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}
Pub Date : 2025-10-22DOI: 10.1001/jamapsychiatry.2025.3019
Ana Jelovac,Cathal McCaffrey,Masashi Terao,Enda Shanahan,Emma Whooley,Kelly McDonagh,Sarah McDonogh,Orlaith Loughran,Ellie Shackleton,Anna Igoe,Sarah Thompson,Enas Mohamed,Duyen Nguyen,Ciaran O'Neill,Cathal Walsh,Declan M McLoughlin
ImportanceSerial ketamine infusions are being increasingly adopted as off-label treatment for major depression in routine clinical practice, yet robust psychoactive placebo-controlled trial evidence for short- and long-term efficacy and safety remains limited.ObjectiveTo assess antidepressant efficacy, safety, tolerability, cost-effectiveness, and quality of life during and after serial ketamine infusions compared with midazolam as an adjunct to usual inpatient care.Design, Setting, and ParticipantsThe KARMA-Dep 2 trial was an investigator-led, double-blind, randomized, midazolam-controlled, pragmatic trial conducted at an academic center in Ireland between September 2021 and August 2024. Participants included adults (≥18 years) hospitalized with a DSM-5 major depressive episode (unipolar or bipolar) and baseline Montgomery-Åsberg Depression Rating Scale (MADRS) score ≥20.InterventionsParticipants were randomized 1:1 to receive up to 8 twice-weekly intravenous infusions of either ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg) as an adjunct to usual-care pharmacotherapy and other aspects of routine inpatient psychiatric care. Participants were followed up for 6 months.Main Outcomes and MeasuresThe primary outcome was change in depression symptom severity measured by the observer-rated MADRS score from baseline to end of treatment. Secondary outcomes included self-reported depression severity, safety, tolerability, health care costs, and quality of life.ResultsOf 65 randomized participants (mean [SD] age, 53.5 [18.6] years; 37 [59.7%] male), 62 were included in the final analysis. In the analysis of primary outcome, end-of-treatment MADRS scores did not significantly differ between the ketamine and midazolam groups (adjusted mean difference, -3.16 points, 95% CI, -8.54 to 2.22; P = .25; Cohen d, -0.29). Similarly, there was no significant between-group difference between Quick Inventory of Depressive Symptoms, Self-Report, scores (adjusted mean difference, -0.002; 95% CI, -2.71 to 2.71; P > .99; Cohen d, -0.0004). There were no significant between-group differences on other secondary outcomes, including cognition, cost-effectiveness, or quality of life. Most patients and raters accurately guessed treatment allocation.Conclusions and RelevanceSerial adjunctive ketamine infusions were not more effective than serial midazolam infusions in reducing depressive symptoms in inpatients receiving usual psychiatric care.Trial RegistrationClinicalTrials.gov Identifier: NCT04939649.
{"title":"Serial Ketamine Infusions as Adjunctive Therapy to Inpatient Care for Depression: The KARMA-Dep 2 Randomized Clinical Trial.","authors":"Ana Jelovac,Cathal McCaffrey,Masashi Terao,Enda Shanahan,Emma Whooley,Kelly McDonagh,Sarah McDonogh,Orlaith Loughran,Ellie Shackleton,Anna Igoe,Sarah Thompson,Enas Mohamed,Duyen Nguyen,Ciaran O'Neill,Cathal Walsh,Declan M McLoughlin","doi":"10.1001/jamapsychiatry.2025.3019","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.3019","url":null,"abstract":"ImportanceSerial ketamine infusions are being increasingly adopted as off-label treatment for major depression in routine clinical practice, yet robust psychoactive placebo-controlled trial evidence for short- and long-term efficacy and safety remains limited.ObjectiveTo assess antidepressant efficacy, safety, tolerability, cost-effectiveness, and quality of life during and after serial ketamine infusions compared with midazolam as an adjunct to usual inpatient care.Design, Setting, and ParticipantsThe KARMA-Dep 2 trial was an investigator-led, double-blind, randomized, midazolam-controlled, pragmatic trial conducted at an academic center in Ireland between September 2021 and August 2024. Participants included adults (≥18 years) hospitalized with a DSM-5 major depressive episode (unipolar or bipolar) and baseline Montgomery-Åsberg Depression Rating Scale (MADRS) score ≥20.InterventionsParticipants were randomized 1:1 to receive up to 8 twice-weekly intravenous infusions of either ketamine (0.5 mg/kg) or midazolam (0.045 mg/kg) as an adjunct to usual-care pharmacotherapy and other aspects of routine inpatient psychiatric care. Participants were followed up for 6 months.Main Outcomes and MeasuresThe primary outcome was change in depression symptom severity measured by the observer-rated MADRS score from baseline to end of treatment. Secondary outcomes included self-reported depression severity, safety, tolerability, health care costs, and quality of life.ResultsOf 65 randomized participants (mean [SD] age, 53.5 [18.6] years; 37 [59.7%] male), 62 were included in the final analysis. In the analysis of primary outcome, end-of-treatment MADRS scores did not significantly differ between the ketamine and midazolam groups (adjusted mean difference, -3.16 points, 95% CI, -8.54 to 2.22; P = .25; Cohen d, -0.29). Similarly, there was no significant between-group difference between Quick Inventory of Depressive Symptoms, Self-Report, scores (adjusted mean difference, -0.002; 95% CI, -2.71 to 2.71; P > .99; Cohen d, -0.0004). There were no significant between-group differences on other secondary outcomes, including cognition, cost-effectiveness, or quality of life. Most patients and raters accurately guessed treatment allocation.Conclusions and RelevanceSerial adjunctive ketamine infusions were not more effective than serial midazolam infusions in reducing depressive symptoms in inpatients receiving usual psychiatric care.Trial RegistrationClinicalTrials.gov Identifier: NCT04939649.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"139 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338871","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.2025.2958
Alexandra Moussa-Tooks,Adam Kuczynski,Leah Gilbertson,Sarah L Kopelovich
{"title":"Toward a New Standard in Inpatient Psychiatry-Integration of Clinical Psychologists.","authors":"Alexandra Moussa-Tooks,Adam Kuczynski,Leah Gilbertson,Sarah L Kopelovich","doi":"10.1001/jamapsychiatry.2025.2958","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.2958","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"108 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338870","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 : 2025-10-21DOI: 10.1001/jamapsychiatry.2025.3444
Fenfen Ge,Yue Wang,Esben Agerbo,Ole Köhler-Forsberg,Cynthia M Bulik,Liselotte Vogdrup Petersen,Bjarni Jóhann Vilhjálmsson
ImportanceNot all individuals who die by suicide have a history of nonfatal suicide attempt (SA); however, little is known about the extent to which the genetic and environmental etiologies of SA and suicide are shared or distinct.ObjectiveTo examine shared and distinct risk factors for SA and suicide, focusing on clinically diagnosed health conditions and genetic factors.Design, Setting, and ParticipantsFor health conditions, a nested case-control study was performed using data from the Danish registers. For genetic factors, a case-control analysis framework was used, with individual genotypes retrieved from the iPSYCH2015 dataset, which was nested within the entire Danish population. Individuals older than 10 years were included to minimize the risk of misclassification for SA and suicide. Data were analyzed from January 2024 to April 2025.ExposuresTwenty-eight health conditions and 35 polygenic scores (PGSs) for complex traits.Main Outcomes and MeasuresThe primary outcomes were SA, suicide, and cumulative SA burden. Associations between health conditions and the risk of SA and suicide were assessed using conditional logistic regression. PGSs for complex traits were calculated using LDpred2-auto, and their associations with SA and suicide were evaluated via logistic regression. To assess whether effect sizes differed significantly between SA and suicide, bayesian model-based classification and Cochran Q test were applied.ResultsA total of 81 713 cases of SA (50 512 [61.8%] female; mean [SD] age, 32.3 [14.9] years), with 408 490 age-matched controls (252 525 [61.8%] female; mean [SD] age, 32.3 [14.9] years), and 9362 cases of suicide (2360 [25.2%] female; mean [SD] age, 45.1 [14.6] years), along with 46 749 matched controls (11 796 [25.2%] female; mean [SD] age, 45.1 [14.6] years) who were alive at the date of the case's death, were included in the health conditions analysis. The PGS analysis included 8221 cases of SA (5944 [72.3%] female; mean [SD] age, 19.7 [4.4] years) and 225 cases of suicide (80 [35.6%] female; mean [SD] age, 24.6 [5.0] years). Chronic diseases (eg, dyslipidemia or hearing problems) showed stronger associations with SA, while severe conditions (eg, cancer) were more strongly associated with suicide. Suicide was influenced only by PGSs for mental disorders, whereas SA was associated with both psychiatric and broader health-related genetic risk factors. Notably, dose-response associations were observed for most health conditions and PGSs in relation to cumulative SA burden.Conclusions and RelevanceA broad range of health conditions and genetic factors were associated with increased risk of both outcomes; however, their shared and distinct risk factors suggest that SA and death by suicide are not solely differentiated by liability severity.
{"title":"Contrasting Risk Profiles for Suicide Attempt and Suicide Using Danish Registers and Genetic Data.","authors":"Fenfen Ge,Yue Wang,Esben Agerbo,Ole Köhler-Forsberg,Cynthia M Bulik,Liselotte Vogdrup Petersen,Bjarni Jóhann Vilhjálmsson","doi":"10.1001/jamapsychiatry.2025.3444","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.3444","url":null,"abstract":"ImportanceNot all individuals who die by suicide have a history of nonfatal suicide attempt (SA); however, little is known about the extent to which the genetic and environmental etiologies of SA and suicide are shared or distinct.ObjectiveTo examine shared and distinct risk factors for SA and suicide, focusing on clinically diagnosed health conditions and genetic factors.Design, Setting, and ParticipantsFor health conditions, a nested case-control study was performed using data from the Danish registers. For genetic factors, a case-control analysis framework was used, with individual genotypes retrieved from the iPSYCH2015 dataset, which was nested within the entire Danish population. Individuals older than 10 years were included to minimize the risk of misclassification for SA and suicide. Data were analyzed from January 2024 to April 2025.ExposuresTwenty-eight health conditions and 35 polygenic scores (PGSs) for complex traits.Main Outcomes and MeasuresThe primary outcomes were SA, suicide, and cumulative SA burden. Associations between health conditions and the risk of SA and suicide were assessed using conditional logistic regression. PGSs for complex traits were calculated using LDpred2-auto, and their associations with SA and suicide were evaluated via logistic regression. To assess whether effect sizes differed significantly between SA and suicide, bayesian model-based classification and Cochran Q test were applied.ResultsA total of 81 713 cases of SA (50 512 [61.8%] female; mean [SD] age, 32.3 [14.9] years), with 408 490 age-matched controls (252 525 [61.8%] female; mean [SD] age, 32.3 [14.9] years), and 9362 cases of suicide (2360 [25.2%] female; mean [SD] age, 45.1 [14.6] years), along with 46 749 matched controls (11 796 [25.2%] female; mean [SD] age, 45.1 [14.6] years) who were alive at the date of the case's death, were included in the health conditions analysis. The PGS analysis included 8221 cases of SA (5944 [72.3%] female; mean [SD] age, 19.7 [4.4] years) and 225 cases of suicide (80 [35.6%] female; mean [SD] age, 24.6 [5.0] years). Chronic diseases (eg, dyslipidemia or hearing problems) showed stronger associations with SA, while severe conditions (eg, cancer) were more strongly associated with suicide. Suicide was influenced only by PGSs for mental disorders, whereas SA was associated with both psychiatric and broader health-related genetic risk factors. Notably, dose-response associations were observed for most health conditions and PGSs in relation to cumulative SA burden.Conclusions and RelevanceA broad range of health conditions and genetic factors were associated with increased risk of both outcomes; however, their shared and distinct risk factors suggest that SA and death by suicide are not solely differentiated by liability severity.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"101 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338538","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 : 2025-10-15DOI: 10.1001/jamapsychiatry.2025.2962
John C Fortney,Debra L Kaysen,Charles C Engel,Joseph M Cerimele,John P Nolan,Erin Chase,Brittany E Blanchard,Stephanie Hauge,Jared Bechtel,Ashley Taylor,Ron Acierno,Nancy Nagel,Rebecca K Sripada,Jacob T Painter,Bryann B DeBeer,Anya Zimberoff,Ellen J Bluett,Alan R Teo,Leslie A Morland,Kathleen Grubbs,Denise M Sloan,Brian P Marx,Patrick J Heagerty
ImportanceThere have only been 3 efficacy trials reporting head-to-head comparisons of pharmacotherapy and trauma-focused psychotherapy for posttraumatic stress disorder (PTSD), and none were conducted in primary care. In addition, few trials have examined treatment sequences for patients not responding to an initial treatment.ObjectiveTo test the hypothesis that (1) brief trauma-focused psychotherapy (written exposure therapy [WET]) is more effective than a choice of 3 selective serotonin reuptake inhibitors (SSRIs; ie, sertraline, fluoxetine, or paroxetine) and (2) WET augmentation is more effective than switching to the serotonin-norepinephrine reuptake inhibitor (SNRI) venlafaxine for those not responding to an SSRI.Design, Setting, and ParticipantsThis was a pragmatic comparative effectiveness trial conducted from April 2021 to June 2024 that randomized primary care patients to 1 of 3 treatment sequences: (1) SSRI followed by WET augmentation, (2) SSRI followed by switch to SNRI, or (3) WET followed by SSRI. Effectiveness in this pragmatic trial depends on treatment engagement and treatment fidelity. The study included patients meeting clinical criteria for PTSD from primary care clinics of 7 federally qualified health centers and 8 Department of Veterans Affairs medical centers.InterventionsSSRI followed by WET augmentation, SSRI followed by switch to SNRI, or WET followed by SSRI.Main Outcomes and MeasuresPTSD symptom severity, as measured by the DSM-5 PTSD Checklist (PCL-5).ResultsA total of 700 patients (mean [SD] age, 45.1 [15.4] years; 368 men [62.1%]). The mean (SD) baseline PCL-5 score was 52.8 (11.1), indicating considerable symptom severity. At 4 months, 144 of 278 patients (51.8%) randomized to an SSRI were adherent and reported a 14.0-point PCL-5 decrease, whereas 11 of 352 patients (31.5%) randomized to WET completed all sessions and reported a 12.1-point decrease. There was no significant between-group difference (adjusted mean difference [MD], 1.79; 95% CI, -0.76 to 4.34; P = .17). For the 122 of 295 patients (41.4%) randomized to an SSRI who did not respond to treatment, those randomized to switch to the SNRI reported a 9.2-point PCL-5 decrease compared with a 2.3-point decrease for those randomized to WET augmentation, which was a statistically significant between-group difference (adjusted MD, 10.19; 95% CI, 4.97-15.41; P < .001).Conclusions and RelevanceStudy results showed that treatment of PTSD in primary care with either SSRIs or WET was feasible and effective. For patients not responding to an SSRI, switching to an SNRI may be more effective than WET augmentation.Trial RegistrationClinicalTrials.gov Identifier: NCT04597190.
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