Pub Date : 2025-01-22DOI: 10.1001/jamapsychiatry.2024.4483
Artur Menegaz de Almeida, Francisco Cezar Aquino Moraes, Francinny Alves Kelly
{"title":"Bright Light Therapy for Nonseasonal Depressive Disorders-Reply.","authors":"Artur Menegaz de Almeida, Francisco Cezar Aquino Moraes, Francinny Alves Kelly","doi":"10.1001/jamapsychiatry.2024.4483","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.4483","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":""},"PeriodicalIF":22.5,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005785","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 : 2025-01-22DOI: 10.1001/jamapsychiatry.2024.4475
Beth Han, Wilson M Compton, Emily B Einstein, Nora D Volkow
{"title":"Medically Recommended vs Nonmedical Cannabis Use Among US Adults.","authors":"Beth Han, Wilson M Compton, Emily B Einstein, Nora D Volkow","doi":"10.1001/jamapsychiatry.2024.4475","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.4475","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":""},"PeriodicalIF":22.5,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005787","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 : 2025-01-22DOI: 10.1001/jamapsychiatry.2024.4462
Jennifer Y F Lau, Stefan Priebe, Craig Morgan
{"title":"Social Health and Serious Mental Illness-A Step Forward?","authors":"Jennifer Y F Lau, Stefan Priebe, Craig Morgan","doi":"10.1001/jamapsychiatry.2024.4462","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.4462","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":""},"PeriodicalIF":22.5,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005789","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 : 2025-01-22DOI: 10.1001/jamapsychiatry.2024.4465
Yanli Zhang-James, John Paliakkara, Joshua Schaeffer, Joseph Strayhorn, Stephen V Faraone
<p><strong>Importance: </strong>Intermittent explosive disorder (IED) is an understudied psychiatric condition marked by impulsive aggression and poorly regulated emotional control, often resulting in interpersonal and societal consequences. Better understanding of comorbidities can improve screening, diagnosis, and treatment.</p><p><strong>Objective: </strong>To investigate the prevalence of IED and its associations with psychiatric, neurological, and somatic disorders.</p><p><strong>Design, setting, and participants: </strong>In this cohort study, matched groups of patients with and without IED were identified from the TriNetX Research Network (dated January 31, 2024). Electronic medical record data were analyzed. The mean (SD) time from the first to last known visits was 4.8 (5.4) years.</p><p><strong>Exposure: </strong>Lifetime diagnosis of IED.</p><p><strong>Main outcomes and measures: </strong>Main outcomes were International Statistical Classification of Diseases, Tenth Revision, Clinical Modification diagnostic categories and root codes. Cox proportional hazard models were used to estimate and compare probabilities of acquiring other diagnoses. Key measures include the numbers and proportions of patients with these diagnoses and adjusted hazard ratios (HRs) for IED.</p><p><strong>Results: </strong>Overall, 30 357 individuals with IED and 30 357 demographically matched controls were included. In each group, 21 313 (70%) were male, with a mean (SD) age at the first visit 26 (17) years. Despite only 0.03% of the total patient population having an IED diagnosis, extensive comorbidities with psychiatric, neurological, and somatic conditions were found. A notable 95.7% of individuals with IED (29 054 individuals) had another psychiatric diagnosis. All psychiatric subcategories and 92% of the psychiatric diagnoses were significantly associated with IED, with HRs ranging from 2.1 (95% CI, 2.0-2.2) for substance use disorder to 76.6 (95% CI, 65.4-89.6) for disorders of adult personality and behavior (excluding IED). Among neurological conditions, neurodegenerative diseases (HR, 5.0; 95% CI, 4.1-6.1) and epilepsy (HR, 4.9; 95% CI, 4.3-5.6) had the highest HRs, followed by movement disorders (HR, 3.1; 95% CI, 2.8-3.5), cerebral palsy (HR, 2.6; 95% CI, 2.2-3.0), and sleep disorders (HR, 2.2; 95% CI, 2.1-2.3). Significant associations with IED were also observed for many somatic diseases, including obesity (HR, 1.6; 95% CI, 1.5-1.7), hyperlipidemia (HR, 1.5; 95% CI, 1.4-1.5), hypertension (HR, 1.6; 95% CI, 1.5-1.7), and gastroesophageal reflux disease (HR, 1.7; 95% CI, 1.7-1.9).</p><p><strong>Conclusion and relevance: </strong>These findings highlight the extensive comorbidities between IED and psychiatric, neurological, and somatic disorders, emphasizing the need for integrated diagnostic and treatment approaches addressing both psychological and physical health aspects of IED. Limitations related to reliance on medical records and low diagnostic rat
{"title":"Psychiatric, Neurological, and Somatic Comorbidities in Intermittent Explosive Disorder.","authors":"Yanli Zhang-James, John Paliakkara, Joshua Schaeffer, Joseph Strayhorn, Stephen V Faraone","doi":"10.1001/jamapsychiatry.2024.4465","DOIUrl":"10.1001/jamapsychiatry.2024.4465","url":null,"abstract":"<p><strong>Importance: </strong>Intermittent explosive disorder (IED) is an understudied psychiatric condition marked by impulsive aggression and poorly regulated emotional control, often resulting in interpersonal and societal consequences. Better understanding of comorbidities can improve screening, diagnosis, and treatment.</p><p><strong>Objective: </strong>To investigate the prevalence of IED and its associations with psychiatric, neurological, and somatic disorders.</p><p><strong>Design, setting, and participants: </strong>In this cohort study, matched groups of patients with and without IED were identified from the TriNetX Research Network (dated January 31, 2024). Electronic medical record data were analyzed. The mean (SD) time from the first to last known visits was 4.8 (5.4) years.</p><p><strong>Exposure: </strong>Lifetime diagnosis of IED.</p><p><strong>Main outcomes and measures: </strong>Main outcomes were International Statistical Classification of Diseases, Tenth Revision, Clinical Modification diagnostic categories and root codes. Cox proportional hazard models were used to estimate and compare probabilities of acquiring other diagnoses. Key measures include the numbers and proportions of patients with these diagnoses and adjusted hazard ratios (HRs) for IED.</p><p><strong>Results: </strong>Overall, 30 357 individuals with IED and 30 357 demographically matched controls were included. In each group, 21 313 (70%) were male, with a mean (SD) age at the first visit 26 (17) years. Despite only 0.03% of the total patient population having an IED diagnosis, extensive comorbidities with psychiatric, neurological, and somatic conditions were found. A notable 95.7% of individuals with IED (29 054 individuals) had another psychiatric diagnosis. All psychiatric subcategories and 92% of the psychiatric diagnoses were significantly associated with IED, with HRs ranging from 2.1 (95% CI, 2.0-2.2) for substance use disorder to 76.6 (95% CI, 65.4-89.6) for disorders of adult personality and behavior (excluding IED). Among neurological conditions, neurodegenerative diseases (HR, 5.0; 95% CI, 4.1-6.1) and epilepsy (HR, 4.9; 95% CI, 4.3-5.6) had the highest HRs, followed by movement disorders (HR, 3.1; 95% CI, 2.8-3.5), cerebral palsy (HR, 2.6; 95% CI, 2.2-3.0), and sleep disorders (HR, 2.2; 95% CI, 2.1-2.3). Significant associations with IED were also observed for many somatic diseases, including obesity (HR, 1.6; 95% CI, 1.5-1.7), hyperlipidemia (HR, 1.5; 95% CI, 1.4-1.5), hypertension (HR, 1.6; 95% CI, 1.5-1.7), and gastroesophageal reflux disease (HR, 1.7; 95% CI, 1.7-1.9).</p><p><strong>Conclusion and relevance: </strong>These findings highlight the extensive comorbidities between IED and psychiatric, neurological, and somatic disorders, emphasizing the need for integrated diagnostic and treatment approaches addressing both psychological and physical health aspects of IED. Limitations related to reliance on medical records and low diagnostic rat","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":""},"PeriodicalIF":22.5,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005788","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 : 2025-01-22DOI: 10.1001/jamapsychiatry.2024.4573
Dost Öngür, Roy H Perlis
{"title":"Announcing \"Technology and Psychiatry\" and Expanding Evidence-Based Comments and Reviews in JAMA Psychiatry.","authors":"Dost Öngür, Roy H Perlis","doi":"10.1001/jamapsychiatry.2024.4573","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.4573","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":""},"PeriodicalIF":22.5,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005783","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 : 2025-01-22DOI: 10.1001/jamapsychiatry.2024.4305
Wietse A Wiels, Julie E Oomens, Sebastiaan Engelborghs, Chris Baeken, Christine A F von Arnim, Mercè Boada, Mira Didic, Bruno Dubois, Tormod Fladby, Wiesje M van der Flier, Giovanni B Frisoni, Lutz Fröhlich, Kiran Dip Gill, Timo Grimmer, Helmut Hildebrandt, Jakub Hort, Yoshiaki Itoh, Takeshi Iwatsubo, Aleksandra Klimkowicz-Mrowiec, Dong Young Lee, Alberto Lleó, Pablo Martinez-Lage, Alexandre de Mendonça, Philipp T Meyer, Elisabeth N Kapaki, Piero Parchi, Matteo Pardini, Lucilla Parnetti, Julius Popp, Lorena Rami, Eric M Reiman, Juha O Rinne, Karen M Rodrigue, Pascual Sánchez-Juan, Isabel Santana, Marie Sarazin, Nikolaos Scarmeas, Ingmar Skoog, Peter J Snyder, Reisa A Sperling, Sylvia Villeneuve, Anders Wallin, Jens Wiltfang, Henrik Zetterberg, Rik Ossenkoppele, Frans R J Verhey, Stephanie J B Vos, Pieter Jelle Visser, Willemijn J Jansen, Daniel Alcolea, Daniele Altomare, Simone Baiardi, Ines Baldeiras, Randall J Bateman, Kaj Blennow, Michel Bottlaender, Anouk den Braber, Mark A van Buchem, Min Soo Byun, Jirí Cerman, Kewei Chen, Elena Chipi, Gregory S Day, Alexander Drzezga, Marie Eckerström, Laura L Ekblad, Stéphane Epelbaum, Stefan Förster, Juan Fortea, Yvonne Freund-Levi, Lars Frings, Eric Guedj, Lucrezia Hausner, Sabine Hellwig, Edward D Huey, Julio F Jiménez-Bonilla, Keith A Johnson, Ane Iriondo Juaristi, Ramesh Kandimalla, George Paraskevas, Silke Kern, Bjørn-Eivind S Kirsebom, Johannes Kornhuber, Julien Lagarde, Susan M Landau, Nienke Legdeur, Jorge J Llibre Guerra, Nancy N Maserejian, Marta Marquié, Shinobu Minatani, Silvia Daniela Morbelli, Barbara Mroczko, Eva Ntanasi, Catarina Resende de Oliveira, Pauline Olivieri, Adelina Orellana, Richard J Perrin, Oliver Peters, Sudesh Prabhakar, Inez H Ramakers, Eloy Rodríguez-Rodriguez, Agustín Ruiz, Eckart Rüther, Per Selnes, Dina Silva, Hilkka Soininen, Luiza Spiru, Akitoshi Takeda, Marc Teichmann, Betty M Tijms, Charlotte E Teunissen, Loisa I Thompson, Jonathan Vogelgsangs, Jonathan Vöglein, Gunhild Waldemar, Åsa K Wallin, Mary Yannakoulia, Dahyun Yi, Anna Zettergren
<p><strong>Importance: </strong>Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology.</p><p><strong>Objective: </strong>To examine the association between depressive symptoms and amyloid pathology and its dependency on age, sex, education, and APOE genotype in older individuals without dementia.</p><p><strong>Design, setting, and participants: </strong>Cross-sectional analyses were performed using data from the Amyloid Biomarker Study data pooling initiative. Data from 49 research, population-based, and memory clinic studies were pooled and harmonized. The Amyloid Biomarker Study has been collecting data since 2012 and data collection is ongoing. At the time of analysis, 95 centers were included in the Amyloid Biomarker Study. The study included 9746 individuals with normal cognition (NC) and 3023 participants with mild cognitive impairment (MCI) aged between 34 and 100 years for whom data on amyloid biomarkers, presence of depressive symptoms, and age were available. Data were analyzed from December 2022 to February 2024.</p><p><strong>Main outcomes and measures: </strong>Amyloid-β1-42 levels in cerebrospinal fluid or amyloid positron emission tomography scans were used to determine presence or absence of amyloid pathology. Presence of depressive symptoms was determined on the basis of validated depression rating scale scores, evidence of a current clinical diagnosis of depression, or self-reported depressive symptoms.</p><p><strong>Results: </strong>In individuals with NC (mean [SD] age, 68.6 [8.9] years; 5664 [58.2%] female; 3002 [34.0%] APOE ε4 carriers; 937 [9.6%] had depressive symptoms; 2648 [27.2%] had amyloid pathology), the presence of depressive symptoms was not associated with amyloid pathology (odds ratio [OR], 1.13; 95% CI, 0.90-1.40; P = .29). In individuals with MCI (mean [SD] age, 70.2 [8.7] years; 1481 [49.0%] female; 1046 [44.8%] APOE ε4 carriers; 824 [27.3%] had depressive symptoms; 1668 [55.8%] had amyloid pathology), the presence of depressive symptoms was associated with a lower likelihood of amyloid pathology (OR, 0.73; 95% CI 0.61-0.89; P = .001). When considering subgroup effects, in individuals with NC, the presence of depressive symptoms was associated with a higher frequency of amyloid pathology in APOE ε4 noncarriers (mean difference, 5.0%; 95% CI 1.0-9.0; P = .02) but not in APOE ε4 carriers. This was not the case in individuals with MCI.</p><p><strong>Conclusions and relevance: </strong>Depressive symptoms were not consistently associated with a higher frequency of amyloid pathology in participants with NC and were associated with a lower likelihood of amyloid pathology in participants with MCI. These findings were not influenced by age, sex, or education level. Mechanisms other than amyloid accumula
重要性：抑郁症状与老年人认知能力下降有关。潜在机制的不确定性阻碍了诊断和治疗的努力。这项大规模的研究旨在阐明抑郁症状与淀粉样蛋白病理之间的关系。目的：探讨老年痴呆患者抑郁症状与淀粉样蛋白病理的关系及其与年龄、性别、教育程度和APOE基因型的关系。设计、设置和参与者：使用淀粉样蛋白生物标志物研究数据池计划的数据进行横断面分析。来自49项研究、基于人群的研究和记忆临床研究的数据被汇总和协调。淀粉样蛋白生物标志物研究自2012年以来一直在收集数据，数据收集仍在进行中。在分析时，95个中心被纳入淀粉样蛋白生物标志物研究。该研究包括9746名正常认知（NC）个体和3023名轻度认知障碍（MCI）参与者，年龄在34至100岁之间，他们的淀粉样蛋白生物标志物、抑郁症状的存在和年龄均可获得。数据分析时间为2022年12月至2024年2月。主要结果和测量：脑脊液中淀粉样蛋白β1-42水平或淀粉样蛋白正电子发射断层扫描用于确定淀粉样蛋白病理的存在或不存在。抑郁症状的存在是根据有效的抑郁评定量表得分、当前临床诊断抑郁的证据或自我报告的抑郁症状来确定的。结果：NC患者的平均[SD]年龄为68.6[8.9]岁；女性5664人[58.2%]；3002个[34.0%]APOE ε4携带者；有抑郁症状937例（9.6%）；2648例（27.2%）有淀粉样蛋白病理)，抑郁症状的存在与淀粉样蛋白病理无关(优势比[OR]， 1.13；95% ci, 0.90-1.40；p = .29)。轻度认知障碍患者的平均[SD]年龄为70.2[8.7]岁；女性1481人[49.0%]；APOE ε4携带者1046例[44.8%]；824人（27.3%）有抑郁症状；1668例[55.8%]有淀粉样蛋白病理)，抑郁症状的存在与淀粉样蛋白病理的可能性较低相关(OR, 0.73；95% ci 0.61-0.89；p = .001)。当考虑亚组效应时，在NC个体中，抑郁症状的存在与APOE ε4非携带者淀粉样蛋白病理的较高频率相关(平均差异为5.0%；95% ci 1.0-9.0；P = .02)，但APOE ε4携带者无明显差异。这与轻度认知障碍患者的情况不同。结论和相关性：抑郁症状与NC患者淀粉样蛋白病理的高频率并不一致相关，而与MCI患者淀粉样蛋白病理的低可能性相关。这些发现不受年龄、性别或教育水平的影响。淀粉样蛋白积累以外的机制可能通常是晚年抑郁症状的基础。
{"title":"Depressive Symptoms and Amyloid Pathology.","authors":"Wietse A Wiels, Julie E Oomens, Sebastiaan Engelborghs, Chris Baeken, Christine A F von Arnim, Mercè Boada, Mira Didic, Bruno Dubois, Tormod Fladby, Wiesje M van der Flier, Giovanni B Frisoni, Lutz Fröhlich, Kiran Dip Gill, Timo Grimmer, Helmut Hildebrandt, Jakub Hort, Yoshiaki Itoh, Takeshi Iwatsubo, Aleksandra Klimkowicz-Mrowiec, Dong Young Lee, Alberto Lleó, Pablo Martinez-Lage, Alexandre de Mendonça, Philipp T Meyer, Elisabeth N Kapaki, Piero Parchi, Matteo Pardini, Lucilla Parnetti, Julius Popp, Lorena Rami, Eric M Reiman, Juha O Rinne, Karen M Rodrigue, Pascual Sánchez-Juan, Isabel Santana, Marie Sarazin, Nikolaos Scarmeas, Ingmar Skoog, Peter J Snyder, Reisa A Sperling, Sylvia Villeneuve, Anders Wallin, Jens Wiltfang, Henrik Zetterberg, Rik Ossenkoppele, Frans R J Verhey, Stephanie J B Vos, Pieter Jelle Visser, Willemijn J Jansen, Daniel Alcolea, Daniele Altomare, Simone Baiardi, Ines Baldeiras, Randall J Bateman, Kaj Blennow, Michel Bottlaender, Anouk den Braber, Mark A van Buchem, Min Soo Byun, Jirí Cerman, Kewei Chen, Elena Chipi, Gregory S Day, Alexander Drzezga, Marie Eckerström, Laura L Ekblad, Stéphane Epelbaum, Stefan Förster, Juan Fortea, Yvonne Freund-Levi, Lars Frings, Eric Guedj, Lucrezia Hausner, Sabine Hellwig, Edward D Huey, Julio F Jiménez-Bonilla, Keith A Johnson, Ane Iriondo Juaristi, Ramesh Kandimalla, George Paraskevas, Silke Kern, Bjørn-Eivind S Kirsebom, Johannes Kornhuber, Julien Lagarde, Susan M Landau, Nienke Legdeur, Jorge J Llibre Guerra, Nancy N Maserejian, Marta Marquié, Shinobu Minatani, Silvia Daniela Morbelli, Barbara Mroczko, Eva Ntanasi, Catarina Resende de Oliveira, Pauline Olivieri, Adelina Orellana, Richard J Perrin, Oliver Peters, Sudesh Prabhakar, Inez H Ramakers, Eloy Rodríguez-Rodriguez, Agustín Ruiz, Eckart Rüther, Per Selnes, Dina Silva, Hilkka Soininen, Luiza Spiru, Akitoshi Takeda, Marc Teichmann, Betty M Tijms, Charlotte E Teunissen, Loisa I Thompson, Jonathan Vogelgsangs, Jonathan Vöglein, Gunhild Waldemar, Åsa K Wallin, Mary Yannakoulia, Dahyun Yi, Anna Zettergren","doi":"10.1001/jamapsychiatry.2024.4305","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.4305","url":null,"abstract":"<p><strong>Importance: </strong>Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology.</p><p><strong>Objective: </strong>To examine the association between depressive symptoms and amyloid pathology and its dependency on age, sex, education, and APOE genotype in older individuals without dementia.</p><p><strong>Design, setting, and participants: </strong>Cross-sectional analyses were performed using data from the Amyloid Biomarker Study data pooling initiative. Data from 49 research, population-based, and memory clinic studies were pooled and harmonized. The Amyloid Biomarker Study has been collecting data since 2012 and data collection is ongoing. At the time of analysis, 95 centers were included in the Amyloid Biomarker Study. The study included 9746 individuals with normal cognition (NC) and 3023 participants with mild cognitive impairment (MCI) aged between 34 and 100 years for whom data on amyloid biomarkers, presence of depressive symptoms, and age were available. Data were analyzed from December 2022 to February 2024.</p><p><strong>Main outcomes and measures: </strong>Amyloid-β1-42 levels in cerebrospinal fluid or amyloid positron emission tomography scans were used to determine presence or absence of amyloid pathology. Presence of depressive symptoms was determined on the basis of validated depression rating scale scores, evidence of a current clinical diagnosis of depression, or self-reported depressive symptoms.</p><p><strong>Results: </strong>In individuals with NC (mean [SD] age, 68.6 [8.9] years; 5664 [58.2%] female; 3002 [34.0%] APOE ε4 carriers; 937 [9.6%] had depressive symptoms; 2648 [27.2%] had amyloid pathology), the presence of depressive symptoms was not associated with amyloid pathology (odds ratio [OR], 1.13; 95% CI, 0.90-1.40; P = .29). In individuals with MCI (mean [SD] age, 70.2 [8.7] years; 1481 [49.0%] female; 1046 [44.8%] APOE ε4 carriers; 824 [27.3%] had depressive symptoms; 1668 [55.8%] had amyloid pathology), the presence of depressive symptoms was associated with a lower likelihood of amyloid pathology (OR, 0.73; 95% CI 0.61-0.89; P = .001). When considering subgroup effects, in individuals with NC, the presence of depressive symptoms was associated with a higher frequency of amyloid pathology in APOE ε4 noncarriers (mean difference, 5.0%; 95% CI 1.0-9.0; P = .02) but not in APOE ε4 carriers. This was not the case in individuals with MCI.</p><p><strong>Conclusions and relevance: </strong>Depressive symptoms were not consistently associated with a higher frequency of amyloid pathology in participants with NC and were associated with a lower likelihood of amyloid pathology in participants with MCI. These findings were not influenced by age, sex, or education level. Mechanisms other than amyloid accumula","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":""},"PeriodicalIF":22.5,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005786","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 : 2025-01-15DOI: 10.1001/jamapsychiatry.2024.4318
Michael Liu, Vishal R Patel, Sahil Sandhu, Rishi K Wadhera, Alex S Keuroghlian
<p><strong>Importance: </strong>In the 2020 Bostock v Clayton County decision, the US Supreme Court extended employment nondiscrimination protection to sexual minority adults. The health impacts of this ruling and similar policies related to sexual orientation-based discrimination are not currently known.</p><p><strong>Objective: </strong>To estimate changes in mental health following the Bostock decision among sexual minority adults in states that gained employment nondiscrimination protection (intervention states) compared with those in states with protections already in place (control states).</p><p><strong>Design, setting, and participants: </strong>This cross-sectional study used 2018-2022 data from the Behavioral Risk Factor Surveillance System and a difference-in-differences approach to evaluate changes in mental health after the Bostock decision by comparing sexual minority adults (aged ≥18 years and identifying as lesbian, gay, or bisexual) in 12 intervention states with those residing in 9 control states. Models were estimated for all participants and separately for employed participants. Data were analyzed between February and September 2024.</p><p><strong>Exposure: </strong>Residing in a state that gained employment nondiscrimination protection after the Bostock decision.</p><p><strong>Main outcomes and measures: </strong>The primary outcome was number of poor mental health days during the past 30 days, and the secondary outcome was severe mental distress (defined as 14 or more past-month poor mental health days).</p><p><strong>Results: </strong>Of 597 462 participants (306 365 in intervention states [77.7% aged 18-64 years and 22.3% aged ≥65 years; 51.7% female] and 291 097 in control states [77.5% aged 18-64 years and 22.5% aged ≥65 years; 50.6% female]), 5.1% in intervention states and 6.0% in control states self-identified as sexual minority adults. The mean (SE) number of past-month poor mental health days was unchanged after the Bostock decision among sexual minority adults in both intervention (from 8.70 [0.27] to 9.59 [0.24] days; adjusted difference, 0.57 [95% CI, -1.02 to 2.16] days) and control (from 8.53 [0.21] to 10.15 [0.20] days; adjusted difference, 1.17 [95% CI, -0.46 to 2.79] days) states, resulting in no differential change between the 2 groups (difference-in-differences, -0.60 days; 95% CI, -1.25 to 0.06 days). Among the subset of employed sexual minority adults, the mean (SE) number of poor mental health days did not change in intervention states (from 7.99 [0.38] to 8.83 [0.30] days; adjusted difference, 0.87 [95% CI, -0.49 to 2.22] days) but increased in control states (from 7.75 [0.27] to 9.75 [0.26] days; adjusted difference, 1.84 [95% CI, 0.44-3.24] days). These findings corresponded to a significant relative reduction in poor mental health days among employed sexual minority adults in intervention vs control states (difference-in-differences, -0.97 days; 95% CI, -1.74 to -0.21 days). Mean (SE) rates of sever
{"title":"Employment Nondiscrimination Protection and Mental Health Among Sexual Minority Adults.","authors":"Michael Liu, Vishal R Patel, Sahil Sandhu, Rishi K Wadhera, Alex S Keuroghlian","doi":"10.1001/jamapsychiatry.2024.4318","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.4318","url":null,"abstract":"<p><strong>Importance: </strong>In the 2020 Bostock v Clayton County decision, the US Supreme Court extended employment nondiscrimination protection to sexual minority adults. The health impacts of this ruling and similar policies related to sexual orientation-based discrimination are not currently known.</p><p><strong>Objective: </strong>To estimate changes in mental health following the Bostock decision among sexual minority adults in states that gained employment nondiscrimination protection (intervention states) compared with those in states with protections already in place (control states).</p><p><strong>Design, setting, and participants: </strong>This cross-sectional study used 2018-2022 data from the Behavioral Risk Factor Surveillance System and a difference-in-differences approach to evaluate changes in mental health after the Bostock decision by comparing sexual minority adults (aged ≥18 years and identifying as lesbian, gay, or bisexual) in 12 intervention states with those residing in 9 control states. Models were estimated for all participants and separately for employed participants. Data were analyzed between February and September 2024.</p><p><strong>Exposure: </strong>Residing in a state that gained employment nondiscrimination protection after the Bostock decision.</p><p><strong>Main outcomes and measures: </strong>The primary outcome was number of poor mental health days during the past 30 days, and the secondary outcome was severe mental distress (defined as 14 or more past-month poor mental health days).</p><p><strong>Results: </strong>Of 597 462 participants (306 365 in intervention states [77.7% aged 18-64 years and 22.3% aged ≥65 years; 51.7% female] and 291 097 in control states [77.5% aged 18-64 years and 22.5% aged ≥65 years; 50.6% female]), 5.1% in intervention states and 6.0% in control states self-identified as sexual minority adults. The mean (SE) number of past-month poor mental health days was unchanged after the Bostock decision among sexual minority adults in both intervention (from 8.70 [0.27] to 9.59 [0.24] days; adjusted difference, 0.57 [95% CI, -1.02 to 2.16] days) and control (from 8.53 [0.21] to 10.15 [0.20] days; adjusted difference, 1.17 [95% CI, -0.46 to 2.79] days) states, resulting in no differential change between the 2 groups (difference-in-differences, -0.60 days; 95% CI, -1.25 to 0.06 days). Among the subset of employed sexual minority adults, the mean (SE) number of poor mental health days did not change in intervention states (from 7.99 [0.38] to 8.83 [0.30] days; adjusted difference, 0.87 [95% CI, -0.49 to 2.22] days) but increased in control states (from 7.75 [0.27] to 9.75 [0.26] days; adjusted difference, 1.84 [95% CI, 0.44-3.24] days). These findings corresponded to a significant relative reduction in poor mental health days among employed sexual minority adults in intervention vs control states (difference-in-differences, -0.97 days; 95% CI, -1.74 to -0.21 days). Mean (SE) rates of sever","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":""},"PeriodicalIF":22.5,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983583","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 : 2025-01-08DOI: 10.1001/jamapsychiatry.2024.4312
Michelle Matvey, D. Parker Kelley, Ellen R. Bradley, Winston Chiong, Aoife O’Donovan, Josh Woolley
ImportanceThere is unprecedented clinician, industry, and patient interest in the therapeutic development of psychedelic drugs. This is due to a combination of promising clinical trial results, positive media coverage, and the lack of novel pharmacologic treatments for psychiatric disorders in recent decades. However, the field faces a key methodological challenge: masking participants to treatment conditions in psychedelic clinical trials has been largely unsuccessful.ObjectiveWhen participants can tell whether they received active drug or placebo, their responses to clinical assessments, questionnaires, and even their functional imaging and biological data can be influenced by preconceptions about treatment effects. Positive patient expectancies combined with ineffective masking may skew outcomes and inflate effect sizes. This complicates efforts to determine the safety and efficacy of psychedelic drugs. Here, we explore a method to help address this problem: modifying informed consent to obscure information about the study design.Evidence ReviewWe reviewed all contemporary (2000-2024) clinical trials of psychedelic or methylenedioxymethamphetamine (MDMA) therapy and corresponded with the investigators to compile information on the use of modifications to informed consent in these studies.FindingsModifying informed consent to obscure details of the study design has been implemented in several psychedelic clinical trials and may offer a way to strengthen masking. However, this approach poses significant ethical risks. We examine examples of modifications used in the psychedelic literature, discuss the current regulatory landscape, and suggest strategies to mitigate risks associated with modified informed consent.Conclusions and RelevanceIncorporating modified informed consent in future psychedelic clinical trials may improve interpretability and impact, but this has not been explicitly tested. Modifications to informed consent may not be appropriate in all cases, and risks to participants should be minimized by implementing appropriate guardrails.
{"title":"Modifying Informed Consent to Help Address Functional Unmasking in Psychedelic Clinical Trials","authors":"Michelle Matvey, D. Parker Kelley, Ellen R. Bradley, Winston Chiong, Aoife O’Donovan, Josh Woolley","doi":"10.1001/jamapsychiatry.2024.4312","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.4312","url":null,"abstract":"ImportanceThere is unprecedented clinician, industry, and patient interest in the therapeutic development of psychedelic drugs. This is due to a combination of promising clinical trial results, positive media coverage, and the lack of novel pharmacologic treatments for psychiatric disorders in recent decades. However, the field faces a key methodological challenge: masking participants to treatment conditions in psychedelic clinical trials has been largely unsuccessful.ObjectiveWhen participants can tell whether they received active drug or placebo, their responses to clinical assessments, questionnaires, and even their functional imaging and biological data can be influenced by preconceptions about treatment effects. Positive patient expectancies combined with ineffective masking may skew outcomes and inflate effect sizes. This complicates efforts to determine the safety and efficacy of psychedelic drugs. Here, we explore a method to help address this problem: modifying informed consent to obscure information about the study design.Evidence ReviewWe reviewed all contemporary (2000-2024) clinical trials of psychedelic or methylenedioxymethamphetamine (MDMA) therapy and corresponded with the investigators to compile information on the use of modifications to informed consent in these studies.FindingsModifying informed consent to obscure details of the study design has been implemented in several psychedelic clinical trials and may offer a way to strengthen masking. However, this approach poses significant ethical risks. We examine examples of modifications used in the psychedelic literature, discuss the current regulatory landscape, and suggest strategies to mitigate risks associated with modified informed consent.Conclusions and RelevanceIncorporating modified informed consent in future psychedelic clinical trials may improve interpretability and impact, but this has not been explicitly tested. Modifications to informed consent may not be appropriate in all cases, and risks to participants should be minimized by implementing appropriate guardrails.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"82 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936339","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 : 2025-01-08DOI: 10.1001/jamapsychiatry.2024.4230
Emanuel Boudriot, Marius Stephan, Finn Rabe, Lukasz Smigielski, Andrea Schmitt, Peter Falkai, Michael J. Ziller, Moritz J. Rossner, Philipp Homan, Sergi Papiol, Florian J. Raabe
ImportanceAs an accessible part of the central nervous system, the retina provides a unique window to study pathophysiological mechanisms of brain disorders in humans. Imaging and electrophysiological studies have revealed retinal alterations across several neuropsychiatric and neurological disorders, but it remains largely unclear which specific cell types and biological mechanisms are involved.ObjectiveTo determine whether specific retinal cell types are affected by genomic risk for neuropsychiatric and neurological disorders and to explore the mechanisms through which genomic risk converges in these cell types.Design, Setting, and ParticipantsThis genetic association study combined findings from genome-wide association studies in schizophrenia, bipolar disorder, major depressive disorder, multiple sclerosis, Parkinson disease, Alzheimer disease, and stroke with retinal single-cell transcriptomic datasets from humans, macaques, and mice. To identify susceptible cell types, Multi-Marker Analysis of Genomic Annotation (MAGMA) cell-type enrichment analyses were applied and subsequent pathway analyses performed. The cellular top hits were translated to the structural level using retinal optical coherence tomography (acquired between 2009 and 2010) and genotyping data in the large population-based UK Biobank cohort study. Data analysis was conducted between 2022 and 2024.Main Outcomes and MeasuresCell type–specific enrichment of genetic risk loading for neuropsychiatric and neurological disorder traits in the gene expression profiles of retinal cells.ResultsExpression profiles of amacrine cells (interneurons within the retina) were robustly enriched in schizophrenia genetic risk across mammalian species and in different developmental stages. This enrichment was primarily driven by genes involved in synapse biology. Moreover, expression profiles of retinal immune cell populations were enriched in multiple sclerosis genetic risk. No consistent cell-type associations were found for bipolar disorder, major depressive disorder, Parkinson disease, Alzheimer disease, or stroke. On the structural level, higher polygenic risk for schizophrenia was associated with thinning of the ganglion cell inner plexiform layer, which contains dendrites and synaptic connections of amacrine cells (B, −0.09; 95% CI, −0.16 to −0.03; P = .007; n = 36 349; mean [SD] age, 57.50 [8.00] years; 19 859 female [54.63%]). Higher polygenic risk for multiple sclerosis was associated with increased thickness of the retinal nerve fiber layer (B, 0.06; 95% CI, 0.02 to 0.10; P = .007; n = 36 371; mean [SD] age, 57.51 [8.00] years; 19 843 female [54.56%]).Conclusions and RelevanceThis study provides novel insights into the cellular underpinnings of retinal alterations in neuropsychiatric and neurological disorders and highlights the retina as a potential proxy to study synaptic pathology in schizophrenia.
{"title":"Genetic Analysis of Retinal Cell Types in Neuropsychiatric Disorders","authors":"Emanuel Boudriot, Marius Stephan, Finn Rabe, Lukasz Smigielski, Andrea Schmitt, Peter Falkai, Michael J. Ziller, Moritz J. Rossner, Philipp Homan, Sergi Papiol, Florian J. Raabe","doi":"10.1001/jamapsychiatry.2024.4230","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.4230","url":null,"abstract":"ImportanceAs an accessible part of the central nervous system, the retina provides a unique window to study pathophysiological mechanisms of brain disorders in humans. Imaging and electrophysiological studies have revealed retinal alterations across several neuropsychiatric and neurological disorders, but it remains largely unclear which specific cell types and biological mechanisms are involved.ObjectiveTo determine whether specific retinal cell types are affected by genomic risk for neuropsychiatric and neurological disorders and to explore the mechanisms through which genomic risk converges in these cell types.Design, Setting, and ParticipantsThis genetic association study combined findings from genome-wide association studies in schizophrenia, bipolar disorder, major depressive disorder, multiple sclerosis, Parkinson disease, Alzheimer disease, and stroke with retinal single-cell transcriptomic datasets from humans, macaques, and mice. To identify susceptible cell types, Multi-Marker Analysis of Genomic Annotation (MAGMA) cell-type enrichment analyses were applied and subsequent pathway analyses performed. The cellular top hits were translated to the structural level using retinal optical coherence tomography (acquired between 2009 and 2010) and genotyping data in the large population-based UK Biobank cohort study. Data analysis was conducted between 2022 and 2024.Main Outcomes and MeasuresCell type–specific enrichment of genetic risk loading for neuropsychiatric and neurological disorder traits in the gene expression profiles of retinal cells.ResultsExpression profiles of amacrine cells (interneurons within the retina) were robustly enriched in schizophrenia genetic risk across mammalian species and in different developmental stages. This enrichment was primarily driven by genes involved in synapse biology. Moreover, expression profiles of retinal immune cell populations were enriched in multiple sclerosis genetic risk. No consistent cell-type associations were found for bipolar disorder, major depressive disorder, Parkinson disease, Alzheimer disease, or stroke. On the structural level, higher polygenic risk for schizophrenia was associated with thinning of the ganglion cell inner plexiform layer, which contains dendrites and synaptic connections of amacrine cells (B, −0.09; 95% CI, −0.16 to −0.03; <jats:italic>P</jats:italic> = .007; n = 36 349; mean [SD] age, 57.50 [8.00] years; 19 859 female [54.63%]). Higher polygenic risk for multiple sclerosis was associated with increased thickness of the retinal nerve fiber layer (B, 0.06; 95% CI, 0.02 to 0.10; <jats:italic>P</jats:italic> = .007; n = 36 371; mean [SD] age, 57.51 [8.00] years; 19 843 female [54.56%]).Conclusions and RelevanceThis study provides novel insights into the cellular underpinnings of retinal alterations in neuropsychiatric and neurological disorders and highlights the retina as a potential proxy to study synaptic pathology in schizophrenia.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"56 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936193","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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