care delivery must be balanced against substantial risks. Strategies to mitigate this risk may require regulation to enhance transparency and systematically evaluate the impact of AI in practice, as well as clinician training to make optimal use of these emerging methods.
{"title":"Artificial Intelligence and the Potential Transformation of Mental Health.","authors":"Roy H Perlis","doi":"10.1001/jamapsychiatry.2025.4116","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.4116","url":null,"abstract":"ImportanceThe potential of tools using artificial intelligence (AI) to address the many challenges in delivery of mental health care has been widely discussed. However, the possible negative consequences of AI for such care have received less attention.ObservationsIntegrating AI with mental health care has the potential to expand access and improve quality of care. It may also contribute to improvements in diagnosis, risk stratification, and development of novel therapeutics. At the same time, availability of AI chatbots and stratification algorithms may diminish access to human-delivered care. Reliance on AI tools may have other unanticipated adverse consequences on clinical practice, including diminished human clinician skill. The probabilistic nature of many of these tools, including large language models, makes their capacity to cause harm difficult to determine.Conclusions and RelevanceThe likely benefits of AI for psychiatric care delivery must be balanced against substantial risks. Strategies to mitigate this risk may require regulation to enhance transparency and systematically evaluate the impact of AI in practice, as well as clinician training to make optimal use of these emerging methods.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"216 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145961300","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}
Pub Date : 2026-01-14DOI: 10.1001/jamapsychiatry.2025.4106
Katrine Komischke,Paul A Boelen,Fiona Maccallum,Maja O'Connor
ImportanceGrief-focused cognitive behavioral therapies (GF-CBTs) are found effective in treating prolonged grief disorder (PGD), but the relative efficacy of different delivery formats is unknown. While evidence for individual GF-CBT (GF-CBT individual) is well established, evidence for group GF-CBT (GF-CBT group) is scarce. However, the group format holds possible advantages in a bereavement context.ObjectiveTo examine whether GF-CBT group is noninferior to GF-CBT individual in reducing PGD symptoms in older adults.Design, Setting, and ParticipantsEnrollment and data collection for this noninferiority randomized clinical trial took place from April 2021 to May 2025. Participants were randomized 1:1 to GF-CBT group and GF-CBT individual and followed up with until 6 months posttreatment. Recruitment and treatment were done in a naturalistic clinical practice. Participants included older bereaved adults (65 years or older) with clinically relevant levels of PGD, posttraumatic stress disorder (PTSD), depression, and/or anxiety based on established cutoffs on self-report questionnaires. These data were analyzed from June 2025 through August 2025.InterventionsGF-CBT group and GF-CBT individual consisted of 12 weekly sessions (duration: 2 hours vs 1 hour), including the same intervention techniques in the same order (exposure, cognitive restructuring, and behavioral activation).Main outcomes and measuresOutcomes were measured at pretreatment, posttreatment, 3-month follow-up, and 6-month follow-up as the primary end point. The primary outcome was PGD symptoms measured with the Prolonged Grief-13 questionnaire. Secondary outcomes included symptoms of PTSD, depression, anxiety, loneliness, social support, functional impairment, quality of life, and well-being.ResultsParticipants (N = 113; mean [SD] age, 71.58 [5.86] years; 92 female [81.4%], 20 male [17.7%], and 1 person [.09%] had missing information on gender) were randomized to GF-CBT group (n = 56) or GF-CBT individual (n = 57). Mixed linear models on the intention-to-treat sample showed that both formats yielded statistically significant large reductions in PGD symptoms over time (GF-CBT group: d = 1.74; GF-CBT individual: d = 1.46). GF-CBT group was noninferior compared with GF-CBT individual (d = 0.09; 95% CI, -0.06 to 0.25) at 6-month follow-up. The noninferiority of GF-CBT group was evidenced for all secondary outcomes. Dropout rates were 23% (GF-CBT group) vs 19% (GF-CBT individual).Conclusions and relevanceIn this study, GF-CBT group was noninferior to GF-CBT individual at 6-month follow-up in reducing PGD symptoms, but also symptoms of PTSD, depression, and anxiety. Both formats had large effects on symptoms over time and appear to be relevant treatment formats for older adults with symptoms of PGD and other disorders post loss.Trial RegistrationClinicalTrials.gov Identifier: NCT04694807.
{"title":"Group Vs Individual Grief-Focused Cognitive Behavioral Therapy for Older Adults: A Randomized Clinical Trial.","authors":"Katrine Komischke,Paul A Boelen,Fiona Maccallum,Maja O'Connor","doi":"10.1001/jamapsychiatry.2025.4106","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.4106","url":null,"abstract":"ImportanceGrief-focused cognitive behavioral therapies (GF-CBTs) are found effective in treating prolonged grief disorder (PGD), but the relative efficacy of different delivery formats is unknown. While evidence for individual GF-CBT (GF-CBT individual) is well established, evidence for group GF-CBT (GF-CBT group) is scarce. However, the group format holds possible advantages in a bereavement context.ObjectiveTo examine whether GF-CBT group is noninferior to GF-CBT individual in reducing PGD symptoms in older adults.Design, Setting, and ParticipantsEnrollment and data collection for this noninferiority randomized clinical trial took place from April 2021 to May 2025. Participants were randomized 1:1 to GF-CBT group and GF-CBT individual and followed up with until 6 months posttreatment. Recruitment and treatment were done in a naturalistic clinical practice. Participants included older bereaved adults (65 years or older) with clinically relevant levels of PGD, posttraumatic stress disorder (PTSD), depression, and/or anxiety based on established cutoffs on self-report questionnaires. These data were analyzed from June 2025 through August 2025.InterventionsGF-CBT group and GF-CBT individual consisted of 12 weekly sessions (duration: 2 hours vs 1 hour), including the same intervention techniques in the same order (exposure, cognitive restructuring, and behavioral activation).Main outcomes and measuresOutcomes were measured at pretreatment, posttreatment, 3-month follow-up, and 6-month follow-up as the primary end point. The primary outcome was PGD symptoms measured with the Prolonged Grief-13 questionnaire. Secondary outcomes included symptoms of PTSD, depression, anxiety, loneliness, social support, functional impairment, quality of life, and well-being.ResultsParticipants (N = 113; mean [SD] age, 71.58 [5.86] years; 92 female [81.4%], 20 male [17.7%], and 1 person [.09%] had missing information on gender) were randomized to GF-CBT group (n = 56) or GF-CBT individual (n = 57). Mixed linear models on the intention-to-treat sample showed that both formats yielded statistically significant large reductions in PGD symptoms over time (GF-CBT group: d = 1.74; GF-CBT individual: d = 1.46). GF-CBT group was noninferior compared with GF-CBT individual (d = 0.09; 95% CI, -0.06 to 0.25) at 6-month follow-up. The noninferiority of GF-CBT group was evidenced for all secondary outcomes. Dropout rates were 23% (GF-CBT group) vs 19% (GF-CBT individual).Conclusions and relevanceIn this study, GF-CBT group was noninferior to GF-CBT individual at 6-month follow-up in reducing PGD symptoms, but also symptoms of PTSD, depression, and anxiety. Both formats had large effects on symptoms over time and appear to be relevant treatment formats for older adults with symptoms of PGD and other disorders post loss.Trial RegistrationClinicalTrials.gov Identifier: NCT04694807.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"187 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145961301","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}
Pub Date : 2026-01-07DOI: 10.1001/jamapsychiatry.2025.4080
Dongmei Zhi,Sofia A Perdomo,Liam R Arteaga,Dylan E Hughes,Erin C Dunn,Phil H Lee,A Eden Evins,Harrison T Reeder,Scott E Hadland,Alysa E Doyle,Jacqueline A Clauss,Jing Sui,Joshua L Roffman,Jodi M Gilman
ImportanceAdverse prenatal exposures (APEs) often co-occur and independently associate with risk for childhood psychopathology. Whether exposure to multiple APEs is associated with persistent clinical effects through adolescence or underlying changes in brain maturation remains uncertain.ObjectiveTo evaluate longitudinal associations among cumulative APE burden, risk for psychopathology, and age-related cortical thinning in adolescents.Design, Setting, and ParticipantsThis cohort study analyzed 4-year follow-up data from the Adolescent Brain Cognitive Development (ABCD) Study, which enrolled 11 868 youth aged 9 to 10 years beginning in 2016. Sibling-comparison analysis was performed on 414 nonadopted sibling pairs with discordant APEs. Statistical analysis occurred from March to September 2025.ExposuresCumulative APE burden was calculated by summing 6 binary prenatal exposures that independently associated with psychopathology at baseline: unplanned pregnancy; early maternal prenatal alcohol, tobacco, or marijuana use; complicated pregnancy; and complicated birth.Main Outcomes and MeasuresOutcomes included annual Child Behavior Checklist (CBCL) scores of dimensional psychopathology, using both continuous and thresholded outcomes and biennial cortical thickness measures from structural magnetic resonance imaging, analyzed using linear mixed-effects models.ResultsOf 8515 singleton children (mean [SD] baseline age, 9.9 [0.6] years; 4460 male [52.4%]), 6644 (78%) were exposed to at least 1 APE. Multiple APEs persistently and dose-dependently associated with increased odds of clinically significant psychopathology (CBCL total problems: exposure to 1 APE [odds ratio (OR), 2.01; 95% CI, 1.28-3.16; corrected P = .006], 2 APEs [OR, 3.82; 95% CI, 2.39-6.11; corrected P <.001], and 3 or more APEs [OR, 6.75; 95% CI, 4.14-11.02; corrected P <.001]). Associations of APEs with attention-deficit/hyperactivity disorder symptoms attenuated over time (interaction: F = 13.51; corrected P = 7.13 × 10-8), whereas those with depressive symptoms potentiated (interaction: F = 5.82; corrected P = .002). Greater APE burden associated with accelerated age-related cortical thinning in 36 of 68 cortical regions (interaction for the right middle temporal cortex: F = 8.89; corrected P < .001). Siblings with more exposures demonstrated persistently higher CBCL total problems (t = 2.25; P = .03) and accelerated cortical thinning in 5 of the 36 regions implicated in the larger sample.Conclusions and RelevanceResults of this cohort study show that multiple prenatal adversities were associated with altered developmental trajectories of psychopathology and cortical maturation into midadolescence. These findings highlight the importance of fetal programming to mental health across life course and the need for additional study of risk and resiliency-conferring factors in utero.
{"title":"Prenatal Adversities and Risk of Persistent Youth Psychopathology and Altered Cortical Thinning.","authors":"Dongmei Zhi,Sofia A Perdomo,Liam R Arteaga,Dylan E Hughes,Erin C Dunn,Phil H Lee,A Eden Evins,Harrison T Reeder,Scott E Hadland,Alysa E Doyle,Jacqueline A Clauss,Jing Sui,Joshua L Roffman,Jodi M Gilman","doi":"10.1001/jamapsychiatry.2025.4080","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.4080","url":null,"abstract":"ImportanceAdverse prenatal exposures (APEs) often co-occur and independently associate with risk for childhood psychopathology. Whether exposure to multiple APEs is associated with persistent clinical effects through adolescence or underlying changes in brain maturation remains uncertain.ObjectiveTo evaluate longitudinal associations among cumulative APE burden, risk for psychopathology, and age-related cortical thinning in adolescents.Design, Setting, and ParticipantsThis cohort study analyzed 4-year follow-up data from the Adolescent Brain Cognitive Development (ABCD) Study, which enrolled 11 868 youth aged 9 to 10 years beginning in 2016. Sibling-comparison analysis was performed on 414 nonadopted sibling pairs with discordant APEs. Statistical analysis occurred from March to September 2025.ExposuresCumulative APE burden was calculated by summing 6 binary prenatal exposures that independently associated with psychopathology at baseline: unplanned pregnancy; early maternal prenatal alcohol, tobacco, or marijuana use; complicated pregnancy; and complicated birth.Main Outcomes and MeasuresOutcomes included annual Child Behavior Checklist (CBCL) scores of dimensional psychopathology, using both continuous and thresholded outcomes and biennial cortical thickness measures from structural magnetic resonance imaging, analyzed using linear mixed-effects models.ResultsOf 8515 singleton children (mean [SD] baseline age, 9.9 [0.6] years; 4460 male [52.4%]), 6644 (78%) were exposed to at least 1 APE. Multiple APEs persistently and dose-dependently associated with increased odds of clinically significant psychopathology (CBCL total problems: exposure to 1 APE [odds ratio (OR), 2.01; 95% CI, 1.28-3.16; corrected P = .006], 2 APEs [OR, 3.82; 95% CI, 2.39-6.11; corrected P <.001], and 3 or more APEs [OR, 6.75; 95% CI, 4.14-11.02; corrected P <.001]). Associations of APEs with attention-deficit/hyperactivity disorder symptoms attenuated over time (interaction: F = 13.51; corrected P = 7.13 × 10-8), whereas those with depressive symptoms potentiated (interaction: F = 5.82; corrected P = .002). Greater APE burden associated with accelerated age-related cortical thinning in 36 of 68 cortical regions (interaction for the right middle temporal cortex: F = 8.89; corrected P < .001). Siblings with more exposures demonstrated persistently higher CBCL total problems (t = 2.25; P = .03) and accelerated cortical thinning in 5 of the 36 regions implicated in the larger sample.Conclusions and RelevanceResults of this cohort study show that multiple prenatal adversities were associated with altered developmental trajectories of psychopathology and cortical maturation into midadolescence. These findings highlight the importance of fetal programming to mental health across life course and the need for additional study of risk and resiliency-conferring factors in utero.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"23 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907864","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}
Pub Date : 2026-01-07DOI: 10.1001/jamapsychiatry.2025.4103
Julia Bondar,Lucas Primo de Carvalho Alves
{"title":"Balancing Surrogate Efficacy and Psychiatric Safety in the HISTORI Trial.","authors":"Julia Bondar,Lucas Primo de Carvalho Alves","doi":"10.1001/jamapsychiatry.2025.4103","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.4103","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"45 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907848","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}
ImportanceOpioid withdrawal involves sympathetic hyperactivity and reduced parasympathetic tone, which standard pharmacological treatments may not adequately address, contributing to relapse vulnerability.ObjectiveTo evaluate yoga as adjuvant therapy to accelerate opioid withdrawal recovery and assess its impact on heart rate variability, anxiety, sleep, and pain.Design, Setting, and ParticipantsThis 2-arm, early-stage randomized clinical trial was conducted at an addiction medicine inpatient ward in India from April 30, 2023 to March 31, 2024. The outcome assessors and data analyst were blinded to group allocation. Participants included adults aged 18 to 50 years with opioid use disorder experiencing mild to moderate withdrawal symptoms (Clinical Opiate Withdrawal Scale [COWS] scores 4-24). Exclusion criteria included severe withdrawal, neurological conditions affecting autonomic function, severe psychiatric conditions, and recent yoga training. Of 68 individuals screened, 59 were randomized (30 yoga and 29 control participants).InterventionParticipants in the yoga group received 10 supervised 45-minute sessions during 14 days alongside standard buprenorphine treatment, including relaxation practices, postures, breathing techniques, and guided relaxation. Participants in the control group received standard buprenorphine treatment only.Main Outcomes and MeasuresCo-primary outcomes included time to withdrawal stabilization (COWS score <4) and heart rate variability parameters. Secondary outcomes included anxiety (Hamilton Anxiety Rating Scale), sleep latency, and pain scores. Assessments were conducted at baseline (day 1) and day 15.ResultsFifty-nine participants (59 male [100%]; mean [SD] age, 25.6 [3.9] years) completed intent-to-treat analysis. Participants in the yoga group recovered faster than those in the control group (hazard ratio [HR], 4.40; 95% CI, 2.40-8.07; P < .001), with a median stabilization time of 5 days (95% CI, 4-6 days) for those in the yoga group vs 9 days (95% CI, 7-13 days) for the control group. Participants in the yoga group showed superior heart rate variability improvements with large effects on low frequency (LF) power (ω2 = 0.16), high frequency (HF) power (ω2 = 0.14), and LF/HF ratio (ω2 = 0.12); all effects were statistically significant (P < .001). Mediation analysis showed that increases in parasympathetic activity accounted for 23% of the treatment effect (indirect HR, 1.38; 95% CI, 1.10-2.03). Anxiety reduction was significantly greater among those in the yoga group (ω2 = 0.28; P < .001), with moderate improvements in sleep latency (a 61-minute reduction; P = .008) and pain (P = .004).Conclusions and RelevanceIn this randomized clinical trial, yoga significantly accelerated opioid withdrawal recovery and improved autonomic regulation, anxiety, sleep, and pain. These findings support integrating yoga into withdrawal protocols as a neurobiologically informed intervention addressing core regulatory processes beyon
{"title":"Yoga for Opioid Withdrawal and Autonomic Regulation: A Randomized Clinical Trial.","authors":"Suddala Goutham,Hemant Bhargav,Bharath Holla,Jayant Mahadevan,Ravindra P Nagendra,Nishitha Jasti,Venkata Lakshmi Narasimha,Urvakhsh Meherwan Mehta,Shivarama Varambally,Ganesan Venkatasubramanian,Prabhat Chand,Bangalore Nanjundiah Gangadhar,Kevin P Hill,Matcheri Keshavan,Pratima Murthy","doi":"10.1001/jamapsychiatry.2025.3863","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.3863","url":null,"abstract":"ImportanceOpioid withdrawal involves sympathetic hyperactivity and reduced parasympathetic tone, which standard pharmacological treatments may not adequately address, contributing to relapse vulnerability.ObjectiveTo evaluate yoga as adjuvant therapy to accelerate opioid withdrawal recovery and assess its impact on heart rate variability, anxiety, sleep, and pain.Design, Setting, and ParticipantsThis 2-arm, early-stage randomized clinical trial was conducted at an addiction medicine inpatient ward in India from April 30, 2023 to March 31, 2024. The outcome assessors and data analyst were blinded to group allocation. Participants included adults aged 18 to 50 years with opioid use disorder experiencing mild to moderate withdrawal symptoms (Clinical Opiate Withdrawal Scale [COWS] scores 4-24). Exclusion criteria included severe withdrawal, neurological conditions affecting autonomic function, severe psychiatric conditions, and recent yoga training. Of 68 individuals screened, 59 were randomized (30 yoga and 29 control participants).InterventionParticipants in the yoga group received 10 supervised 45-minute sessions during 14 days alongside standard buprenorphine treatment, including relaxation practices, postures, breathing techniques, and guided relaxation. Participants in the control group received standard buprenorphine treatment only.Main Outcomes and MeasuresCo-primary outcomes included time to withdrawal stabilization (COWS score <4) and heart rate variability parameters. Secondary outcomes included anxiety (Hamilton Anxiety Rating Scale), sleep latency, and pain scores. Assessments were conducted at baseline (day 1) and day 15.ResultsFifty-nine participants (59 male [100%]; mean [SD] age, 25.6 [3.9] years) completed intent-to-treat analysis. Participants in the yoga group recovered faster than those in the control group (hazard ratio [HR], 4.40; 95% CI, 2.40-8.07; P < .001), with a median stabilization time of 5 days (95% CI, 4-6 days) for those in the yoga group vs 9 days (95% CI, 7-13 days) for the control group. Participants in the yoga group showed superior heart rate variability improvements with large effects on low frequency (LF) power (ω2 = 0.16), high frequency (HF) power (ω2 = 0.14), and LF/HF ratio (ω2 = 0.12); all effects were statistically significant (P < .001). Mediation analysis showed that increases in parasympathetic activity accounted for 23% of the treatment effect (indirect HR, 1.38; 95% CI, 1.10-2.03). Anxiety reduction was significantly greater among those in the yoga group (ω2 = 0.28; P < .001), with moderate improvements in sleep latency (a 61-minute reduction; P = .008) and pain (P = .004).Conclusions and RelevanceIn this randomized clinical trial, yoga significantly accelerated opioid withdrawal recovery and improved autonomic regulation, anxiety, sleep, and pain. These findings support integrating yoga into withdrawal protocols as a neurobiologically informed intervention addressing core regulatory processes beyon","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"29 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907865","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}
Pub Date : 2026-01-07DOI: 10.1001/jamapsychiatry.2025.4091
Luis F Rivera-Chávez,Daniela González-Sangabriel,Luz González-Manríquez,Tomás Moncada-Habib,Pablo León-Ortiz,Melanie Malacara,Francisco Reyes-Madrigal,Camilo de la Fuente-Sandoval
ImportanceEvidence suggests that elevated glutamate levels in the medial prefrontal cortex may be associated with the illness stage, but little is known about whether these effects occur in the absence of antipsychotic treatment.ObjectiveTo evaluate differences in glutamate levels in treatment-naive individuals with psychosis on the schizophrenia spectrum at different stages of the illness.Design, Setting, and ParticipantsThis cross-sectional study uses proton magnetic resonance spectroscopy in the medial prefrontal cortex of individuals experiencing their first episode of nonaffective psychosis, individuals with chronic schizophrenia, and matched controls at inpatient and outpatient services of the Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico, from November 2017 to July 2025. Data were analyzed from January 28, 2025, to August 8, 2025.ExposureProton magnetic resonance spectroscopy.Main Outcomes and MeasuresThe primary outcome was glutamate levels and scores measured on the Positive and Negative Syndrome Scale for Schizophrenia and the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery.ResultsThis cross-sectional study included a total of 181 individuals (65 with first-episode psychosis [FEP], 42 with chronic schizophrenia, and 74 age- and sex-matched healthy controls). Data from 38 participants (14 with FEP, 10 with schizophrenia, and 14 controls) were rejected from all analyses due to excessive movement or poor spectral quality, leaving 83 participants and 60 controls. The mean (SD) age was 25.9 (7.2) years for individuals with FEP, 38.0 (14.5) years for those with chronic schizophrenia, and 30.4 (11.5) years for controls. Sex distribution did not differ (34 male individuals with FEP [67.0%]; 20 male individuals with chronic schizophrenia [62.5%]; and 33 male controls [55.0%]; P = .44). Glutamate levels differed among the 3 groups (F2,136 = 7.5; P = .001). Post hoc pairwise comparisons revealed higher glutamate levels in the FEP group compared with both the chronic schizophrenia group (P = .003; Cohen d = 0.69) and the control group (P = .008; Cohen d = 0.83). There were no significant differences in glutamate levels between the chronic schizophrenia group and the control group (P > .99). Higher glutamate levels were associated with lower verbal (ρ = -0.29; P = .04) and visual learning scores (ρ = -0.29; P = .04) in the FEP group.Conclusions and RelevanceThese findings suggest that the differences in glutamate levels may indicate that these alterations occur primarily in the early stages of the disease. The results of this study have implications for resuming clinical trials with targeted metabotropic glutamate receptor 2/3 agonists, taking into account both the disease phase and the glutamatergic alterations measured by magnetic resonance imaging.
重要证据表明，内侧前额叶皮层谷氨酸水平升高可能与疾病阶段有关，但很少有人知道这些影响是否发生在没有抗精神病药物治疗的情况下。目的评价未接受治疗的精神分裂症患者在不同病程阶段谷氨酸水平的差异。设计、环境和参与者本横断面研究在2017年11月至2025年7月期间，在墨西哥墨西哥城国立研究所Neurología y Neurocirugía的住院和门诊服务中，对首次经历非情感性精神病发作的个体、慢性精神分裂症患者和匹配对照进行了质子磁共振波谱检测。数据分析时间为2025年1月28日至2025年8月8日。质子磁共振光谱学。主要结局和测量主要结局为谷氨酸水平和精神分裂症阳性和阴性综合征量表的评分，以及改善精神分裂症共识认知电池认知的测量和治疗研究。结果本横断面研究共纳入181人（65例首发精神病，42例慢性精神分裂症，74例年龄和性别匹配的健康对照）。38名参与者（14名FEP患者，10名精神分裂症患者和14名对照组）的数据因过度运动或光谱质量差而被所有分析拒绝，剩下83名参与者和60名对照组。FEP患者的平均（SD）年龄为25.9（7.2）岁，慢性精神分裂症患者的平均（SD）年龄为38.0（14.5）岁，对照组为30.4（11.5）岁。性别分布无差异（男性FEP患者34例[67.0%]，男性慢性精神分裂症患者20例[62.5%]，男性对照组33例[55.0%],P = 0.44）。谷氨酸水平在三组间存在差异（f2136 = 7.5; P = 0.001）。事后两两比较显示，FEP组的谷氨酸水平高于慢性精神分裂症组（P = 0.003; Cohen d = 0.69）和对照组（P = 0.008; Cohen d = 0.83）。慢性精神分裂症组与对照组间谷氨酸水平差异无统计学意义（P < 0.05）。较高的谷氨酸水平与较低的言语水平相关(ρ = -0.29; P =。04)和视觉学习分数(ρ = -0.29; P =。04) FEP组。结论和相关性这些发现提示谷氨酸水平的差异可能表明这些改变主要发生在疾病的早期阶段。考虑到疾病阶段和磁共振成像测量的谷氨酸能改变，本研究的结果对恢复靶向代谢型谷氨酸受体2/3激动剂的临床试验具有重要意义。
{"title":"Glutamate Levels in Medial Prefrontal Cortex According to Illness Phase of Never-Medicated Individuals With Psychosis.","authors":"Luis F Rivera-Chávez,Daniela González-Sangabriel,Luz González-Manríquez,Tomás Moncada-Habib,Pablo León-Ortiz,Melanie Malacara,Francisco Reyes-Madrigal,Camilo de la Fuente-Sandoval","doi":"10.1001/jamapsychiatry.2025.4091","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.4091","url":null,"abstract":"ImportanceEvidence suggests that elevated glutamate levels in the medial prefrontal cortex may be associated with the illness stage, but little is known about whether these effects occur in the absence of antipsychotic treatment.ObjectiveTo evaluate differences in glutamate levels in treatment-naive individuals with psychosis on the schizophrenia spectrum at different stages of the illness.Design, Setting, and ParticipantsThis cross-sectional study uses proton magnetic resonance spectroscopy in the medial prefrontal cortex of individuals experiencing their first episode of nonaffective psychosis, individuals with chronic schizophrenia, and matched controls at inpatient and outpatient services of the Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico, from November 2017 to July 2025. Data were analyzed from January 28, 2025, to August 8, 2025.ExposureProton magnetic resonance spectroscopy.Main Outcomes and MeasuresThe primary outcome was glutamate levels and scores measured on the Positive and Negative Syndrome Scale for Schizophrenia and the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery.ResultsThis cross-sectional study included a total of 181 individuals (65 with first-episode psychosis [FEP], 42 with chronic schizophrenia, and 74 age- and sex-matched healthy controls). Data from 38 participants (14 with FEP, 10 with schizophrenia, and 14 controls) were rejected from all analyses due to excessive movement or poor spectral quality, leaving 83 participants and 60 controls. The mean (SD) age was 25.9 (7.2) years for individuals with FEP, 38.0 (14.5) years for those with chronic schizophrenia, and 30.4 (11.5) years for controls. Sex distribution did not differ (34 male individuals with FEP [67.0%]; 20 male individuals with chronic schizophrenia [62.5%]; and 33 male controls [55.0%]; P = .44). Glutamate levels differed among the 3 groups (F2,136 = 7.5; P = .001). Post hoc pairwise comparisons revealed higher glutamate levels in the FEP group compared with both the chronic schizophrenia group (P = .003; Cohen d = 0.69) and the control group (P = .008; Cohen d = 0.83). There were no significant differences in glutamate levels between the chronic schizophrenia group and the control group (P > .99). Higher glutamate levels were associated with lower verbal (ρ = -0.29; P = .04) and visual learning scores (ρ = -0.29; P = .04) in the FEP group.Conclusions and RelevanceThese findings suggest that the differences in glutamate levels may indicate that these alterations occur primarily in the early stages of the disease. The results of this study have implications for resuming clinical trials with targeted metabotropic glutamate receptor 2/3 agonists, taking into account both the disease phase and the glutamatergic alterations measured by magnetic resonance imaging.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"2 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907866","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}
Pub Date : 2026-01-01DOI: 10.1001/jamapsychiatry.2025.3242
Ioana A Cristea, Martin Plöderl, Florian Naudet
{"title":"Esketamine for Treatment-Resistant Depression.","authors":"Ioana A Cristea, Martin Plöderl, Florian Naudet","doi":"10.1001/jamapsychiatry.2025.3242","DOIUrl":"10.1001/jamapsychiatry.2025.3242","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":"103"},"PeriodicalIF":17.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145444696","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}
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