Pub Date : 2025-11-19DOI: 10.1001/jamapsychiatry.2025.3456
Satish Suhas,Guru S Gowda,Venkata Senthil Kumar Reddi
{"title":"Enough to Promote Changes to Current Management of Catatonia?-Reply.","authors":"Satish Suhas,Guru S Gowda,Venkata Senthil Kumar Reddi","doi":"10.1001/jamapsychiatry.2025.3456","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.3456","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"129 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145545263","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}
ImportanceClose social relationships are linked to improved individual health and even longevity. These effects are hypothesized to be mediated through improved neuroendocrine and immune functioning, particularly in individuals who engage in positive and affectionate interactions. However, systematic data examining these factors in humans are currently lacking.ObjectiveTo investigate the interacting effects of repeated intranasal oxytocin administration, a behavioral microintervention, and daily physical intimacy on neuroendocrine stress responses and dermatological wound healing.Design, Setting, and ParticipantsThis randomized clinical trial was a double-blind, randomized, placebo-controlled study whereby participants completed 3 laboratory visits and a 5-day ecological momentary assessment (EMA). During the first laboratory visit, participants received 4 small suction-blister wounds applied to their forearms. Data were collected from November 20, 2011, to July 25, 2013; final analyses were conducted from December 2023 to February 2025.InterventionsOver the following 7 days, participants were instructed to self-administer either oxytocin or a placebo twice daily and to engage in structured positive interaction (Partner Appreciation Task [PAT]) up to 3 times in total or not.Main Outcomes and MeasuresWound healing was assessed at 24 hours and 7 days after wounding. Throughout the week, participants collected saliva samples for cortisol analyses and reported their stress levels and experiences of partner interaction 6 times per day (5760 measurement points in total).ResultsThe volunteer sample was 80 healthy, heterosexual couples (N = 160 participants, mean [SD] age, 27.6 [5.0] years). Couples in the PAT condition who received daily oxytocin showed improved wound healing (b = -0.125, t286 = -1.983; P = .048). However, these effects were not consistently robust in sensitivity analyses (b = -0.090, t282 = -1.643; P = .10). Notably, the administration of oxytocin combined with daily affectionate touch (b = -0.038, t137 = -2.091; P = .04) and sexual activity (b = -0.145, t137 = -2.122; P = .04) was linked to a reduction in wound severity. These associations remained largely consistent in sensitivity analyses (affectionate touch: b = -0.037, t135 = -2.057; P = .04; sexual activity: b = -0.131, t135 = -1.900; P = .06). Additionally, greater sexual activity was associated with reduced daily cortisol levels (b = -373.084, t488 = -2.813; P = .005).Conclusions and RelevanceThis study found that intimate physical contact can reduce cortisol responses and, along with oxytocin administration, promote wound healing. These findings provide a foundation for future interventions that integrate relationship dynamics and neurohormonal modulation to improve health and recovery from illness.Trial RegistrationClinicalTrials.gov Identifier: NCT01594775.
密切的社会关系与个人健康状况的改善甚至寿命的延长有关。这些影响被假设是通过改善神经内分泌和免疫功能来调节的，特别是在那些参与积极和深情互动的个体中。然而，目前还缺乏在人类中检查这些因素的系统数据。目的探讨反复鼻内注射催产素、行为微干预和日常肢体亲密对神经内分泌应激反应和皮肤创面愈合的相互作用。设计、环境和参与者本随机临床试验是一项双盲、随机、安慰剂对照研究，参与者完成3次实验室访问和5天生态瞬时评估（EMA）。在第一次实验室访问期间，参与者在前臂上接受了4个小的吸吮性水泡伤口。数据采集时间为2011年11月20日至2013年7月25日；最终分析于2023年12月至2025年2月进行。干预措施在接下来的7天里，参与者被指示每天两次自我使用催产素或安慰剂，并参与结构化的积极互动（伴侣欣赏任务[PAT]），总共最多3次或不3次。主要观察结果和测量方法分别于伤口愈合后24小时和7天进行评估。整个星期，参与者收集唾液样本进行皮质醇分析，并报告他们的压力水平和伴侣互动的经历，每天6次（总共5760个测量点）。结果志愿者样本为80对健康的异性恋夫妇（N = 160），平均[SD]年龄27.6[5.0]岁。PAT组每日接受催产素治疗的夫妻伤口愈合改善（b = -0.125, t286 = -1.983; P = 0.048）。然而，这些效应在敏感性分析中并不稳定（b = -0.090, t282 = -1.643; P = .10）。值得注意的是，催产素与日常爱抚相结合(b = -0.038, t137 = -2.091；04)和性活动(b = -0.145, t137 = -2.122; P =。04)与伤口严重程度的降低有关。这些关联在敏感性分析中基本保持一致（深情触摸：b = -0.037, t135 = -2.057; P = 0.04；性行为：b = -0.131, t135 = -1.900; P = 0.06）。此外，更频繁的性活动与每日皮质醇水平降低相关（b = -373.084, t488 = -2.813; P = 0.005）。本研究发现，亲密的身体接触可以降低皮质醇的反应，并与催产素一起促进伤口愈合。这些发现为未来整合关系动力学和神经激素调节的干预提供了基础，以改善健康和从疾病中恢复。临床试验注册号：NCT01594775。
{"title":"Intranasal Oxytocin and Physical Intimacy for Dermatological Wound Healing and Neuroendocrine Stress: A Randomized Clinical Trial.","authors":"Ekaterina Schneider,Cristóbal Hernández,Robert Brock,Monika Eckstein,Guy Bodenmann,Markus Heinrichs,Ulrike Ehlert,Severin Läuchli,Beate Ditzen","doi":"10.1001/jamapsychiatry.2025.3705","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.3705","url":null,"abstract":"ImportanceClose social relationships are linked to improved individual health and even longevity. These effects are hypothesized to be mediated through improved neuroendocrine and immune functioning, particularly in individuals who engage in positive and affectionate interactions. However, systematic data examining these factors in humans are currently lacking.ObjectiveTo investigate the interacting effects of repeated intranasal oxytocin administration, a behavioral microintervention, and daily physical intimacy on neuroendocrine stress responses and dermatological wound healing.Design, Setting, and ParticipantsThis randomized clinical trial was a double-blind, randomized, placebo-controlled study whereby participants completed 3 laboratory visits and a 5-day ecological momentary assessment (EMA). During the first laboratory visit, participants received 4 small suction-blister wounds applied to their forearms. Data were collected from November 20, 2011, to July 25, 2013; final analyses were conducted from December 2023 to February 2025.InterventionsOver the following 7 days, participants were instructed to self-administer either oxytocin or a placebo twice daily and to engage in structured positive interaction (Partner Appreciation Task [PAT]) up to 3 times in total or not.Main Outcomes and MeasuresWound healing was assessed at 24 hours and 7 days after wounding. Throughout the week, participants collected saliva samples for cortisol analyses and reported their stress levels and experiences of partner interaction 6 times per day (5760 measurement points in total).ResultsThe volunteer sample was 80 healthy, heterosexual couples (N = 160 participants, mean [SD] age, 27.6 [5.0] years). Couples in the PAT condition who received daily oxytocin showed improved wound healing (b = -0.125, t286 = -1.983; P = .048). However, these effects were not consistently robust in sensitivity analyses (b = -0.090, t282 = -1.643; P = .10). Notably, the administration of oxytocin combined with daily affectionate touch (b = -0.038, t137 = -2.091; P = .04) and sexual activity (b = -0.145, t137 = -2.122; P = .04) was linked to a reduction in wound severity. These associations remained largely consistent in sensitivity analyses (affectionate touch: b = -0.037, t135 = -2.057; P = .04; sexual activity: b = -0.131, t135 = -1.900; P = .06). Additionally, greater sexual activity was associated with reduced daily cortisol levels (b = -373.084, t488 = -2.813; P = .005).Conclusions and RelevanceThis study found that intimate physical contact can reduce cortisol responses and, along with oxytocin administration, promote wound healing. These findings provide a foundation for future interventions that integrate relationship dynamics and neurohormonal modulation to improve health and recovery from illness.Trial RegistrationClinicalTrials.gov Identifier: NCT01594775.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"6 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145491506","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 : 2025-11-12DOI: 10.1001/jamapsychiatry.2025.3251
Sofie A Jacobsen,Marie W Petersen,Kaare B Wellnitz,Eva Ørnbøl,Thomas M Dantoft,Torben Jørgensen,Samuel A McLean,Lisbeth Frostholm,Tina B W Carstensen
ImportanceAn increasing number of sexual assaults (SAs) are reported. Prior studies show that SA is associated with functional somatic disorder (FSD).ObjectiveTo investigate whether SA is associated with the development of incident FSD, including 3 functional somatic syndromes (FSSs), chronic widespread pain (CWP), irritable bowel syndrome (IBS), and chronic fatigue (CF), over 5 years.Design, Setting, and ParticipantsA large prospective cohort study was conducted based on 5-year follow-up data (2017-2020) from the Danish Study of Functional Disorders (DanFunD). Incident FSD cases were identified through symptom questionnaires and diagnostic interviews among the population-based cohort aged 18 to 72 years from the western greater Copenhagen area. Completion of baseline SA measures and follow-up assessments was required for eligibility. Data analysis was conducted between January and September 2024.ExposuresSA was assessed at baseline via 2 items from the self-reported Cumulative Lifetime Adversity Measure, dichotomized into exposed and nonexposed.Main outcomes and measuresIncident FSD cases were defined using standardized criteria for single-organ and multiorgan FSD, CWP, IBS, and CF. Risk ratios (RRs) for FSD outcomes were estimated using generalized linear models adjusted for sex, emotional distress, life adversity or trauma, subjective social status, somatic comorbidities, neuroticism, health anxiety, perceived stress, and self-efficacy.ResultsAmong the 4229 adults (53.9% women; median age, 56 [IQR, 47-64] years) from the DanFunD cohort, SA was associated with incident FSD (RR, 1.69; 95% CI, 1.17-2.44), single-organ FSD (RR, 1.65; 95% CI, 1.14-2.38), multiorgan FSD (RR, 6.47; 95% CI, 1.93-21.75), FSS (RR, 1.54; 95% CI, 1.14-2.07), and CWP (RR, 1.89; 95% CI, 1.11-3.23), while findings with IBS (RR, 1.60; 95% CI, 0.81-3.16) and CF (RR, 1.47; 95% CI, 0.89-2.42) were not significant. Overall, those who reported exposure to SA experienced a significantly higher frequency of incident somatic symptoms than individuals not exposed to SA, including musculoskeletal, gastrointestinal, cardiopulmonary, and fatigue-related symptoms. Baseline emotional distress (eg, anxiety or depression) did not modify the findings for SA and FSD. Sensitivity analysis based on diagnostic interviews confirmed these results.Conclusions and RelevanceFindings of this cohort study suggest that SA may increase the risk of developing FSD, involving multiple body systems. Despite limitations from small case samples in some FSD subtypes, the pooled analysis underscores the high risk of FSD, emphasizing the critical need for further research and targeted interventions to address the long-term biopsychosocial consequences of SA.
{"title":"Functional Somatic Disorders in Individuals With a History of Sexual Assault.","authors":"Sofie A Jacobsen,Marie W Petersen,Kaare B Wellnitz,Eva Ørnbøl,Thomas M Dantoft,Torben Jørgensen,Samuel A McLean,Lisbeth Frostholm,Tina B W Carstensen","doi":"10.1001/jamapsychiatry.2025.3251","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.3251","url":null,"abstract":"ImportanceAn increasing number of sexual assaults (SAs) are reported. Prior studies show that SA is associated with functional somatic disorder (FSD).ObjectiveTo investigate whether SA is associated with the development of incident FSD, including 3 functional somatic syndromes (FSSs), chronic widespread pain (CWP), irritable bowel syndrome (IBS), and chronic fatigue (CF), over 5 years.Design, Setting, and ParticipantsA large prospective cohort study was conducted based on 5-year follow-up data (2017-2020) from the Danish Study of Functional Disorders (DanFunD). Incident FSD cases were identified through symptom questionnaires and diagnostic interviews among the population-based cohort aged 18 to 72 years from the western greater Copenhagen area. Completion of baseline SA measures and follow-up assessments was required for eligibility. Data analysis was conducted between January and September 2024.ExposuresSA was assessed at baseline via 2 items from the self-reported Cumulative Lifetime Adversity Measure, dichotomized into exposed and nonexposed.Main outcomes and measuresIncident FSD cases were defined using standardized criteria for single-organ and multiorgan FSD, CWP, IBS, and CF. Risk ratios (RRs) for FSD outcomes were estimated using generalized linear models adjusted for sex, emotional distress, life adversity or trauma, subjective social status, somatic comorbidities, neuroticism, health anxiety, perceived stress, and self-efficacy.ResultsAmong the 4229 adults (53.9% women; median age, 56 [IQR, 47-64] years) from the DanFunD cohort, SA was associated with incident FSD (RR, 1.69; 95% CI, 1.17-2.44), single-organ FSD (RR, 1.65; 95% CI, 1.14-2.38), multiorgan FSD (RR, 6.47; 95% CI, 1.93-21.75), FSS (RR, 1.54; 95% CI, 1.14-2.07), and CWP (RR, 1.89; 95% CI, 1.11-3.23), while findings with IBS (RR, 1.60; 95% CI, 0.81-3.16) and CF (RR, 1.47; 95% CI, 0.89-2.42) were not significant. Overall, those who reported exposure to SA experienced a significantly higher frequency of incident somatic symptoms than individuals not exposed to SA, including musculoskeletal, gastrointestinal, cardiopulmonary, and fatigue-related symptoms. Baseline emotional distress (eg, anxiety or depression) did not modify the findings for SA and FSD. Sensitivity analysis based on diagnostic interviews confirmed these results.Conclusions and RelevanceFindings of this cohort study suggest that SA may increase the risk of developing FSD, involving multiple body systems. Despite limitations from small case samples in some FSD subtypes, the pooled analysis underscores the high risk of FSD, emphasizing the critical need for further research and targeted interventions to address the long-term biopsychosocial consequences of SA.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"222 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145491504","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 : 2025-11-12DOI: 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}
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