Pub Date : 2025-11-12DOI: 10.1001/jamapsychiatry.2025.3151
Kristen L Eckstrand,Emrys Fiona Fonseca,Kellan Baker,Katie Dalke
{"title":"Mental Health and Care Denial in Transgender Youth.","authors":"Kristen L Eckstrand,Emrys Fiona Fonseca,Kellan Baker,Katie Dalke","doi":"10.1001/jamapsychiatry.2025.3151","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.3151","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"137 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145491505","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 : 2025-11-06DOI: 10.1001/jamapsychiatry.2025.3271
Caspar J. Geissler, Tsen Vei Lim, Herbert A. Görne, Sylke Krenkel, Christian Büchel, Karen D. Ersche
Importance The opioid crisis remains a global public health issue, with poor clinical outcomes, low treatment adherence, and early dropouts being major challenges. These may be driven by a pathological increase in avoidance tendencies in opioid addiction, although this has not yet been demonstrated in humans. Objective To determine whether opioid addiction is characterized by increased avoidance learning and whether this is also observed in individuals with chronic nonaddicted opioid use. Design, Setting, and Participants This case-control study conducted in Hamburg, Germany, used a probabilistic reinforcement learning task to investigate how individuals with chronic opioid use (both with and without opioid addiction) learn from negative outcomes. Participants were recruited from outpatient clinics for either addiction or chronic pain between December 2021 and October 2024. Data analysis was conducted between January 2025 and February 2025. Computational modeling was applied to assess whether participants learned more effectively from experiencing or avoiding financial loss and to ascertain their response tendencies. Main Outcomes and Measures The primary outcomes were computational parameters of learning from experiencing financial loss, learning from avoiding it (ie, negative reinforcement), choice consistency, and a response tendency to repeat. General and drug-related compulsivity, automatic habits, and avoidance tendencies were assessed by self-report. Results This study’s sample included 88 participants (47 female participants [53%]; mean [SD] age, 44 [10.9] years). Both participants with opioid addiction and those using opioids chronically showed increased learning from negative reinforcement ( F2,83 = 15.8; P < .001; mean difference [MD] = 0.071; 95% CI, 0.02-0.12) and reduced choice consistency ( F2,83 = 10.4; P < .001; MD = −1.31; 95% CI, −2.03 to −0.59). Variations in avoidance learning predicted both their self-reported avoidance behavior in daily life and the severity of compulsive opioid use. The 2 opioid user groups did not differ in terms of learning from monetary loss ( F2,83 = 2.91; P = .06) or their tendency to repeat prior responses ( F2,83 = 1.84; P = .17). Conclusions and Relevance This cross-sectional study supports preclinical findings emphasizing the role of negative reinforcement in opioid addiction, although this has not been shown in humans before. The results indicate that negative reinforcement is relevant even in the early stages of opioid use, suggesting potential new avenues for prevention an
阿片类药物危机仍然是一个全球性的公共卫生问题，临床结果不佳、治疗依从性低和早期辍学是主要挑战。这些可能是由阿片类药物成瘾中回避倾向的病理增加所驱动的，尽管这尚未在人类中得到证实。目的确定阿片类药物成瘾是否以回避学习增加为特征，以及慢性非阿片类药物成瘾者是否也存在这种特征。本病例对照研究在德国汉堡进行，使用概率强化学习任务来调查慢性阿片类药物使用个体（包括阿片类药物成瘾和非阿片类药物成瘾）如何从负面结果中学习。参与者在2021年12月至2024年10月期间从门诊诊所招募成瘾或慢性疼痛患者。数据分析在2025年1月至2025年2月之间进行。计算模型应用于评估参与者是否从经历或避免经济损失中更有效地学习，并确定他们的反应倾向。主要结果和测量方法主要结果为从经历经济损失中学习、从避免经济损失中学习（即负强化）、选择一致性和重复反应倾向的计算参数。一般和药物相关的强迫，自动习惯和回避倾向评估自我报告。本研究共纳入88例受试者，其中女性47例（53%），平均[SD]年龄44[10.9]岁。阿片类药物成瘾的参与者和长期使用阿片类药物的参与者都表现出从负强化中学习的增加（f2,83 = 15.8; P & lt; .001；平均差异[MD] = 0.071; 95% CI, 0.02-0.12）和选择一致性的降低（f2,83 = 10.4; P & lt; .001; MD = - 1.31; 95% CI, - 2.03至- 0.59）。回避学习的差异预测了他们在日常生活中自我报告的回避行为和强迫性阿片类药物使用的严重程度。两个阿片类药物使用者群体在从金钱损失中学习方面没有差异（f2,83 = 2.91; P = 0.06）或他们重复先前反应的倾向（f2,83 = 1.84; P = 0.17）。这项横断面研究支持临床前研究结果，强调负强化在阿片类药物成瘾中的作用，尽管这之前尚未在人类中得到证实。结果表明，即使在阿片类药物使用的早期阶段，负强化也是相关的，这为预防和治疗提供了潜在的新途径。
{"title":"Increased Avoidance Learning in Chronic Opioid Users","authors":"Caspar J. Geissler, Tsen Vei Lim, Herbert A. Görne, Sylke Krenkel, Christian Büchel, Karen D. Ersche","doi":"10.1001/jamapsychiatry.2025.3271","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.3271","url":null,"abstract":"Importance The opioid crisis remains a global public health issue, with poor clinical outcomes, low treatment adherence, and early dropouts being major challenges. These may be driven by a pathological increase in avoidance tendencies in opioid addiction, although this has not yet been demonstrated in humans. Objective To determine whether opioid addiction is characterized by increased avoidance learning and whether this is also observed in individuals with chronic nonaddicted opioid use. Design, Setting, and Participants This case-control study conducted in Hamburg, Germany, used a probabilistic reinforcement learning task to investigate how individuals with chronic opioid use (both with and without opioid addiction) learn from negative outcomes. Participants were recruited from outpatient clinics for either addiction or chronic pain between December 2021 and October 2024. Data analysis was conducted between January 2025 and February 2025. Computational modeling was applied to assess whether participants learned more effectively from experiencing or avoiding financial loss and to ascertain their response tendencies. Main Outcomes and Measures The primary outcomes were computational parameters of learning from experiencing financial loss, learning from avoiding it (ie, negative reinforcement), choice consistency, and a response tendency to repeat. General and drug-related compulsivity, automatic habits, and avoidance tendencies were assessed by self-report. Results This study’s sample included 88 participants (47 female participants [53%]; mean [SD] age, 44 [10.9] years). Both participants with opioid addiction and those using opioids chronically showed increased learning from negative reinforcement ( <jats:italic toggle=\"yes\">F</jats:italic> <jats:sub>2,83</jats:sub> = 15.8; <jats:italic toggle=\"yes\">P</jats:italic> &amp;lt; .001; mean difference [MD] = 0.071; 95% CI, 0.02-0.12) and reduced choice consistency ( <jats:italic toggle=\"yes\">F</jats:italic> <jats:sub>2,83</jats:sub> = 10.4; <jats:italic toggle=\"yes\">P</jats:italic> &amp;lt; .001; MD = −1.31; 95% CI, −2.03 to −0.59). Variations in avoidance learning predicted both their self-reported avoidance behavior in daily life and the severity of compulsive opioid use. The 2 opioid user groups did not differ in terms of learning from monetary loss ( <jats:italic toggle=\"yes\">F</jats:italic> <jats:sub>2,83</jats:sub> = 2.91; <jats:italic toggle=\"yes\">P</jats:italic> = .06) or their tendency to repeat prior responses ( <jats:italic toggle=\"yes\">F</jats:italic> <jats:sub>2,83</jats:sub> = 1.84; <jats:italic toggle=\"yes\">P</jats:italic> = .17). Conclusions and Relevance This cross-sectional study supports preclinical findings emphasizing the role of negative reinforcement in opioid addiction, although this has not been shown in humans before. The results indicate that negative reinforcement is relevant even in the early stages of opioid use, suggesting potential new avenues for prevention an","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"132 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145447175","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}
ImportanceThis study provides insight into change patterns of posttraumatic stress disorder (PTSD), complex PTSD (CPTSD), and prolonged grief disorder (PGD) under conditions of continuous trauma. Clarification of how these disorders are associated with somatization and pain is essential for the assessment and development of integrated care models for continuous trauma-exposed populations.ObjectiveTo examine longitudinal change patterns of PTSD, CPTSD, and PGD and assess their associations with somatization and pain.Design, Setting, and ParticipantsA population-based cohort study was conducted between November 2023 and December 2024 using an online panel survey in a nationally representative sample of Israeli adults (aged 18-71 years) exposed to the October 7, 2023, terror attack and subsequent war. Quota sampling was used to match the national census on age and sex. Eligibility criteria included age 18 years or older, Hebrew fluency, residency in Israel during data collection, and provision of written informed consent. Change patterns were identified across 2 measurements, approximately 1 year apart.Main Outcomes and MeasuresProbable PTSD and CPTSD were assessed using the International Trauma Questionnaire and PGD via the International Grief Questionnaire, based on standard cutoffs. Somatization was measured using the Somatic Symptom Scale-8 and pain using the Short-Form McGill Pain Questionnaire.ResultsOf the 2028 participants at baseline (mean [SD] age, 42.7 [14.6] years; 51.4% women), 1598 (78.8%) completed the follow-up assessment 1 year later (mean [SD] age, 42.7 [14.6] years; 51.4% women). PTSD decreased from 17.8% to 8.2% and CPTSD from 13.1% to 9.3%; PGD remained stable (4.4% to 4.3%). The resilient pattern was most common (PTSD and CPTSD, 62.7%; PGD, 93.0%). Chronic, delayed, and shifting patterns (PTSD and CPTSD, 3.0%-4.5%; PGD, 1.7%-2.6%) were significantly associated with greater somatization (PTSD and CPTSD, η2 = 0.205; 95% CI, 0.200-0.215; P < .001; PGD, η2 = 0.036; 95% CI, 0.029-0.042; P < .001), sensory pain (PTSD and CPTSD, η2 = 0.087; 95% CI, 0.075-0.099; P < .001; PGD, η2 = 0.029; 95% CI, 0.015-0.043; P < .001), and affective pain (PTSD and CPTSD, η2 = 0.088; 95% CI, 0.071-0.105; P < .001; PGD, η2 = 0.033; 95% CI, 0.017-0.049; P < .001), with large effect sizes for PTSD and CPTSD somatization and small to medium effect sizes for all other associations.Conclusions and RelevanceThis cohort study provides a longitudinal view of stress-related disorders during ongoing trauma, showing dynamic PTSD and CPTSD patterns and stable PGD. The association between psychological distress and somatic burden emphasizes the need for trauma-informed care addressing mental and physical health under long-term exposure.
{"title":"Change Patterns of Posttraumatic and Grief Disorders and Their Somatic Variables in Ongoing Trauma.","authors":"Yafit Levin,Menachem Ben-Ezra,Elazar Leshem,Yaira Hamama-Raz","doi":"10.1001/jamapsychiatry.2025.3046","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.3046","url":null,"abstract":"ImportanceThis study provides insight into change patterns of posttraumatic stress disorder (PTSD), complex PTSD (CPTSD), and prolonged grief disorder (PGD) under conditions of continuous trauma. Clarification of how these disorders are associated with somatization and pain is essential for the assessment and development of integrated care models for continuous trauma-exposed populations.ObjectiveTo examine longitudinal change patterns of PTSD, CPTSD, and PGD and assess their associations with somatization and pain.Design, Setting, and ParticipantsA population-based cohort study was conducted between November 2023 and December 2024 using an online panel survey in a nationally representative sample of Israeli adults (aged 18-71 years) exposed to the October 7, 2023, terror attack and subsequent war. Quota sampling was used to match the national census on age and sex. Eligibility criteria included age 18 years or older, Hebrew fluency, residency in Israel during data collection, and provision of written informed consent. Change patterns were identified across 2 measurements, approximately 1 year apart.Main Outcomes and MeasuresProbable PTSD and CPTSD were assessed using the International Trauma Questionnaire and PGD via the International Grief Questionnaire, based on standard cutoffs. Somatization was measured using the Somatic Symptom Scale-8 and pain using the Short-Form McGill Pain Questionnaire.ResultsOf the 2028 participants at baseline (mean [SD] age, 42.7 [14.6] years; 51.4% women), 1598 (78.8%) completed the follow-up assessment 1 year later (mean [SD] age, 42.7 [14.6] years; 51.4% women). PTSD decreased from 17.8% to 8.2% and CPTSD from 13.1% to 9.3%; PGD remained stable (4.4% to 4.3%). The resilient pattern was most common (PTSD and CPTSD, 62.7%; PGD, 93.0%). Chronic, delayed, and shifting patterns (PTSD and CPTSD, 3.0%-4.5%; PGD, 1.7%-2.6%) were significantly associated with greater somatization (PTSD and CPTSD, η2 = 0.205; 95% CI, 0.200-0.215; P < .001; PGD, η2 = 0.036; 95% CI, 0.029-0.042; P < .001), sensory pain (PTSD and CPTSD, η2 = 0.087; 95% CI, 0.075-0.099; P < .001; PGD, η2 = 0.029; 95% CI, 0.015-0.043; P < .001), and affective pain (PTSD and CPTSD, η2 = 0.088; 95% CI, 0.071-0.105; P < .001; PGD, η2 = 0.033; 95% CI, 0.017-0.049; P < .001), with large effect sizes for PTSD and CPTSD somatization and small to medium effect sizes for all other associations.Conclusions and RelevanceThis cohort study provides a longitudinal view of stress-related disorders during ongoing trauma, showing dynamic PTSD and CPTSD patterns and stable PGD. The association between psychological distress and somatic burden emphasizes the need for trauma-informed care addressing mental and physical health under long-term exposure.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"112 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145440768","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 : 2025-11-05DOI: 10.1001/jamapsychiatry.2025.3261
Reinhard Janssen-Aguilar,Tulassi Vije,Malika Peera,Huda F Al-Shamali,Shakila Meshkat,Qiaowei Lin,Wendy Lou,Hugo Laviada-Molina,Mary L Phillips,Venkat Bhat
ImportanceKetogenic diets (KDs) have been hypothesized to influence mental health through pathways involving mitochondrial function, inflammation, and neurotransmitters, but their therapeutic value in psychiatric populations remains uncertain.ObjectiveTo assess the associations between KDs and mental health outcomes in adults, with a focus on depressive and anxiety symptoms.Data SourcesMEDLINE, Embase, and APA PsycINFO were searched on April 18, 2025. Additional studies were identified through manual searches and clinical trial registries.Study SelectionStudies involving adults aged 18 years or older receiving a KD (<26% energy from carbohydrates or <50 g/day) and assessed with validated psychiatric scales were eligible. Designs included randomized clinical trials (RCTs), quasi-experimental (QSE) studies, cross-sectional studies, case series, and case reports.Data Extraction and SynthesisData were extracted by 1 reviewer and verified by 2 others. Risk of bias was assessed using critical appraisal tools from the Joanna Briggs Institute. Random-effects meta-analyses were run separately for RCTs and QSEs.Main Outcomes and MeasuresThe primary outcome was changes in psychiatric symptom severity measured by standardized scales, reported as standardized mean differences (SMDs) or standardized mean change using change scores (SMCCs).ResultsA total of 50 studies (41 718 participants) were included. Ten RCTs on KD for depressive symptoms vs control diets showed a significant association (SMD, -0.48; 95% CI, -0.87 to -0.10; I2 = 67.2%), with stronger associations in studies using ketone monitoring, nonobese participants, very low-carbohydrate interventions, and non-high-carbohydrate comparators. Nine RCTs on anxiety showed no significant association (SMD, -0.03; 95% CI, -0.18 to 0.12; I2 = 41%). In QSEs, 9 on depressive symptoms showed a consistent association (SMCC, -0.66; 95% CI, -0.83 to -0.50; I2 = 0%), and 6 on anxiety showed similar results (SMCC, -0.58; 95% CI, -0.81 to -0.36; I2 = 0%).Conclusions and RelevanceIn this systematic review and meta-analysis, KDs were associated with modest improvements in depressive symptoms, particularly with biochemical ketosis verification, while anxiety evidence was inconclusive. Given heterogeneity, comparators, and short follow-up, well-powered trials with standardized, verified protocols, structured support, and prespecified outcomes are needed to confirm efficacy and durability.
{"title":"Ketogenic Diets and Depression and Anxiety: A Systematic Review and Meta-Analysis.","authors":"Reinhard Janssen-Aguilar,Tulassi Vije,Malika Peera,Huda F Al-Shamali,Shakila Meshkat,Qiaowei Lin,Wendy Lou,Hugo Laviada-Molina,Mary L Phillips,Venkat Bhat","doi":"10.1001/jamapsychiatry.2025.3261","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.3261","url":null,"abstract":"ImportanceKetogenic diets (KDs) have been hypothesized to influence mental health through pathways involving mitochondrial function, inflammation, and neurotransmitters, but their therapeutic value in psychiatric populations remains uncertain.ObjectiveTo assess the associations between KDs and mental health outcomes in adults, with a focus on depressive and anxiety symptoms.Data SourcesMEDLINE, Embase, and APA PsycINFO were searched on April 18, 2025. Additional studies were identified through manual searches and clinical trial registries.Study SelectionStudies involving adults aged 18 years or older receiving a KD (<26% energy from carbohydrates or <50 g/day) and assessed with validated psychiatric scales were eligible. Designs included randomized clinical trials (RCTs), quasi-experimental (QSE) studies, cross-sectional studies, case series, and case reports.Data Extraction and SynthesisData were extracted by 1 reviewer and verified by 2 others. Risk of bias was assessed using critical appraisal tools from the Joanna Briggs Institute. Random-effects meta-analyses were run separately for RCTs and QSEs.Main Outcomes and MeasuresThe primary outcome was changes in psychiatric symptom severity measured by standardized scales, reported as standardized mean differences (SMDs) or standardized mean change using change scores (SMCCs).ResultsA total of 50 studies (41 718 participants) were included. Ten RCTs on KD for depressive symptoms vs control diets showed a significant association (SMD, -0.48; 95% CI, -0.87 to -0.10; I2 = 67.2%), with stronger associations in studies using ketone monitoring, nonobese participants, very low-carbohydrate interventions, and non-high-carbohydrate comparators. Nine RCTs on anxiety showed no significant association (SMD, -0.03; 95% CI, -0.18 to 0.12; I2 = 41%). In QSEs, 9 on depressive symptoms showed a consistent association (SMCC, -0.66; 95% CI, -0.83 to -0.50; I2 = 0%), and 6 on anxiety showed similar results (SMCC, -0.58; 95% CI, -0.81 to -0.36; I2 = 0%).Conclusions and RelevanceIn this systematic review and meta-analysis, KDs were associated with modest improvements in depressive symptoms, particularly with biochemical ketosis verification, while anxiety evidence was inconclusive. Given heterogeneity, comparators, and short follow-up, well-powered trials with standardized, verified protocols, structured support, and prespecified outcomes are needed to confirm efficacy and durability.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"3 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145440622","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 : 2025-11-05DOI: 10.1001/jamapsychiatry.2025.3038
Kent E Hutchison,Jake F Hooper,Hollis C Karoly
ImportancePsilocybin use has surged in the US following decriminalization efforts and promising clinical trial results. Mirroring early cannabis legalization, public access and enthusiasm are outpacing regulatory oversight and scientific understanding, posing potential risks to public health.ObjectiveTo review emerging evidence on the public health implications of unregulated psilocybin mushroom use, including trends in use, product variability, co-use with other substances, and age-related differences in outcomes.Evidence ReviewSources included peer-reviewed articles, national surveillance data (eg, poison control center reports), and publicly available chemical testing data from decriminalized jurisdictions. The review emphasizes epidemiological and pharmacological findings published between January 1, 2014, and December 31, 2024, with attention to parallels from cannabis legalization research. Studies were selected based on relevance to nonclinical psilocybin use, product composition, adverse outcomes, and co-use patterns.FindingsPsilocybin mushroom use has sharply increased in the US, particularly among adults aged 19 to 50 years, with more than 7 million individuals reporting use in the past year. This trend has coincided with a substantial increase in poison control center calls related to psychedelics. Testing data from decriminalized regions indicate more than 20-fold variability in psilocybin potency and inconsistent levels of minor tryptamines across mushroom strains. Clinical trial data on synthetic psilocybin do not generalize to public use due to strict participant selection and controlled environments. Co-use with cannabis is common and may increase the risk of adverse events. Evidence also suggests that age may moderate both risks and benefits.Conclusions and RelevanceThe expanding use of unregulated psilocybin mushrooms, combined with high variability in composition and common co-use with other substances, raises urgent public health concerns. Existing clinical data are insufficient to guide harm reduction or policy. There is a pressing need to pivot from controlled efficacy trials to real-world research on psilocybin use, including public education, potency testing, and age-specific risk assessment.
{"title":"Psilocybin Outside the Clinic: Public Health Challenges of Increasing Publicity, Accessibility, and Use.","authors":"Kent E Hutchison,Jake F Hooper,Hollis C Karoly","doi":"10.1001/jamapsychiatry.2025.3038","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.3038","url":null,"abstract":"ImportancePsilocybin use has surged in the US following decriminalization efforts and promising clinical trial results. Mirroring early cannabis legalization, public access and enthusiasm are outpacing regulatory oversight and scientific understanding, posing potential risks to public health.ObjectiveTo review emerging evidence on the public health implications of unregulated psilocybin mushroom use, including trends in use, product variability, co-use with other substances, and age-related differences in outcomes.Evidence ReviewSources included peer-reviewed articles, national surveillance data (eg, poison control center reports), and publicly available chemical testing data from decriminalized jurisdictions. The review emphasizes epidemiological and pharmacological findings published between January 1, 2014, and December 31, 2024, with attention to parallels from cannabis legalization research. Studies were selected based on relevance to nonclinical psilocybin use, product composition, adverse outcomes, and co-use patterns.FindingsPsilocybin mushroom use has sharply increased in the US, particularly among adults aged 19 to 50 years, with more than 7 million individuals reporting use in the past year. This trend has coincided with a substantial increase in poison control center calls related to psychedelics. Testing data from decriminalized regions indicate more than 20-fold variability in psilocybin potency and inconsistent levels of minor tryptamines across mushroom strains. Clinical trial data on synthetic psilocybin do not generalize to public use due to strict participant selection and controlled environments. Co-use with cannabis is common and may increase the risk of adverse events. Evidence also suggests that age may moderate both risks and benefits.Conclusions and RelevanceThe expanding use of unregulated psilocybin mushrooms, combined with high variability in composition and common co-use with other substances, raises urgent public health concerns. Existing clinical data are insufficient to guide harm reduction or policy. There is a pressing need to pivot from controlled efficacy trials to real-world research on psilocybin use, including public education, potency testing, and age-specific risk assessment.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"2010 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145440770","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 : 2025-10-29DOI: 10.1001/jamapsychiatry.2025.3147
Shirley B Wang,Tessa F Blanken,Han L J van der Maas,Denny Borsboom
{"title":"Path Asymmetry in Complex Dynamic Systems of Psychopathology.","authors":"Shirley B Wang,Tessa F Blanken,Han L J van der Maas,Denny Borsboom","doi":"10.1001/jamapsychiatry.2025.3147","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.3147","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"59 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145381133","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 : 2025-10-29DOI: 10.1001/jamapsychiatry.2025.2953
Gregory M Dams,Bethany R Ketchen,Noelle B Smith,Jennifer L Burden
ImportanceThe US Department of Veterans Affairs (VA) reports high demand for mental health residential treatment, which is partially met by private sector care paid for by VA. Little is known about the clinical quality of community programs relative to VA residential treatment.ObjectiveTo assess whether mental health residential care in VA hospitals provides higher-quality care than non-VA programs by examining posttreatment all-cause mortality in matched veterans.Design, Setting, and ParticipantsRetrospective administrative data on 26 464 veterans discharged from their first mental health residential stay between October 1, 2022, and September 30, 2023, were extracted and propensity score matched using an observational/quasi-experimental case-control design to compare VA residential care with VA-paid community residential care.Main Outcomes and MeasuresAll-cause mortality outcomes of matched veterans postdischarge by setting, VA residential treatment compared with VA-paid community residential treatment, using propensity score matching.ResultsThe study sample consisted of matched veterans discharged from VA-paid community residential treatment (n = 7143; median [SD] age, 51.23 [13.29] years; 10.5% female) compared with similar veterans discharged from VA mental health residential treatment (n = 19 321; median [SD] age, 53.57 [12.96] years; 9.1% female) on age, emergency department use, and medical and mental health diagnoses in the year prior to admission. Propensity score-weighted Cox proportional hazards analyses found that, if veterans attending VA-paid community residential treatment had instead discharged from VA residential treatment, they would be estimated to have relatively lower postdischarge mortality rates at 9 months (b = -0.22; robust SE = 0.09; exponentiated value of the slope coefficient [Exp (b)] = 0.81; 95% CI, 0.86-0.95; z = -2.51; P = .01) and 12 months (b = -0.32; robust SE = 0.07; Exp [b] = 0.73; 95% CI, 0.63-0.84; z = -4.29; P < .001).Conclusions and RelevanceCase-control analyses indicate that VA mental health residential treatment demonstrates higher clinical quality compared with VA-paid community residential treatment as evidenced by lower posttreatment all-cause mortality in next year. Additional assessment of cost-benefit tradeoffs is needed.
{"title":"All-Cause Mortality Following Veterans Affairs and Community Mental Health Residential Treatment.","authors":"Gregory M Dams,Bethany R Ketchen,Noelle B Smith,Jennifer L Burden","doi":"10.1001/jamapsychiatry.2025.2953","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.2953","url":null,"abstract":"ImportanceThe US Department of Veterans Affairs (VA) reports high demand for mental health residential treatment, which is partially met by private sector care paid for by VA. Little is known about the clinical quality of community programs relative to VA residential treatment.ObjectiveTo assess whether mental health residential care in VA hospitals provides higher-quality care than non-VA programs by examining posttreatment all-cause mortality in matched veterans.Design, Setting, and ParticipantsRetrospective administrative data on 26 464 veterans discharged from their first mental health residential stay between October 1, 2022, and September 30, 2023, were extracted and propensity score matched using an observational/quasi-experimental case-control design to compare VA residential care with VA-paid community residential care.Main Outcomes and MeasuresAll-cause mortality outcomes of matched veterans postdischarge by setting, VA residential treatment compared with VA-paid community residential treatment, using propensity score matching.ResultsThe study sample consisted of matched veterans discharged from VA-paid community residential treatment (n = 7143; median [SD] age, 51.23 [13.29] years; 10.5% female) compared with similar veterans discharged from VA mental health residential treatment (n = 19 321; median [SD] age, 53.57 [12.96] years; 9.1% female) on age, emergency department use, and medical and mental health diagnoses in the year prior to admission. Propensity score-weighted Cox proportional hazards analyses found that, if veterans attending VA-paid community residential treatment had instead discharged from VA residential treatment, they would be estimated to have relatively lower postdischarge mortality rates at 9 months (b = -0.22; robust SE = 0.09; exponentiated value of the slope coefficient [Exp (b)] = 0.81; 95% CI, 0.86-0.95; z = -2.51; P = .01) and 12 months (b = -0.32; robust SE = 0.07; Exp [b] = 0.73; 95% CI, 0.63-0.84; z = -4.29; P < .001).Conclusions and RelevanceCase-control analyses indicate that VA mental health residential treatment demonstrates higher clinical quality compared with VA-paid community residential treatment as evidenced by lower posttreatment all-cause mortality in next year. Additional assessment of cost-benefit tradeoffs is needed.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"5 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145380974","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 : 2025-10-22DOI: 10.1001/jamapsychiatry.2025.3012
Joyce J Y Lin,Ruby Hickman,Justin Farmer,Michael Leung,Ian W Tang,Kaleigh McAlaine,Tracy Punshon,Brian P Jackson,Felicitas B Bidlack,Scott M Bartell,Joseph J Mangano,Marc G Weisskopf
ImportanceEarly lead exposure is associated with psychological concerns in childhood, but less is known about sensitive periods of exposure or persistence into later adulthood.ObjectiveTo examine the association between prenatal and early postnatal lead exposure and risk of anxiety and depression in later adulthood.Design, Setting, and ParticipantsThis cohort study included participants from the Saint Louis Baby Tooth-Later Life Health Study (SLBT), who donated deciduous (baby) teeth in childhood during the 1950s through 1970s. SLBT participants were recontacted beginning in 2021 to complete health surveys and were masked to lead status. These data were analyzed from February 2025 through May 2025.ExposureLead exposure was measured in baby teeth across prenatal (approximately second trimester to birth, also split into second and approximately third trimesters), and early postnatal (birth to approximately 6 months old) periods.Main Outcomes and MeasuresSelf-reported depressive and anxiety symptoms were assessed via the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder Screener-7 (GAD-7) at a mean age of 62 (SD, 3.6) years. Outcomes were dichotomized using clinical cutoffs for major depressive disorder and generalized anxiety disorder. Secondary analyses treated outcomes as continuous symptom scores.ResultsOf 5131 SLBT participants, 718 (13.3%) had their baby teeth analyzed for lead (381 female [53%] and 334 male [47%]). In total, 695 and 697 participants responded to the PHQ-9 and GAD-7, respectively. The median (25th-75th percentile) combined tooth lead concentration was 1.34 (95% CI, 1.02-1.82) ppm. After adjusting for covariates, an IQR increase in combined tooth lead was associated with nearly 2 times the odds of later adulthood depression (odds ratio, 1.90; 95% CI, 1.20-2.99). The late prenatal period (approximately third trimester) appeared to be the most sensitive window (odds ratio, 1.55; 95% CI, 1.23-1.97). There was no association between early lead exposure and major later adulthood generalized anxiety disorder, but late prenatal and postnatal lead were associated with greater later adulthood anxiety symptoms.Conclusions and RelevanceThird-trimester lead exposure was associated with higher risk of major depressive disorder and anxiety symptoms in later adulthood. These findings emphasize the importance of factoring in later life health outcomes when considering the benefits of lead exposure interventions in childhood and suggest investment in screening and mental health services may be needed to address the long-term burden of historical lead exposure.
{"title":"Prenatal and Early Postnatal Lead Exposure, Sensitive Periods, and Later Adult Mental Health.","authors":"Joyce J Y Lin,Ruby Hickman,Justin Farmer,Michael Leung,Ian W Tang,Kaleigh McAlaine,Tracy Punshon,Brian P Jackson,Felicitas B Bidlack,Scott M Bartell,Joseph J Mangano,Marc G Weisskopf","doi":"10.1001/jamapsychiatry.2025.3012","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.3012","url":null,"abstract":"ImportanceEarly lead exposure is associated with psychological concerns in childhood, but less is known about sensitive periods of exposure or persistence into later adulthood.ObjectiveTo examine the association between prenatal and early postnatal lead exposure and risk of anxiety and depression in later adulthood.Design, Setting, and ParticipantsThis cohort study included participants from the Saint Louis Baby Tooth-Later Life Health Study (SLBT), who donated deciduous (baby) teeth in childhood during the 1950s through 1970s. SLBT participants were recontacted beginning in 2021 to complete health surveys and were masked to lead status. These data were analyzed from February 2025 through May 2025.ExposureLead exposure was measured in baby teeth across prenatal (approximately second trimester to birth, also split into second and approximately third trimesters), and early postnatal (birth to approximately 6 months old) periods.Main Outcomes and MeasuresSelf-reported depressive and anxiety symptoms were assessed via the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder Screener-7 (GAD-7) at a mean age of 62 (SD, 3.6) years. Outcomes were dichotomized using clinical cutoffs for major depressive disorder and generalized anxiety disorder. Secondary analyses treated outcomes as continuous symptom scores.ResultsOf 5131 SLBT participants, 718 (13.3%) had their baby teeth analyzed for lead (381 female [53%] and 334 male [47%]). In total, 695 and 697 participants responded to the PHQ-9 and GAD-7, respectively. The median (25th-75th percentile) combined tooth lead concentration was 1.34 (95% CI, 1.02-1.82) ppm. After adjusting for covariates, an IQR increase in combined tooth lead was associated with nearly 2 times the odds of later adulthood depression (odds ratio, 1.90; 95% CI, 1.20-2.99). The late prenatal period (approximately third trimester) appeared to be the most sensitive window (odds ratio, 1.55; 95% CI, 1.23-1.97). There was no association between early lead exposure and major later adulthood generalized anxiety disorder, but late prenatal and postnatal lead were associated with greater later adulthood anxiety symptoms.Conclusions and RelevanceThird-trimester lead exposure was associated with higher risk of major depressive disorder and anxiety symptoms in later adulthood. These findings emphasize the importance of factoring in later life health outcomes when considering the benefits of lead exposure interventions in childhood and suggest investment in screening and mental health services may be needed to address the long-term burden of historical lead exposure.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"17 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338869","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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