Pub Date : 2024-11-20DOI: 10.1001/jamapsychiatry.2024.3596
Ruth S Shim, Margarita Alegría
{"title":"Ending Unequal Treatment for People With Behavioral Health Conditions.","authors":"Ruth S Shim, Margarita Alegría","doi":"10.1001/jamapsychiatry.2024.3596","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.3596","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":""},"PeriodicalIF":22.5,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675868","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 : 2024-11-20DOI: 10.1001/jamapsychiatry.2024.3714
Demelza Smeeth, Simone Ecker, Olga Chervova, Fiona McEwen, Elie Karam, Stephan Beck, Michael Pluess
Importance: Exposure to war is associated with poor mental health outcomes. Adverse and traumatic experiences can lead to long-lasting DNA methylation changes, potentially mediating the link between adversity and mental health. To date, limited studies have investigated the impact of war on DNA methylation in children or adolescents, hampering our understanding of the biological impact of war exposure.
Objective: To identify salivary DNA methylation differences associated with war exposure in refugee children and adolescents.
Design, setting, and participants: This cohort study included Syrian refugee children and adolescents, and their primary caregiver were recruited from tented settlements in Lebanon. Data collection was carried out in 2 waves, 1 year apart, from October 2017 to January 2018 and October 2018 to January 2019. Children and their caregiver were interviewed, and children provided saliva samples for DNA extraction. Data analysis was conducted in 2022, 2023, and 2024.
Exposure: War exposure assessed by interviewing children and their caregiver using the War Events Questionnaire.
Main outcomes and measures: Salivary DNA methylation levels were assayed with the Infinium MethylationEPIC BeadChip (Illumina). Epigenetic aging acceleration was estimated using a set of preexisting epigenetic aging clocks. A literature search was conducted to identify previously reported DNA methylation correlates of childhood trauma.
Results: The study population included 1507 children and adolescents (mean [SD] age, 11.3 [2.4] years; age range, 6-19 years; 793 female [52.6%]). A total of 1449 children provided saliva samples for DNA extraction in year 1, and 872 children provided samples in year 2. Children who reported war events had a number of differentially methylated sites and regions. Enrichment analyses indicated an enrichment of gene sets associated with transmembrane transport, neurotransmission, and intracellular movement in genes that exhibited differential methylation. Sex-stratified analyses found a number of sex-specific DNA methylation differences associated with war exposure. Only 2 of 258 (0.8%) previously reported trauma-associated DNA methylation sites were associated with war exposure (B = -0.004; 95% CI, -0.005 to -0.003; Bonferroni P = .04 and B = -0.005; 95% CI, -0.006 to -0.004; Bonferroni P = .03). Any war exposure or bombardment was nominally associated with decreased epigenetic age using the Horvath multitissue clock (B = -0.39; 95% CI, -0.63 to -0.14; P = .007 and B = -0.42; 95% CI, -0.73 to -0.11; P = .002).
Conclusions and relevance: In this cohort of Syrian refugee children and adolescents, war exposure was associated with a small number of distinct differences in salivary DNA methylation.
重要性：战争暴露与不良的心理健康结果有关。逆境和创伤经历会导致 DNA 甲基化发生长期变化，从而有可能介导逆境与心理健康之间的联系。迄今为止，有关战争对儿童或青少年 DNA 甲基化影响的研究还很有限，这妨碍了我们对战争暴露的生物影响的了解：目的：确定难民儿童和青少年唾液 DNA 甲基化与战争暴露相关的差异：这项队列研究包括从黎巴嫩帐篷定居点招募的叙利亚难民儿童和青少年及其主要照顾者。数据收集分两次进行，每次相隔一年，时间分别为 2017 年 10 月至 2018 年 1 月和 2018 年 10 月至 2019 年 1 月。对儿童及其照顾者进行了访谈，儿童提供了唾液样本以提取 DNA。数据分析于 2022 年、2023 年和 2024 年进行。暴露：通过使用战争事件问卷访问儿童及其照顾者来评估战争暴露：唾液 DNA 甲基化水平通过 Infinium MethylationEPIC BeadChip（Illumina）进行检测。利用一组已有的表观遗传衰老时钟估算表观遗传衰老加速度。研究人员还进行了文献检索，以确定以前报道过的与儿童创伤相关的 DNA 甲基化因素：研究对象包括 1507 名儿童和青少年（平均 [SD] 年龄为 11.3 [2.4] 岁；年龄范围为 6-19 岁；793 名女性 [52.6%]）。共有 1449 名儿童在第一年提供了用于提取 DNA 的唾液样本，872 名儿童在第二年提供了样本。报告战争事件的儿童有许多不同的甲基化位点和区域。富集分析表明，与跨膜转运、神经传递和细胞内运动相关的基因集富集在出现差异甲基化的基因中。性别分层分析发现了一些与战争暴露有关的性别特异性 DNA 甲基化差异。之前报道的 258 个创伤相关 DNA 甲基化位点中，只有 2 个（0.8%）与战争暴露有关（B = -0.004；95% CI，-0.005 至 -0.003；Bonferroni P = .04 和 B = -0.005；95% CI，-0.006 至 -0.004；Bonferroni P = .03）。使用Horvath多组织时钟，任何战争暴露或轰炸都与表观遗传年龄的降低有名义上的联系（B = -0.39; 95% CI, -0.63 to -0.14; P = .007 and B = -0.42; 95% CI, -0.73 to -0.11; P = .002）：在这批叙利亚难民儿童和青少年中，战争暴露与唾液 DNA 甲基化的少量明显差异有关。
{"title":"War Exposure and DNA Methylation in Syrian Refugee Children and Adolescents.","authors":"Demelza Smeeth, Simone Ecker, Olga Chervova, Fiona McEwen, Elie Karam, Stephan Beck, Michael Pluess","doi":"10.1001/jamapsychiatry.2024.3714","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.3714","url":null,"abstract":"<p><strong>Importance: </strong>Exposure to war is associated with poor mental health outcomes. Adverse and traumatic experiences can lead to long-lasting DNA methylation changes, potentially mediating the link between adversity and mental health. To date, limited studies have investigated the impact of war on DNA methylation in children or adolescents, hampering our understanding of the biological impact of war exposure.</p><p><strong>Objective: </strong>To identify salivary DNA methylation differences associated with war exposure in refugee children and adolescents.</p><p><strong>Design, setting, and participants: </strong>This cohort study included Syrian refugee children and adolescents, and their primary caregiver were recruited from tented settlements in Lebanon. Data collection was carried out in 2 waves, 1 year apart, from October 2017 to January 2018 and October 2018 to January 2019. Children and their caregiver were interviewed, and children provided saliva samples for DNA extraction. Data analysis was conducted in 2022, 2023, and 2024.</p><p><strong>Exposure: </strong>War exposure assessed by interviewing children and their caregiver using the War Events Questionnaire.</p><p><strong>Main outcomes and measures: </strong>Salivary DNA methylation levels were assayed with the Infinium MethylationEPIC BeadChip (Illumina). Epigenetic aging acceleration was estimated using a set of preexisting epigenetic aging clocks. A literature search was conducted to identify previously reported DNA methylation correlates of childhood trauma.</p><p><strong>Results: </strong>The study population included 1507 children and adolescents (mean [SD] age, 11.3 [2.4] years; age range, 6-19 years; 793 female [52.6%]). A total of 1449 children provided saliva samples for DNA extraction in year 1, and 872 children provided samples in year 2. Children who reported war events had a number of differentially methylated sites and regions. Enrichment analyses indicated an enrichment of gene sets associated with transmembrane transport, neurotransmission, and intracellular movement in genes that exhibited differential methylation. Sex-stratified analyses found a number of sex-specific DNA methylation differences associated with war exposure. Only 2 of 258 (0.8%) previously reported trauma-associated DNA methylation sites were associated with war exposure (B = -0.004; 95% CI, -0.005 to -0.003; Bonferroni P = .04 and B = -0.005; 95% CI, -0.006 to -0.004; Bonferroni P = .03). Any war exposure or bombardment was nominally associated with decreased epigenetic age using the Horvath multitissue clock (B = -0.39; 95% CI, -0.63 to -0.14; P = .007 and B = -0.42; 95% CI, -0.73 to -0.11; P = .002).</p><p><strong>Conclusions and relevance: </strong>In this cohort of Syrian refugee children and adolescents, war exposure was associated with a small number of distinct differences in salivary DNA methylation.</p>","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":""},"PeriodicalIF":22.5,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675870","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 : 2024-11-20DOI: 10.1001/jamapsychiatry.2024.4051
{"title":"Error in Results and Figure.","authors":"","doi":"10.1001/jamapsychiatry.2024.4051","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.4051","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":""},"PeriodicalIF":22.5,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675869","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 : 2024-11-13DOI: 10.1001/jamapsychiatry.2024.3409
Rita Rosner, Jörn Rau, Anette Kersting, Winfried Rief, Regina Steil, Anna-Maria Rummel, Anna Vogel, Hannah Comtesse
ImportanceProlonged grief disorder (PGD) is included as a new diagnosis in international classification systems. Treatments following a cognitive behavioral model are most effective, but comparisons with active control treatments are scarce.ObjectiveTo examine whether integrative cognitive behavioral therapy for prolonged grief (PG-CBT) is superior to present-centered therapy (PCT).Design, Setting, and ParticipantsThis was a rater-blinded, multicenter, randomized clinical trial (stratified by center and relationship to the deceased) with enrollment from April 2017 to May 2022. The setting included 4 university outpatient clinics in Germany. Eligible participants were aged 18 to 75 years and had PGD based on the Prolonged Grief Disorder 13 (PG-13) interview. Participants were randomized 1:1 to PG-CBT and PCT.InterventionsPG-CBT focused on the exposure to the worst moment of the loss and cognitive restructuring of grief-related cognitions in combination with solution-focused and experiential methods (eg, walk to the grave exercise). PCT was adapted in session length and number to PG-CBT and focused on a supportive relationship and coping with daily problems that may have arisen from the loss or grief symptoms.Main Outcomes and MeasuresAll outcomes were assessed at baseline, after treatment, and 12 months after randomization at follow-up. The primary outcome was a blinded assessment of the PG-13 severity score at follow-up. Secondary outcomes were self-reported depressive, somatic, and overall psychopathological symptoms.ResultsOf 544 treatment-seeking individuals experiencing bereavement, 212 eligible participants (mean [SD] age, 51.8 [13.3] years; 173 female [82%]) with PGD based on the PG-13 interview were randomized to PG-CBT and PCT (n = 106 in each condition). In the intention-to-treat analysis, both treatments yielded high reductions in PGD severity at follow-up (PG-CBT: Cohen <jats:italic>d</jats:italic> = 1.64; 95% CI, 1.31-1.97; PCT: Cohen <jats:italic>d</jats:italic> = 1.38; 95% CI, 1.09-1.66). After treatment, participants receiving PG-CBT demonstrated significantly greater reductions in PGD severity than those receiving PCT (Cohen <jats:italic>d</jats:italic> = 0.31; 95% CI, 0.03-0.57). At follow-up, this effect was only visible on a trend level (Cohen <jats:italic>d</jats:italic> = 0.28; 95% CI, −0.02 to 0.57), whereas participants in the PG-CBT group had significantly less depressive and general psychopathological symptoms. Twenty-three participants (20%) discontinued PG-CBT treatment, and 17 participants (16%) discontinued PCT.Conclusion and RelevanceThis randomized clinical trial demonstrates that PG-CBT was superior to PCT after treatment and at follow-up with regard to comorbid symptoms. Both treatments were shown to be effective and acceptable, showing the potential for dissemination and increasing patient choice.Trial registrationGerman Clinical Trials Register (DRKS) identifier: <jats:ext-link xmlns:xlink="http://www.w3.org/199
{"title":"Grief-Specific Cognitive Behavioral Therapy vs Present-Centered Therapy","authors":"Rita Rosner, Jörn Rau, Anette Kersting, Winfried Rief, Regina Steil, Anna-Maria Rummel, Anna Vogel, Hannah Comtesse","doi":"10.1001/jamapsychiatry.2024.3409","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.3409","url":null,"abstract":"ImportanceProlonged grief disorder (PGD) is included as a new diagnosis in international classification systems. Treatments following a cognitive behavioral model are most effective, but comparisons with active control treatments are scarce.ObjectiveTo examine whether integrative cognitive behavioral therapy for prolonged grief (PG-CBT) is superior to present-centered therapy (PCT).Design, Setting, and ParticipantsThis was a rater-blinded, multicenter, randomized clinical trial (stratified by center and relationship to the deceased) with enrollment from April 2017 to May 2022. The setting included 4 university outpatient clinics in Germany. Eligible participants were aged 18 to 75 years and had PGD based on the Prolonged Grief Disorder 13 (PG-13) interview. Participants were randomized 1:1 to PG-CBT and PCT.InterventionsPG-CBT focused on the exposure to the worst moment of the loss and cognitive restructuring of grief-related cognitions in combination with solution-focused and experiential methods (eg, walk to the grave exercise). PCT was adapted in session length and number to PG-CBT and focused on a supportive relationship and coping with daily problems that may have arisen from the loss or grief symptoms.Main Outcomes and MeasuresAll outcomes were assessed at baseline, after treatment, and 12 months after randomization at follow-up. The primary outcome was a blinded assessment of the PG-13 severity score at follow-up. Secondary outcomes were self-reported depressive, somatic, and overall psychopathological symptoms.ResultsOf 544 treatment-seeking individuals experiencing bereavement, 212 eligible participants (mean [SD] age, 51.8 [13.3] years; 173 female [82%]) with PGD based on the PG-13 interview were randomized to PG-CBT and PCT (n = 106 in each condition). In the intention-to-treat analysis, both treatments yielded high reductions in PGD severity at follow-up (PG-CBT: Cohen <jats:italic>d</jats:italic> = 1.64; 95% CI, 1.31-1.97; PCT: Cohen <jats:italic>d</jats:italic> = 1.38; 95% CI, 1.09-1.66). After treatment, participants receiving PG-CBT demonstrated significantly greater reductions in PGD severity than those receiving PCT (Cohen <jats:italic>d</jats:italic> = 0.31; 95% CI, 0.03-0.57). At follow-up, this effect was only visible on a trend level (Cohen <jats:italic>d</jats:italic> = 0.28; 95% CI, −0.02 to 0.57), whereas participants in the PG-CBT group had significantly less depressive and general psychopathological symptoms. Twenty-three participants (20%) discontinued PG-CBT treatment, and 17 participants (16%) discontinued PCT.Conclusion and RelevanceThis randomized clinical trial demonstrates that PG-CBT was superior to PCT after treatment and at follow-up with regard to comorbid symptoms. Both treatments were shown to be effective and acceptable, showing the potential for dissemination and increasing patient choice.Trial registrationGerman Clinical Trials Register (DRKS) identifier: <jats:ext-link xmlns:xlink=\"http://www.w3.org/199","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"22 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610551","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 : 2024-11-13DOI: 10.1001/jamapsychiatry.2024.3532
Daniel T. Myran, Michael Pugliese, Jennifer Xiao, Tyler S. Kaster, M. Ishrat Husain, Kelly K. Anderson, Nicholas Fabiano, Stanley Wong, Jess G. Fiedorowicz, Colleen Webber, Peter Tanuseputro, Marco Solmi
ImportanceInterest in and use of hallucinogens has been increasing rapidly. While a frequently raised concern is that hallucinogens may be associated with an increased risk of psychosis, there are limited data on this association.ObjectivesTo examine whether individuals with an emergency department (ED) visit involving hallucinogen use have an increased risk of developing a schizophrenia spectrum disorder (SSD).Design, Settings, and ParticipantsThis population-based, retrospective cohort study (January 2008 to December 2021) included all individuals aged 14 to 65 years in Ontario, Canada, with no history of psychosis (SSD or substance induced). Data were analyzed from May to August 2024.ExposureAn incident ED visit involving hallucinogen use.Main Outcomes and MeasuresDiagnosis of SSD using a medical record–validated algorithm. Associations between ED visits involving hallucinogens and SSD were estimated using cause-specific adjusted hazard models. Individuals with an incident ED visit involving hallucinogens were compared with members of the general population (primary analysis) or individuals with ED visits involving alcohol or cannabis (secondary analysis).ResultsThe study included 9 244 292 individuals (mean [SD] age, 40.4 [14.7] years; 50.2% female) without a history of psychosis, with a median follow-up of 5.1 years (IQR, 2.3-8.6 years); 5217 (0.1%) had an incident ED visit involving hallucinogen use. Annual rates of incident ED visits involving hallucinogens were stable between 2008 and 2012 and then increased by 86.4% between 2013 and 2021 (3.4 vs 6.4 per 100 000 individuals). Individuals with ED visits involving hallucinogens had a greater risk of being diagnosed with an SSD within 3 years compared with the general population (age- and sex-adjusted hazard ratio [HR], 21.32 [95% CI, 18.58-24.47]; absolute proportion with SSD at 3 years, 208 of 5217 with hallucinogen use [3.99%] vs 13 639 of 9 239 075 in the general population [0.15%]). After adjustment for comorbid substance use and mental health conditions, individuals with hallucinogen ED visits had a greater risk of SSD compared with the general population (HR, 3.53; 95% CI, 3.05-4.09). Emergency department visits involving hallucinogens were associated with an increased risk of SSD within 3 years compared with ED visits involving alcohol (HR, 4.66; 95% CI, 3.82-5.68) and cannabis (HR, 1.47; 95% CI, 1.21-1.80) in the fully adjusted model.Conclusions and RelevanceIn this cohort study, individuals with an ED visit involving hallucinogen use had a greater risk of developing an SSD compared with both the general population and with individuals with ED visits for other types of substances. These findings have important clinical and policy implications given the increasing use of hallucinogens and associated ED visits.
{"title":"Emergency Department Visits Involving Hallucinogen Use and Risk of Schizophrenia Spectrum Disorder","authors":"Daniel T. Myran, Michael Pugliese, Jennifer Xiao, Tyler S. Kaster, M. Ishrat Husain, Kelly K. Anderson, Nicholas Fabiano, Stanley Wong, Jess G. Fiedorowicz, Colleen Webber, Peter Tanuseputro, Marco Solmi","doi":"10.1001/jamapsychiatry.2024.3532","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.3532","url":null,"abstract":"ImportanceInterest in and use of hallucinogens has been increasing rapidly. While a frequently raised concern is that hallucinogens may be associated with an increased risk of psychosis, there are limited data on this association.ObjectivesTo examine whether individuals with an emergency department (ED) visit involving hallucinogen use have an increased risk of developing a schizophrenia spectrum disorder (SSD).Design, Settings, and ParticipantsThis population-based, retrospective cohort study (January 2008 to December 2021) included all individuals aged 14 to 65 years in Ontario, Canada, with no history of psychosis (SSD or substance induced). Data were analyzed from May to August 2024.ExposureAn incident ED visit involving hallucinogen use.Main Outcomes and MeasuresDiagnosis of SSD using a medical record–validated algorithm. Associations between ED visits involving hallucinogens and SSD were estimated using cause-specific adjusted hazard models. Individuals with an incident ED visit involving hallucinogens were compared with members of the general population (primary analysis) or individuals with ED visits involving alcohol or cannabis (secondary analysis).ResultsThe study included 9 244 292 individuals (mean [SD] age, 40.4 [14.7] years; 50.2% female) without a history of psychosis, with a median follow-up of 5.1 years (IQR, 2.3-8.6 years); 5217 (0.1%) had an incident ED visit involving hallucinogen use. Annual rates of incident ED visits involving hallucinogens were stable between 2008 and 2012 and then increased by 86.4% between 2013 and 2021 (3.4 vs 6.4 per 100 000 individuals). Individuals with ED visits involving hallucinogens had a greater risk of being diagnosed with an SSD within 3 years compared with the general population (age- and sex-adjusted hazard ratio [HR], 21.32 [95% CI, 18.58-24.47]; absolute proportion with SSD at 3 years, 208 of 5217 with hallucinogen use [3.99%] vs 13 639 of 9 239 075 in the general population [0.15%]). After adjustment for comorbid substance use and mental health conditions, individuals with hallucinogen ED visits had a greater risk of SSD compared with the general population (HR, 3.53; 95% CI, 3.05-4.09). Emergency department visits involving hallucinogens were associated with an increased risk of SSD within 3 years compared with ED visits involving alcohol (HR, 4.66; 95% CI, 3.82-5.68) and cannabis (HR, 1.47; 95% CI, 1.21-1.80) in the fully adjusted model.Conclusions and RelevanceIn this cohort study, individuals with an ED visit involving hallucinogen use had a greater risk of developing an SSD compared with both the general population and with individuals with ED visits for other types of substances. These findings have important clinical and policy implications given the increasing use of hallucinogens and associated ED visits.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"70 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610548","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 : 2024-11-13DOI: 10.1001/jamapsychiatry.2024.3599
Markku Lähteenvuo, Jari Tiihonen, Anssi Solismaa, Antti Tanskanen, Ellenor Mittendorfer-Rutz, Heidi Taipale
ImportancePreliminary studies suggest that glucagon-like peptide-1 receptor (GLP-1) agonists, used to treat type 2 diabetes and obesity, may decrease alcohol consumption.ObjectiveTo test whether the risk of hospitalization due to alcohol use disorder (AUD) is decreased during the use of GLP-1 agonists compared with periods of nonuse for the same individual.Design, Setting, and ParticipantsThis cohort study was an observational study conducted nationwide in Sweden using data from January 2006 to December 2023. The population-based cohort was identified from registers of inpatient care, specialized outpatient care, sickness absence, and disability pension. Participants were all residents aged 16 to 64 years who had a diagnosis of AUD.ExposuresThe primary exposure was use of individual GLP-1 agonists (compared with nonuse of GLP-1 agonists), and the secondary exposure was medications with indication for AUD.Main Outcomes and MeasuresThe primary outcome was AUD hospitalization analyzed in a Cox regression within-individual model. Secondary outcomes were any substance use disorder (SUD)–related hospitalization, somatic hospitalization, and suicide attempt.ResultsThe cohort included 227 866 individuals with AUD; 144 714 (63.5%) were male and 83 154 (36.5%) were female, with a mean (SD) age of 40.0 (15.7) years. Median (IQR) follow-up time was 8.8 (4.0-13.3) years. A total of 133 210 individuals (58.5%) experienced AUD hospitalization. Semaglutide (4321 users) was associated with the lowest risk (AUD: adjusted hazard ratio [aHR], 0.64; 95% CI, 0.50-0.83; any SUD: aHR, 0.68; 95% CI, 0.54-0.85) and use of liraglutide (2509 users) with the second lowest risk (AUD: aHR, 0.72; 95% CI, 0.57-0.92; any SUD: aHR, 0.78; 95% CI, 0.64-0.97) of both AUD and SUD hospitalization. Use of any AUD medication was associated with a modestly decreased risk (aHR, 0.98; 95% CI, 0.96-1.00). Semaglutide (aHR, 0.78; 95% CI, 0.68-0.90) and liraglutide (aHR, 0.79; 95% CI, 0.69-0.91) use were also associated with decreased risk of somatic hospitalizations but not associated with suicide attempts (semaglutide: aHR, 0.55; 95% CI, 0.23-1.30; liraglutide: aHR, 1.08; 95% CI, 0.55-2.15).Conclusions and RelevanceAmong patients with AUD and comorbid obesity/type 2 diabetes, the use of semaglutide and liraglutide were associated with a substantially decreased risk of hospitalization due to AUD. This risk was lower than that of officially approved AUD medications. Semaglutide and liraglutide may be effective in the treatment of AUD, and clinical trials are urgently needed to confirm these findings.
{"title":"Repurposing Semaglutide and Liraglutide for Alcohol Use Disorder","authors":"Markku Lähteenvuo, Jari Tiihonen, Anssi Solismaa, Antti Tanskanen, Ellenor Mittendorfer-Rutz, Heidi Taipale","doi":"10.1001/jamapsychiatry.2024.3599","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.3599","url":null,"abstract":"ImportancePreliminary studies suggest that glucagon-like peptide-1 receptor (GLP-1) agonists, used to treat type 2 diabetes and obesity, may decrease alcohol consumption.ObjectiveTo test whether the risk of hospitalization due to alcohol use disorder (AUD) is decreased during the use of GLP-1 agonists compared with periods of nonuse for the same individual.Design, Setting, and ParticipantsThis cohort study was an observational study conducted nationwide in Sweden using data from January 2006 to December 2023. The population-based cohort was identified from registers of inpatient care, specialized outpatient care, sickness absence, and disability pension. Participants were all residents aged 16 to 64 years who had a diagnosis of AUD.ExposuresThe primary exposure was use of individual GLP-1 agonists (compared with nonuse of GLP-1 agonists), and the secondary exposure was medications with indication for AUD.Main Outcomes and MeasuresThe primary outcome was AUD hospitalization analyzed in a Cox regression within-individual model. Secondary outcomes were any substance use disorder (SUD)–related hospitalization, somatic hospitalization, and suicide attempt.ResultsThe cohort included 227 866 individuals with AUD; 144 714 (63.5%) were male and 83 154 (36.5%) were female, with a mean (SD) age of 40.0 (15.7) years. Median (IQR) follow-up time was 8.8 (4.0-13.3) years. A total of 133 210 individuals (58.5%) experienced AUD hospitalization. Semaglutide (4321 users) was associated with the lowest risk (AUD: adjusted hazard ratio [aHR], 0.64; 95% CI, 0.50-0.83; any SUD: aHR, 0.68; 95% CI, 0.54-0.85) and use of liraglutide (2509 users) with the second lowest risk (AUD: aHR, 0.72; 95% CI, 0.57-0.92; any SUD: aHR, 0.78; 95% CI, 0.64-0.97) of both AUD and SUD hospitalization. Use of any AUD medication was associated with a modestly decreased risk (aHR, 0.98; 95% CI, 0.96-1.00). Semaglutide (aHR, 0.78; 95% CI, 0.68-0.90) and liraglutide (aHR, 0.79; 95% CI, 0.69-0.91) use were also associated with decreased risk of somatic hospitalizations but not associated with suicide attempts (semaglutide: aHR, 0.55; 95% CI, 0.23-1.30; liraglutide: aHR, 1.08; 95% CI, 0.55-2.15).Conclusions and RelevanceAmong patients with AUD and comorbid obesity/type 2 diabetes, the use of semaglutide and liraglutide were associated with a substantially decreased risk of hospitalization due to AUD. This risk was lower than that of officially approved AUD medications. Semaglutide and liraglutide may be effective in the treatment of AUD, and clinical trials are urgently needed to confirm these findings.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"11 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610134","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 : 2024-11-13DOI: 10.1001/jamapsychiatry.2024.3608
M. Belen Blasco, Kankana Nisha Aji, Christian Ramos-Jiménez, Ilana Ruth Leppert, Christine Lucas Tardif, Johan Cohen, Pablo M. Rusjan, Romina Mizrahi
ImportanceSynaptic dysfunction is involved in schizophrenia pathophysiology. However, whether in vivo synaptic density is reduced in early stages of psychosis, including its high-risk states, remains unclear.ObjectiveTo investigate whether synaptic density (synaptic vesicle glycoprotein 2A [SV2A] binding potential) is reduced in first-episode psychosis (FEP) and in clinical high risk (CHR) and investigate the effect of cannabis use on synaptic density and examine its relationship with psychotic symptoms and gray matter microstructure across groups.Design, Setting, and ParticipantsThis cross-sectional study was performed in a tertiary care psychiatric hospital from July 2021 to October 2023. Participants were patients with antipsychotic-free or minimally exposed FEP or CHR and healthy controls with a clean urine drug screen (except cannabis).Main Outcomes and MeasuresSynaptic density was quantified with dynamic 90-minute [<jats:sup>18</jats:sup>F]SynVesT-1 positron emission tomography (PET) scans across prioritized brain regions of interest (ROIs) delineated in individual magnetic resonance images (MRIs). Cannabis use was confirmed with urine drug screens. Gray matter microstructure was assessed using diffusion-weighted MRI to estimate neurite density.ResultsA total of 49 participants were included, including 16 patients with FEP (mean [SD] age, 26.1 [4.6] years; 9 males and 7 females), 17 patients at CHR (mean [SD] age, 21.2 [3.5] years; 8 males and 9 females), and 16 healthy controls (mean [SD] age, 23.4 [3.6] years; 7 males and 9 females). Synaptic density was significantly different between groups (<jats:italic>F</jats:italic><jats:sub>2,273</jats:sub> = 4.02, <jats:italic>P</jats:italic> = .02, Cohen <jats:italic>F</jats:italic> = 0.17; ROI: <jats:italic>F</jats:italic><jats:sub>5,273</jats:sub> = 360.18, <jats:italic>P</jats:italic> &lt; .01, Cohen <jats:italic>F</jats:italic> = 2.55) with a group × ROI interaction (<jats:italic>F</jats:italic><jats:sub>10,273</jats:sub> = 2.67, <jats:italic>P</jats:italic> &lt; .01, Cohen <jats:italic>F</jats:italic> = 0.32). Synaptic density was lower in cannabis users (<jats:italic>F</jats:italic><jats:sub>1,272</jats:sub> = 5.31, <jats:italic>P</jats:italic> = .02, Cohen <jats:italic>F</jats:italic> = 0.14). Lower synaptic density across groups was associated with more negative symptoms (Positive and Negative Syndrome Scale negative scores: <jats:italic>F</jats:italic><jats:sub>1,81</jats:sub> = 4.31, <jats:italic>P</jats:italic> = .04, Cohen <jats:italic>F</jats:italic> = 0.23; Scale of Psychosis-Risk Symptoms negative scores: <jats:italic>F</jats:italic><jats:sub>1,90</jats:sub> = 4.12, <jats:italic>P</jats:italic> = .04, Cohen <jats:italic>F</jats:italic> = 0.21). SV2A binding potential was significantly associated with neurite density index (<jats:italic>F</jats:italic><jats:sub>1,138</jats:sub> = 6.76, <jats:italic>P</jats:italic> = .01, Cohen <jats:italic>F</jats:italic> = 0.22).Con
{"title":"Synaptic Density in Early Stages of Psychosis and Clinical High Risk","authors":"M. Belen Blasco, Kankana Nisha Aji, Christian Ramos-Jiménez, Ilana Ruth Leppert, Christine Lucas Tardif, Johan Cohen, Pablo M. Rusjan, Romina Mizrahi","doi":"10.1001/jamapsychiatry.2024.3608","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.3608","url":null,"abstract":"ImportanceSynaptic dysfunction is involved in schizophrenia pathophysiology. However, whether in vivo synaptic density is reduced in early stages of psychosis, including its high-risk states, remains unclear.ObjectiveTo investigate whether synaptic density (synaptic vesicle glycoprotein 2A [SV2A] binding potential) is reduced in first-episode psychosis (FEP) and in clinical high risk (CHR) and investigate the effect of cannabis use on synaptic density and examine its relationship with psychotic symptoms and gray matter microstructure across groups.Design, Setting, and ParticipantsThis cross-sectional study was performed in a tertiary care psychiatric hospital from July 2021 to October 2023. Participants were patients with antipsychotic-free or minimally exposed FEP or CHR and healthy controls with a clean urine drug screen (except cannabis).Main Outcomes and MeasuresSynaptic density was quantified with dynamic 90-minute [<jats:sup>18</jats:sup>F]SynVesT-1 positron emission tomography (PET) scans across prioritized brain regions of interest (ROIs) delineated in individual magnetic resonance images (MRIs). Cannabis use was confirmed with urine drug screens. Gray matter microstructure was assessed using diffusion-weighted MRI to estimate neurite density.ResultsA total of 49 participants were included, including 16 patients with FEP (mean [SD] age, 26.1 [4.6] years; 9 males and 7 females), 17 patients at CHR (mean [SD] age, 21.2 [3.5] years; 8 males and 9 females), and 16 healthy controls (mean [SD] age, 23.4 [3.6] years; 7 males and 9 females). Synaptic density was significantly different between groups (<jats:italic>F</jats:italic><jats:sub>2,273</jats:sub> = 4.02, <jats:italic>P</jats:italic> = .02, Cohen <jats:italic>F</jats:italic> = 0.17; ROI: <jats:italic>F</jats:italic><jats:sub>5,273</jats:sub> = 360.18, <jats:italic>P</jats:italic> &amp;lt; .01, Cohen <jats:italic>F</jats:italic> = 2.55) with a group × ROI interaction (<jats:italic>F</jats:italic><jats:sub>10,273</jats:sub> = 2.67, <jats:italic>P</jats:italic> &amp;lt; .01, Cohen <jats:italic>F</jats:italic> = 0.32). Synaptic density was lower in cannabis users (<jats:italic>F</jats:italic><jats:sub>1,272</jats:sub> = 5.31, <jats:italic>P</jats:italic> = .02, Cohen <jats:italic>F</jats:italic> = 0.14). Lower synaptic density across groups was associated with more negative symptoms (Positive and Negative Syndrome Scale negative scores: <jats:italic>F</jats:italic><jats:sub>1,81</jats:sub> = 4.31, <jats:italic>P</jats:italic> = .04, Cohen <jats:italic>F</jats:italic> = 0.23; Scale of Psychosis-Risk Symptoms negative scores: <jats:italic>F</jats:italic><jats:sub>1,90</jats:sub> = 4.12, <jats:italic>P</jats:italic> = .04, Cohen <jats:italic>F</jats:italic> = 0.21). SV2A binding potential was significantly associated with neurite density index (<jats:italic>F</jats:italic><jats:sub>1,138</jats:sub> = 6.76, <jats:italic>P</jats:italic> = .01, Cohen <jats:italic>F</jats:italic> = 0.22).Con","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"44 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610141","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 : 2024-11-13DOI: 10.1001/jamapsychiatry.2024.3592
Hugo Bottemanne, Lucie Joly
{"title":"How the Paternal Brain Is Wired by Pregnancy.","authors":"Hugo Bottemanne, Lucie Joly","doi":"10.1001/jamapsychiatry.2024.3592","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.3592","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":""},"PeriodicalIF":22.5,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621064","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 : 2024-11-06DOI: 10.1001/jamapsychiatry.2024.3435
David T Zhu
{"title":"Racial and Ethnic Disparities in Fentanyl and Polysubstance Overdose Deaths.","authors":"David T Zhu","doi":"10.1001/jamapsychiatry.2024.3435","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.3435","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":""},"PeriodicalIF":22.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582773","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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