Pub Date : 2025-10-08DOI: 10.1001/jamapsychiatry.2025.2539
Andrew S. Hyatt, Michael William Flores, Julie Johnson, Danta Bien-Aime, A. Eden Evins, Dost Öngür, Benjamin Lê Cook
ImportanceMany individuals can use cannabis without harm, but individuals with psychosis are particularly vulnerable to negative effects from cannabis. No studies to date have investigated how recreational cannabis legalization (RCL) affects cannabis use in individuals with psychosis.ObjectiveTo assess impacts of RCL in cannabis use among individuals who have ever been diagnosed with a psychotic illness or episode in the US.Design, Setting, and ParticipantsThis study used data from 2014 to 2022 on state-level RCL with 5 years of follow-up from the Population Assessment of Tobacco and Health, a nationally representative longitudinal cohort study of 1856 adults aged 18 years and older in the US. The study sample consisted of individuals with a lifetime history of psychosis. Data were analyzed between January and June 2025.Main Outcomes and MeasuresPercentage point (pp) changes in 30-day use of cannabis after RCL compared with control states using difference-in-differences methods.ResultsThe study sample consisted of 1856 individuals, with a mean age of 36.6 years (SD, 14.8 years) contributing 7465 responses, and was 50.2% White, 58.2% female, and had a 30-day cannabis-use rate of 31.8%. Individuals with psychosis in RCL states significantly increased their 30-day cannabis use by 9.53 pp (95% CI, 3.05-16.00 pp; P = .004), with sensitivity analyses showing significant estimates after retail outlets opened but not before, and no changes in higher frequency use.Conclusions and RelevanceIn this study, individuals with psychosis reported a large increase in current cannabis use following legalization and commercialization of cannabis in their state, and by larger amounts than previously reported estimates of the general population. Given how cannabis can negatively affect illness course and health service utilization in individuals with psychosis, these results should be considered by regulators designing policies around taxation, potency, advertising, and health warnings.
许多人可以使用大麻而不会受到伤害，但精神病患者特别容易受到大麻的负面影响。迄今为止还没有研究调查娱乐性大麻合法化（RCL）如何影响精神病患者的大麻使用。目的评估在美国曾被诊断为精神病或发作的个体中，RCL对大麻使用的影响。设计、环境和参与者本研究使用了2014年至2022年的国家级RCL数据，并对烟草与健康人口评估进行了5年的随访，这是一项具有全国代表性的纵向队列研究，研究对象为美国1856名18岁及以上的成年人。研究样本包括有终生精神病病史的个体。研究人员分析了2025年1月至6月的数据。主要结果和测量方法采用差异中差异方法与对照状态比较，RCL后30天大麻使用百分比（pp）的变化。结果样本共1856人，平均年龄36.6岁（SD 14.8岁），共有7465人回复，其中白人50.2%，女性58.2%，30天大麻使用率为31.8%。RCL州精神病患者的30天大麻使用量显著增加了9.53 pp (95% CI, 3.05-16.00 pp; P = 0.004)，敏感性分析显示零售店开业后有显著的估计，但之前没有，使用频率没有变化。结论和相关性在这项研究中，精神病患者报告说，在大麻在其所在州合法化和商业化后，目前大麻的使用量大幅增加，而且比以前报道的一般人群的估计量要大。鉴于大麻对精神病患者病程和卫生服务利用的负面影响，监管机构在制定税收、效力、广告和健康警告等政策时应考虑这些结果。
{"title":"Cannabis Use Among Individuals With Psychosis After State-Level Commercial Cannabis Legalization","authors":"Andrew S. Hyatt, Michael William Flores, Julie Johnson, Danta Bien-Aime, A. Eden Evins, Dost Öngür, Benjamin Lê Cook","doi":"10.1001/jamapsychiatry.2025.2539","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.2539","url":null,"abstract":"ImportanceMany individuals can use cannabis without harm, but individuals with psychosis are particularly vulnerable to negative effects from cannabis. No studies to date have investigated how recreational cannabis legalization (RCL) affects cannabis use in individuals with psychosis.ObjectiveTo assess impacts of RCL in cannabis use among individuals who have ever been diagnosed with a psychotic illness or episode in the US.Design, Setting, and ParticipantsThis study used data from 2014 to 2022 on state-level RCL with 5 years of follow-up from the Population Assessment of Tobacco and Health, a nationally representative longitudinal cohort study of 1856 adults aged 18 years and older in the US. The study sample consisted of individuals with a lifetime history of psychosis. Data were analyzed between January and June 2025.Main Outcomes and MeasuresPercentage point (pp) changes in 30-day use of cannabis after RCL compared with control states using difference-in-differences methods.ResultsThe study sample consisted of 1856 individuals, with a mean age of 36.6 years (SD, 14.8 years) contributing 7465 responses, and was 50.2% White, 58.2% female, and had a 30-day cannabis-use rate of 31.8%. Individuals with psychosis in RCL states significantly increased their 30-day cannabis use by 9.53 pp (95% CI, 3.05-16.00 pp; <jats:italic>P</jats:italic> = .004), with sensitivity analyses showing significant estimates after retail outlets opened but not before, and no changes in higher frequency use.Conclusions and RelevanceIn this study, individuals with psychosis reported a large increase in current cannabis use following legalization and commercialization of cannabis in their state, and by larger amounts than previously reported estimates of the general population. Given how cannabis can negatively affect illness course and health service utilization in individuals with psychosis, these results should be considered by regulators designing policies around taxation, potency, advertising, and health warnings.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"11 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241508","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 : 2025-10-08DOI: 10.1001/jamapsychiatry.2025.2850
Craig J. Bryan, Lauren R. Khazem, Justin C. Baker, Lily A. Brown, Daniel J. Taylor, Kristi E. Pruiksma, Ron Acierno, Jayme G. Larick, Brian R. W. Baucom, Eric L. Garland, M. David Rudd
ImportanceUS military personnel and veterans have higher rates of suicide than the general population. Previous trials support the efficacy of brief cognitive behavioral therapy (BCBT) for reducing suicide attempts among military personnel compared with treatment as usual, and replication of these findings is needed.ObjectiveTo test the efficacy of BCBT for reducing suicide attempts and suicidal ideation among high-risk military personnel and veterans.Design, Setting, and ParticipantsThis was a 2-arm, parallel randomized clinical trial comparing BCBT with present-centered therapy (PCT), conducted from 2020 to 2025. The setting was 3 US-based outpatient psychiatric clinics and included US military personnel and veterans reporting suicidal ideation during the past week and/or suicidal behavior during the past month who were either self-referred or referred by their mental health clinicians.InterventionsParticipants were randomly assigned to either BCBT, a psychotherapy that teaches emotion regulation skills, or PCT, a problem-solving psychotherapy, using a computerized algorithm with stratification for sex and number of prior suicide attempts.Main Outcomes and MeasuresThe primary outcome was suicide attempt, assessed with the Self-Injurious Thoughts and Behaviors Interview–Revised.ResultsOf 154 individuals assessed for eligibility, 108 (mean [SD] age, 32.8 [12.8] years; 79 male [73.1%]) were enrolled. Fewer patients receiving BCBT (n = 2, estimated proportion = 5.6%) than PCT (n = 8, estimated proportion = 27.9%) attempted suicide during follow-up. Mean time to first suicide attempt was 638.6 (90% CI, 557.8-719.3) days in the PCT group vs 755.9 (90% CI, 715.1-796.8) days in the BCBT group (log-rank χ21 = 3.6; P = .03). BCBT significantly reduced the risk of any suicide attempt (hazard ratio [HR], 0.25; 90% CI, 0.07-0.90; P = .04) as well as the rate of follow-up suicide attempts (0.06 vs 0.18 attempts per participant-year, risk ratio, 0.24; 90% CI, 0.08-0.70; P = .02). Suicidal ideation significantly decreased in both groups (F8,264 = 7.2, P &lt; .001) with no differences between groups (F8,266 = 0.2; P = .49).Conclusions and RelevanceThis randomized clinical trial found that BCBT reduced suicide attempts among US military personnel and veterans reporting recent suicidal ideation and/or suicidal behaviors compared with an active comparator. These results replicate earlier findings.Trial RegistrationClinicalTrials.gov Identifier: NCT03769259
重要的是，美国军人和退伍军人的自杀率高于普通人群。先前的试验支持短期认知行为疗法（bbct）在减少军人自杀企图方面的效果，与常规治疗相比，这些发现还需要复制。目的探讨bbct对降低高危军人和退伍军人自杀企图和自杀意念的效果。设计、环境和参与者：这是一项2组平行随机临床试验，比较bbct和以现在为中心的治疗（PCT），从2020年到2025年进行。研究对象为美国3家精神病门诊诊所，包括在过去一周内有自杀意念和/或在过去一个月有自杀行为的美国军人和退伍军人，他们要么是自我推荐的，要么是由心理健康临床医生推荐的。干预措施参与者被随机分配到BCBT（一种教授情绪调节技巧的心理治疗）和PCT（一种解决问题的心理治疗），使用计算机化算法对性别和之前的自杀企图进行分层。主要结果和测量主要结果是自杀企图，用自我伤害思想和行为访谈-修订版进行评估。结果154例入选者中，108例（平均[SD]年龄32.8[12.8]岁，男性79例[73.1%]）入选。随访期间，接受BCBT的患者（n = 2，估计比例= 5.6%）比接受PCT的患者（n = 8，估计比例= 27.9%）自杀未遂。PCT组至首次自杀企图的平均时间为638.6 （90% CI, 557.8-719.3）天，而BCBT组为755.9 （90% CI, 715.1-796.8）天（log-rank χ21 = 3.6; P = 0.03）。bbct显著降低了任何自杀企图的风险（风险比[HR]， 0.25; 90% CI, 0.07-0.90; P = 0.04）以及随访自杀企图率（每参与者年0.06 vs 0.18次，风险比，0.24;90% CI, 0.08-0.70; P = 0.02）。两组患者自杀意念均显著降低（f8264 = 7.2, P <）。001)，组间差异无统计学意义（f8266 = 0.2; P = 0.49）。结论和相关性这项随机临床试验发现，与积极对照相比，bbct减少了美国军人和退伍军人近期报告自杀意念和/或自杀行为的自杀企图。这些结果重复了早期的发现。临床试验注册号：NCT03769259
{"title":"Brief Cognitive Behavioral Therapy for Suicidal Military Personnel and Veterans","authors":"Craig J. Bryan, Lauren R. Khazem, Justin C. Baker, Lily A. Brown, Daniel J. Taylor, Kristi E. Pruiksma, Ron Acierno, Jayme G. Larick, Brian R. W. Baucom, Eric L. Garland, M. David Rudd","doi":"10.1001/jamapsychiatry.2025.2850","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.2850","url":null,"abstract":"ImportanceUS military personnel and veterans have higher rates of suicide than the general population. Previous trials support the efficacy of brief cognitive behavioral therapy (BCBT) for reducing suicide attempts among military personnel compared with treatment as usual, and replication of these findings is needed.ObjectiveTo test the efficacy of BCBT for reducing suicide attempts and suicidal ideation among high-risk military personnel and veterans.Design, Setting, and ParticipantsThis was a 2-arm, parallel randomized clinical trial comparing BCBT with present-centered therapy (PCT), conducted from 2020 to 2025. The setting was 3 US-based outpatient psychiatric clinics and included US military personnel and veterans reporting suicidal ideation during the past week and/or suicidal behavior during the past month who were either self-referred or referred by their mental health clinicians.InterventionsParticipants were randomly assigned to either BCBT, a psychotherapy that teaches emotion regulation skills, or PCT, a problem-solving psychotherapy, using a computerized algorithm with stratification for sex and number of prior suicide attempts.Main Outcomes and MeasuresThe primary outcome was suicide attempt, assessed with the Self-Injurious Thoughts and Behaviors Interview–Revised.ResultsOf 154 individuals assessed for eligibility, 108 (mean [SD] age, 32.8 [12.8] years; 79 male [73.1%]) were enrolled. Fewer patients receiving BCBT (n = 2, estimated proportion = 5.6%) than PCT (n = 8, estimated proportion = 27.9%) attempted suicide during follow-up. Mean time to first suicide attempt was 638.6 (90% CI, 557.8-719.3) days in the PCT group vs 755.9 (90% CI, 715.1-796.8) days in the BCBT group (log-rank χ<jats:sup>2</jats:sup><jats:sub>1</jats:sub> = 3.6; <jats:italic>P</jats:italic> = .03). BCBT significantly reduced the risk of any suicide attempt (hazard ratio [HR], 0.25; 90% CI, 0.07-0.90; <jats:italic>P</jats:italic> = .04) as well as the rate of follow-up suicide attempts (0.06 vs 0.18 attempts per participant-year, risk ratio, 0.24; 90% CI, 0.08-0.70; <jats:italic>P</jats:italic> = .02). Suicidal ideation significantly decreased in both groups (<jats:italic>F</jats:italic><jats:sub>8,264</jats:sub> = 7.2, <jats:italic>P</jats:italic> &amp;lt; .001) with no differences between groups (<jats:italic>F</jats:italic><jats:sub>8,266</jats:sub> = 0.2; <jats:italic>P</jats:italic> = .49).Conclusions and RelevanceThis randomized clinical trial found that BCBT reduced suicide attempts among US military personnel and veterans reporting recent suicidal ideation and/or suicidal behaviors compared with an active comparator. These results replicate earlier findings.Trial RegistrationClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"https://www.clinicaltrials.gov/study/NCT03769259\">NCT03769259</jats:ext-link>","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"24 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145241509","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 : 2025-10-08DOI: 10.1001/jamapsychiatry.2025.2710
Sameer A Sheth,John D Rolston,Wayne K Goodman,Nicole R Provenza
{"title":"Is Psychiatry Ready for Closed-Loop Invasive Neuromodulation?","authors":"Sameer A Sheth,John D Rolston,Wayne K Goodman,Nicole R Provenza","doi":"10.1001/jamapsychiatry.2025.2710","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.2710","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"128 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246561","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 Challenges of Muslim Populations Exposed to War and Discrimination.","authors":"Bilal Irfan,Aayesha Soni,Mohammed Al-Hasan,Belal Aldabbour","doi":"10.1001/jamapsychiatry.2025.2686","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.2686","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"20 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194531","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 : 2025-10-01DOI: 10.1001/jamapsychiatry.2025.2689
Andrea Johansson Capusan,Christal N Davis,Emelie Thern,Jürgen Rehm,Joel Gelernter,Henry R Kranzler,Markus Heilig
ImportanceAssociations among general intelligence (IQ), educational attainment (EA), and alcohol use disorder (AUD) are not well understood.ObjectiveTo examine the relationship between IQ, EA, and AUD risk.Design, Setting, and ParticipantsThe association between IQ and AUD risk was examined in a Swedish national conscription cohort. Potential causality was explored using mendelian randomization (MR) analyses, and the association of polygenic scores (PGS) for cognitive performance with AUD diagnosis was assessed. Participant data were obtained from cross-linked Swedish national registers, genome-wide association study (GWAS) summary statistics, and the US Yale-Penn cohort.ExposuresIQ and genetic variants associated with cognitive performance.Main Outcomes and MeasuresHazard ratios (HRs; time-to-event analyses) or odds ratios (ORs) for AUD.ResultsIncluded in this study was a national cohort of 645 488 males, born between 1950 and 1962, from the Swedish Military Conscription Register, of whom 573 855 individuals were included in this analysis. All individuals were aged 18 years at IQ assessment with no substance use disorder diagnosis at conscription, and mean (SD) follow-up time (SD) was 60.5 (7.9) years. Summary statistics from GWAS of cognitive performance (n = 257 481) and AUD (total = 753 248; cases = 113 325) in individuals of European-like genetic ancestry (EUR), with FinnGen AUD GWAS as a replication sample (total = 500 348; cases = 20 597), were used for MR analyses. PGS analyses were conducted using the data of EUR individuals from the Yale-Penn cohort (n = 5424). IQ at age 18 years was inversely associated with AUD risk in Swedish males (adjusted HR, 1.43; 95% CI, 1.40-1.47; P < .001), adjusting for parental substance use disorder, probands' psychiatric disorders, socioeconomic factors, and birth year strata. MR analyses suggested a causal relationship between lower cognitive performance and AUD risk (β [SE], 0.11 [0.02]; P = 2.6 × 10-12). The mediating role of EA differed between national contexts. Higher cognitive performance PGS were associated with reduced odds of AUD in Yale-Penn participants (OR, 0.83; 95% CI, 0.78-0.89).Conclusions and RelevanceIQ and cognitive performance have a significant but context-dependent association with AUD risk, highlighting the need for a better understanding of the interplay among genetic factors, cognitive traits, and sociocultural influences on AUD susceptibility.
{"title":"Measures of General Intelligence and Risk for Alcohol Use Disorder.","authors":"Andrea Johansson Capusan,Christal N Davis,Emelie Thern,Jürgen Rehm,Joel Gelernter,Henry R Kranzler,Markus Heilig","doi":"10.1001/jamapsychiatry.2025.2689","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.2689","url":null,"abstract":"ImportanceAssociations among general intelligence (IQ), educational attainment (EA), and alcohol use disorder (AUD) are not well understood.ObjectiveTo examine the relationship between IQ, EA, and AUD risk.Design, Setting, and ParticipantsThe association between IQ and AUD risk was examined in a Swedish national conscription cohort. Potential causality was explored using mendelian randomization (MR) analyses, and the association of polygenic scores (PGS) for cognitive performance with AUD diagnosis was assessed. Participant data were obtained from cross-linked Swedish national registers, genome-wide association study (GWAS) summary statistics, and the US Yale-Penn cohort.ExposuresIQ and genetic variants associated with cognitive performance.Main Outcomes and MeasuresHazard ratios (HRs; time-to-event analyses) or odds ratios (ORs) for AUD.ResultsIncluded in this study was a national cohort of 645 488 males, born between 1950 and 1962, from the Swedish Military Conscription Register, of whom 573 855 individuals were included in this analysis. All individuals were aged 18 years at IQ assessment with no substance use disorder diagnosis at conscription, and mean (SD) follow-up time (SD) was 60.5 (7.9) years. Summary statistics from GWAS of cognitive performance (n = 257 481) and AUD (total = 753 248; cases = 113 325) in individuals of European-like genetic ancestry (EUR), with FinnGen AUD GWAS as a replication sample (total = 500 348; cases = 20 597), were used for MR analyses. PGS analyses were conducted using the data of EUR individuals from the Yale-Penn cohort (n = 5424). IQ at age 18 years was inversely associated with AUD risk in Swedish males (adjusted HR, 1.43; 95% CI, 1.40-1.47; P < .001), adjusting for parental substance use disorder, probands' psychiatric disorders, socioeconomic factors, and birth year strata. MR analyses suggested a causal relationship between lower cognitive performance and AUD risk (β [SE], 0.11 [0.02]; P = 2.6 × 10-12). The mediating role of EA differed between national contexts. Higher cognitive performance PGS were associated with reduced odds of AUD in Yale-Penn participants (OR, 0.83; 95% CI, 0.78-0.89).Conclusions and RelevanceIQ and cognitive performance have a significant but context-dependent association with AUD risk, highlighting the need for a better understanding of the interplay among genetic factors, cognitive traits, and sociocultural influences on AUD susceptibility.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"3 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194533","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 : 2025-10-01DOI: 10.1001/jamapsychiatry.2025.2525
Iris E Sommer,Franciska de Beer,Shiral Gangadin,Lieuwe de Haan,Wim Veling,Nico van Beveren,Nynke Boonstra,Bram-Sieben Rosema,Jim van Os,Martijn Kikkert,Sanne Koops,Jort Noorman,Frederick Thielen,Ben Wijnen,Marieke Begemann,
ImportanceDose reduction or discontinuation (DRD) early after remission from first-episode psychosis (FEP) increases short-term relapse risk. Controversy remains regarding potential benefits in functioning over the longer term because studies with long-term outcomes show conflicting findings.ObjectiveTo compare short- and long-term effects between DRD and maintenance medication over a 4-year period in a large sample of patients with FEP.Design, Setting, and ParticipantsThe Handling Antipsychotic Medication Long-Term Evaluation of Targeted Treatment (HAMLETT) study is a single-blind pragmatic randomized (1:1) clinical trial conducted in 26 specialized psychosis units in the Netherlands from September 2017 to March 2023. Patients remitted for FEP from in- and outpatient services were included.InterventionsDRD within 12 months after remission compared with 12 months maintenance treatment.Main Outcomes and MeasuresThe primary outcome was patient-rated functioning, measured by the World Health Organization Disability Assessment Schedule 2.0 (WHODAS-2). Secondary outcomes were researcher-rated global assessment of functioning (GAF), quality of life, relapse, symptom severity (measured by the Positive and Negative Syndrome Scale [PANSS]), serious adverse events, and adverse effects.ResultsA total of 347 patients (241 male [69.5%]; mean [SD] age, 27.9 [8.7] years) were included, with 168 randomized to early DRD and 179 to maintenance. WHODAS-2 showed no time × condition interaction. In the first year, DRD was associated with higher risk of relapse (odds ratio, 2.84; 95% CI, 1.08 to 7.66; P = .04) and lower quality of life (β = -3.31; 95% CI, -6.34 to -0.29; P = .03). At 3 years (β = 3.61; 95% CI, 0.28 to 6.95; P = .03) and 4 years (β = 6.13; 95% CI, 2.03 to 10.22; P = .003), a nonlinear effect of time occurred, showing significantly better GAF for patients in the DRD condition, with a similar trend for PANSS at 4 years (P for trend = .06). Although SAEs and adverse effects were similar between groups, 3 confirmed deaths by suicide occurred in the DRD group, against 1 death by suicide in the maintenance group.Conclusions and RelevanceThis randomized clinical trial found that DRD posed risks of relapse and worse quality of life over the first year but yielded better researcher-rated functioning at the third and fourth year, with a similar trend for symptom severity; because antipsychotic medication doses were comparable in the 2 groups from 1 year onwards, this finding is not a direct result of lower medication but may reflect a learning experience to use antipsychotics to better handle psychotic vulnerability. These findings suggest that the potential learning and empowering element of DRD needs to be weighed carefully against short-term risks.Trial registrationEudraCT number: 2017-002406-12.
{"title":"Early Dose Reduction or Discontinuation vs Maintenance Antipsychotics After First Psychotic Episode Remission: A Randomized Clinical Trial.","authors":"Iris E Sommer,Franciska de Beer,Shiral Gangadin,Lieuwe de Haan,Wim Veling,Nico van Beveren,Nynke Boonstra,Bram-Sieben Rosema,Jim van Os,Martijn Kikkert,Sanne Koops,Jort Noorman,Frederick Thielen,Ben Wijnen,Marieke Begemann, ","doi":"10.1001/jamapsychiatry.2025.2525","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.2525","url":null,"abstract":"ImportanceDose reduction or discontinuation (DRD) early after remission from first-episode psychosis (FEP) increases short-term relapse risk. Controversy remains regarding potential benefits in functioning over the longer term because studies with long-term outcomes show conflicting findings.ObjectiveTo compare short- and long-term effects between DRD and maintenance medication over a 4-year period in a large sample of patients with FEP.Design, Setting, and ParticipantsThe Handling Antipsychotic Medication Long-Term Evaluation of Targeted Treatment (HAMLETT) study is a single-blind pragmatic randomized (1:1) clinical trial conducted in 26 specialized psychosis units in the Netherlands from September 2017 to March 2023. Patients remitted for FEP from in- and outpatient services were included.InterventionsDRD within 12 months after remission compared with 12 months maintenance treatment.Main Outcomes and MeasuresThe primary outcome was patient-rated functioning, measured by the World Health Organization Disability Assessment Schedule 2.0 (WHODAS-2). Secondary outcomes were researcher-rated global assessment of functioning (GAF), quality of life, relapse, symptom severity (measured by the Positive and Negative Syndrome Scale [PANSS]), serious adverse events, and adverse effects.ResultsA total of 347 patients (241 male [69.5%]; mean [SD] age, 27.9 [8.7] years) were included, with 168 randomized to early DRD and 179 to maintenance. WHODAS-2 showed no time × condition interaction. In the first year, DRD was associated with higher risk of relapse (odds ratio, 2.84; 95% CI, 1.08 to 7.66; P = .04) and lower quality of life (β = -3.31; 95% CI, -6.34 to -0.29; P = .03). At 3 years (β = 3.61; 95% CI, 0.28 to 6.95; P = .03) and 4 years (β = 6.13; 95% CI, 2.03 to 10.22; P = .003), a nonlinear effect of time occurred, showing significantly better GAF for patients in the DRD condition, with a similar trend for PANSS at 4 years (P for trend = .06). Although SAEs and adverse effects were similar between groups, 3 confirmed deaths by suicide occurred in the DRD group, against 1 death by suicide in the maintenance group.Conclusions and RelevanceThis randomized clinical trial found that DRD posed risks of relapse and worse quality of life over the first year but yielded better researcher-rated functioning at the third and fourth year, with a similar trend for symptom severity; because antipsychotic medication doses were comparable in the 2 groups from 1 year onwards, this finding is not a direct result of lower medication but may reflect a learning experience to use antipsychotics to better handle psychotic vulnerability. These findings suggest that the potential learning and empowering element of DRD needs to be weighed carefully against short-term risks.Trial registrationEudraCT number: 2017-002406-12.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"7 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194535","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 : 2025-10-01DOI: 10.1001/jamapsychiatry.2025.2700
David Eddie,Marina Nguyen,Katherine Zeng,Sara Mei,Noah Emery
ImportancePreliminary studies suggest heart rate variability biofeedback (HRVB) may reduce craving and negative affect in individuals with substance use disorder (SUD), but few studies have evaluated whether this translates into improved substance use outcomes, and no prior studies have examined second-generation wearable HRVB technology in this context.ObjectiveTo evaluate the effects of second-generation HRVB on negative affect, positive affect, craving, and alcohol and other drug (AOD) use in adults with SUD.Design, Setting, and ParticipantsThis phase 2 randomized clinical trial included 8 weeks of outpatient treatment. Recruitment was conducted virtually across the US from February 2023 to June 2024. Treatment-seeking adults with SUD were randomized to receive HRVB + treatment as usual (TAU) or TAU only.InterventionEight weeks of HRVB.Main Outcomes and MeasuresThe primary outcomes were negative affect, positive affect, craving, and substance use, assessed with ecological momentary assessment.ResultsOf 260 individuals assessed for eligibility, 120 were randomized to receive HRVB + TAU or TAU only. Among study participants (69 female participants of 115 [60.0%]; mean [SD] age, 46.18 [11.59] years), HRVB was associated with significant reductions in negative affect (b, -0.01; z, -3.21; P = .001) and craving (b, -0.01; z, -4.60; P < .001) over 8 weeks. In contrast, the control group experienced increases in both negative affect and craving. No differences were observed for positive affect. HRVB was also associated with a significantly lower proportion of AOD use days (odds ratio [OR], 0.36; 95% credible interval [CrI], 0.25-0.54), representing a 64% reduction in AOD use compared to controls. Treatment condition moderated the within-person relationship between craving and later AOD use (OR, 0.84; 95% CrI, 0.73-0.97), such that those receiving HRVB were less likely to use AOD following craving (b, -0.18; 95% CrI, -0.32 to -0.03).Conclusions and RelevanceIn this randomized clinical trial, findings suggest second-generation HRVB can reduce negative affect, craving, and substance use among individuals in early recovery from SUD. HRVB appears to confer benefit in part by disrupting the association between craving and subsequent AOD use; these results support HRVB as a potentially efficacious treatment for SUD and warrant further investigation in phase 3 trials.Trial RegistrationClinicalTrials.gov Identifier: NCT05454657.
{"title":"Heart Rate Variability Biofeedback for Substance Use Disorder: A Randomized Clinical Trial.","authors":"David Eddie,Marina Nguyen,Katherine Zeng,Sara Mei,Noah Emery","doi":"10.1001/jamapsychiatry.2025.2700","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.2700","url":null,"abstract":"ImportancePreliminary studies suggest heart rate variability biofeedback (HRVB) may reduce craving and negative affect in individuals with substance use disorder (SUD), but few studies have evaluated whether this translates into improved substance use outcomes, and no prior studies have examined second-generation wearable HRVB technology in this context.ObjectiveTo evaluate the effects of second-generation HRVB on negative affect, positive affect, craving, and alcohol and other drug (AOD) use in adults with SUD.Design, Setting, and ParticipantsThis phase 2 randomized clinical trial included 8 weeks of outpatient treatment. Recruitment was conducted virtually across the US from February 2023 to June 2024. Treatment-seeking adults with SUD were randomized to receive HRVB + treatment as usual (TAU) or TAU only.InterventionEight weeks of HRVB.Main Outcomes and MeasuresThe primary outcomes were negative affect, positive affect, craving, and substance use, assessed with ecological momentary assessment.ResultsOf 260 individuals assessed for eligibility, 120 were randomized to receive HRVB + TAU or TAU only. Among study participants (69 female participants of 115 [60.0%]; mean [SD] age, 46.18 [11.59] years), HRVB was associated with significant reductions in negative affect (b, -0.01; z, -3.21; P = .001) and craving (b, -0.01; z, -4.60; P < .001) over 8 weeks. In contrast, the control group experienced increases in both negative affect and craving. No differences were observed for positive affect. HRVB was also associated with a significantly lower proportion of AOD use days (odds ratio [OR], 0.36; 95% credible interval [CrI], 0.25-0.54), representing a 64% reduction in AOD use compared to controls. Treatment condition moderated the within-person relationship between craving and later AOD use (OR, 0.84; 95% CrI, 0.73-0.97), such that those receiving HRVB were less likely to use AOD following craving (b, -0.18; 95% CrI, -0.32 to -0.03).Conclusions and RelevanceIn this randomized clinical trial, findings suggest second-generation HRVB can reduce negative affect, craving, and substance use among individuals in early recovery from SUD. HRVB appears to confer benefit in part by disrupting the association between craving and subsequent AOD use; these results support HRVB as a potentially efficacious treatment for SUD and warrant further investigation in phase 3 trials.Trial RegistrationClinicalTrials.gov Identifier: NCT05454657.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"69 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194534","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}
ImportanceTransdiagnostic clinical staging models for mental disorders are receiving increased attention. However, their underlying assumptions are underresearched; for example, it is not clear whether the observed progression across stages occurs independently of preexisting risk factors.ObjectivesTo test the likelihood of progression from stage 0 (familial risk) in childhood to stage 1a (mild symptoms) in adolescence and subsequently to stage 1b (clinically significant symptoms) in young adulthood, accounting for confounders, and to explore potential mediators.Design, Setting, and ParticipantsThis prospective cohort study included participants from the Avon Longitudinal Study of Parents and Children (ALSPAC). ALSPAC included pregnant women and their offspring residing in Avon, United Kingdom, between 1991 and 1992, with a proportion of offspring followed up into young adulthood. Eligible participants provided data on stage determinants and potential confounders from birth until age 24 years. Data were collected from 1991 to 2015 and analyzed from January 2002 to June 2025.ExposuresExposures were clinical stages 0 and 1a in separate tests of association with stages 1a and 1b, respectively. Criteria for stage 0 were the presence of schizophrenia or severe depression in a first-degree relative. Criteria for stage 1a were the presence of 1 to 2 symptoms of depression, anxiety, or psychosis at ages 12 to 13 years.Main Outcomes and MeasuresOutcomes were stage 1a in adolescence and stage 1b in young adulthood. Criteria for stage 1b were at least moderate symptoms of depression, anxiety, or psychosis, with associated functional impact at ages 18 to 24 years. Confounders were sex assigned at birth, obstetric risk, parental social class, ethnicity, family adversity, temperament, early life events, and neurocognition, measured in childhood.ResultsAmong those with complete data at all 3 time points (1375 participants; weighted, 7342), 796 participants (57.9%; weighted, 51.5%) were female and 579 (42.1%; weighted, 48.5%) were male. After adjusting for potential confounders, there was an association between stage 0 in childhood and stage 1a in adolescence (3860 participants; weighted, 7388 participants; odds ratio [OR], 1.65, 95% CI, 1.30-2.11) and between stage 1a in adolescence and stage 1b in young adulthood (1661 participants; weighted, 7466 participants; OR, 2.07; 95% CI, 1.07-4.01). Level of neuroticism in adolescence mediated 18% of the association between stage 1a in adolescence and stage 1b in young adulthood.Conclusions and RelevanceIn this cohort study, young people with mental health problems meeting criteria for early clinical stages were at heightened risk of developing subsequent stages, independent of early life risk factors. This study supports the assumption of progression underlying clinical staging models for mental disorders.
{"title":"Progression of Transdiagnostic Stages From Childhood to Young Adulthood.","authors":"Aswin Ratheesh,Yufan Chen,Dylan Hammond,Zoe Aitken,Jai Shah,Frank Iorfino,Jan Scott,Ian Hickie,Chris Davey,Andrew Chanen,Michael Berk,Patrick McGorry,Steven Marwaha,Andrew Thompson,Barnaby Nelson","doi":"10.1001/jamapsychiatry.2025.2648","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.2648","url":null,"abstract":"ImportanceTransdiagnostic clinical staging models for mental disorders are receiving increased attention. However, their underlying assumptions are underresearched; for example, it is not clear whether the observed progression across stages occurs independently of preexisting risk factors.ObjectivesTo test the likelihood of progression from stage 0 (familial risk) in childhood to stage 1a (mild symptoms) in adolescence and subsequently to stage 1b (clinically significant symptoms) in young adulthood, accounting for confounders, and to explore potential mediators.Design, Setting, and ParticipantsThis prospective cohort study included participants from the Avon Longitudinal Study of Parents and Children (ALSPAC). ALSPAC included pregnant women and their offspring residing in Avon, United Kingdom, between 1991 and 1992, with a proportion of offspring followed up into young adulthood. Eligible participants provided data on stage determinants and potential confounders from birth until age 24 years. Data were collected from 1991 to 2015 and analyzed from January 2002 to June 2025.ExposuresExposures were clinical stages 0 and 1a in separate tests of association with stages 1a and 1b, respectively. Criteria for stage 0 were the presence of schizophrenia or severe depression in a first-degree relative. Criteria for stage 1a were the presence of 1 to 2 symptoms of depression, anxiety, or psychosis at ages 12 to 13 years.Main Outcomes and MeasuresOutcomes were stage 1a in adolescence and stage 1b in young adulthood. Criteria for stage 1b were at least moderate symptoms of depression, anxiety, or psychosis, with associated functional impact at ages 18 to 24 years. Confounders were sex assigned at birth, obstetric risk, parental social class, ethnicity, family adversity, temperament, early life events, and neurocognition, measured in childhood.ResultsAmong those with complete data at all 3 time points (1375 participants; weighted, 7342), 796 participants (57.9%; weighted, 51.5%) were female and 579 (42.1%; weighted, 48.5%) were male. After adjusting for potential confounders, there was an association between stage 0 in childhood and stage 1a in adolescence (3860 participants; weighted, 7388 participants; odds ratio [OR], 1.65, 95% CI, 1.30-2.11) and between stage 1a in adolescence and stage 1b in young adulthood (1661 participants; weighted, 7466 participants; OR, 2.07; 95% CI, 1.07-4.01). Level of neuroticism in adolescence mediated 18% of the association between stage 1a in adolescence and stage 1b in young adulthood.Conclusions and RelevanceIn this cohort study, young people with mental health problems meeting criteria for early clinical stages were at heightened risk of developing subsequent stages, independent of early life risk factors. This study supports the assumption of progression underlying clinical staging models for mental disorders.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"12 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127093","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 : 2025-09-24DOI: 10.1001/jamapsychiatry.2025.2572
Hui Wang,Krisztina D László
ImportanceParental mental disorders are associated with increased risks of infant mortality and with several developmental, mental, and somatic health outcomes, yet their associations with long-term morality in offspring remain unknown.ObjectiveTo investigate the associations between parental mental disorders and the risk of mortality in offspring up to middle age.Design, Setting, and ParticipantsThis nationwide register-based cohort study used data for individuals born in Sweden from January 1973 to December 2014. Data were analyzed from October 2024 to March 2025.ExposureParental mental disorders identified from the Patient Register.Main Outcomes and MeasuresThe outcomes were offspring mortality, including deaths due to any, natural, and unnatural causes, from birth up to December 31, 2023. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% CIs for offspring mortality according to parental mental disorders. Cousin comparison analysis was performed to assess familial confounding due to genetic and shared environmental factors.ResultsAmong 3 548 788 offspring, 1 818 232 were male (51.2%; 635 213 exposed to parental mental disorders) and 1 730 556 were female (48.8%; 605 935 exposed to parental mental disorders). The mean (SD) age at index parental diagnosis was 15.8 (13.3) years. During a median (IQR) follow-up of 20.1 (11.5-32.5) years (age range at end of follow-up, 9-51 years), there were 12 725 deaths (7.93 per 10 000 person-years) among offspring exposed to parental mental disorders and 30 087 deaths (3.55 per 10 000 person-years) among unexposed offspring. Offspring exposed to parental mental disorders had increased risks of all-cause mortality (HR, 2.13; 95% CI, 2.08-2.18) and death due to natural (HR, 1.88; 95% CI, 1.83-1.95) and unnatural causes (HR, 2.45; 95% CI, 2.37-2.54). All major types of parental mental disorders were associated with increased risks of offspring mortality, with the HRs ranging from 1.58 (95% CI, 1.40-1.79) for eating disorders to 2.22 (95% CI, 1.89-2.62) for intellectual disability. The associations were strongest if both parents were diagnosed with mental disorders and did not differ significantly according to the affected parents' sex and the child's age at parental diagnosis. The observed associations remained similar in the cousin comparison analyses.Conclusions and RelevanceOffspring of parents with mental disorders had an increased risk of mortality up to the age of 51 years. The associations were observed for all major types of parental mental disorders and were strongest in case of unnatural deaths, especially when both parents were diagnosed with mental disorders. These findings emphasize the importance of providing support for families with parents with mental disorders; further studies are needed to investigate whether such support may reduce the risk of premature death in affected offspring.
{"title":"Parental Mental Disorders and Offspring Mortality up to Middle Age.","authors":"Hui Wang,Krisztina D László","doi":"10.1001/jamapsychiatry.2025.2572","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.2572","url":null,"abstract":"ImportanceParental mental disorders are associated with increased risks of infant mortality and with several developmental, mental, and somatic health outcomes, yet their associations with long-term morality in offspring remain unknown.ObjectiveTo investigate the associations between parental mental disorders and the risk of mortality in offspring up to middle age.Design, Setting, and ParticipantsThis nationwide register-based cohort study used data for individuals born in Sweden from January 1973 to December 2014. Data were analyzed from October 2024 to March 2025.ExposureParental mental disorders identified from the Patient Register.Main Outcomes and MeasuresThe outcomes were offspring mortality, including deaths due to any, natural, and unnatural causes, from birth up to December 31, 2023. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% CIs for offspring mortality according to parental mental disorders. Cousin comparison analysis was performed to assess familial confounding due to genetic and shared environmental factors.ResultsAmong 3 548 788 offspring, 1 818 232 were male (51.2%; 635 213 exposed to parental mental disorders) and 1 730 556 were female (48.8%; 605 935 exposed to parental mental disorders). The mean (SD) age at index parental diagnosis was 15.8 (13.3) years. During a median (IQR) follow-up of 20.1 (11.5-32.5) years (age range at end of follow-up, 9-51 years), there were 12 725 deaths (7.93 per 10 000 person-years) among offspring exposed to parental mental disorders and 30 087 deaths (3.55 per 10 000 person-years) among unexposed offspring. Offspring exposed to parental mental disorders had increased risks of all-cause mortality (HR, 2.13; 95% CI, 2.08-2.18) and death due to natural (HR, 1.88; 95% CI, 1.83-1.95) and unnatural causes (HR, 2.45; 95% CI, 2.37-2.54). All major types of parental mental disorders were associated with increased risks of offspring mortality, with the HRs ranging from 1.58 (95% CI, 1.40-1.79) for eating disorders to 2.22 (95% CI, 1.89-2.62) for intellectual disability. The associations were strongest if both parents were diagnosed with mental disorders and did not differ significantly according to the affected parents' sex and the child's age at parental diagnosis. The observed associations remained similar in the cousin comparison analyses.Conclusions and RelevanceOffspring of parents with mental disorders had an increased risk of mortality up to the age of 51 years. The associations were observed for all major types of parental mental disorders and were strongest in case of unnatural deaths, especially when both parents were diagnosed with mental disorders. These findings emphasize the importance of providing support for families with parents with mental disorders; further studies are needed to investigate whether such support may reduce the risk of premature death in affected offspring.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"16 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127055","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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