Pub Date : 2025-01-01DOI: 10.1001/jamapsychiatry.2024.3426
Allison M Lake, Yu Zhou, Bo Wang, Ky'Era V Actkins, Yingzhe Zhang, John P Shelley, Anindita Rajamani, Michael Steigman, Chris J Kennedy, Jordan W Smoller, Karmel W Choi, Nikhil K Khankari, Lea K Davis
<p><strong>Importance: </strong>Leveraging real-world clinical biobanks to investigate the associations between genetic and environmental risk factors for mental illness may help direct clinical screening efforts and evaluate the portability of polygenic scores across environmental contexts.</p><p><strong>Objective: </strong>To examine the associations between sexual trauma, polygenic liability to mental health outcomes, and clinical diagnoses of schizophrenia, bipolar disorder, and major depressive disorder in a clinical biobank setting.</p><p><strong>Design, setting, and participants: </strong>This genetic association study was conducted using clinical and genotyping data from 96 002 participants across hospital-linked biobanks located at Vanderbilt University Medical Center (VUMC), Nashville, Tennessee (including 58 262 individuals with high genetic similarity to the 1000 Genomes Project [1KG] Northern European from Utah reference population [1KG-EU-clustered] and 11 047 with high genetic similarity to the 1KG African-ancestry reference population of Yoruba in Ibadan, Nigeria [1KG-YRI-clustered]), and Mass General Brigham (MGB), Boston, Massachusetts (26 693 individuals with high genetic similarity to the combined European-ancestry superpopulation [1KG-EU-clustered]). Clinical data analyzed included diagnostic billing codes and clinical notes spanning from 1976 to 2023. Data analysis was performed from 2022 to 2024.</p><p><strong>Exposures: </strong>Clinically documented sexual trauma disclosures and polygenic scores for schizophrenia, bipolar disorder, and major depressive disorder.</p><p><strong>Main outcomes and measures: </strong>Diagnoses of schizophrenia, bipolar disorder, and major depressive disorder, determined by aggregating related diagnostic billing codes, were the dependent variables in logistic regression models including sexual trauma disclosure status, polygenic scores, and their interactions as the independent variables.</p><p><strong>Results: </strong>Across the VUMC and MGB biobanks, 96 002 individuals were included in analyses (VUMC 1KG-EU-clustered: 33 011 [56.7%] female; median [range] age, 56.8 [10.0 to >89] years; MGB 1KG-EU-clustered: 14 647 [54.9%] female; median [range] age, 58.0 [10.0 to >89] years; VUMC 1KG-YRI-clustered: 6961 [63.0%] female; median [range] age, 44.6 [10.1 to >89] years). Sexual trauma history was associated with all mental health conditions across institutions (ORs ranged from 8.83 [95% CI, 5.50-14.18] for schizophrenia in the VUMC 1KG-YRI-clustered cohort to 17.65 [95% CI, 12.77-24.40] for schizophrenia in the VUMC 1KG-EU-clustered cohort). Sexual trauma history and polygenic scores jointly explained 3.8% to 8.8% of mental health phenotypic variance. Schizophrenia and bipolar disorder polygenic scores had greater associations with mental health outcomes in individuals with no documented disclosures of sexual trauma (schizophrenia interaction: OR, 0.70 [95% CI, 0.56-0.88]; bipolar disorder interac
{"title":"Sexual Trauma, Polygenic Scores, and Mental Health Diagnoses and Outcomes.","authors":"Allison M Lake, Yu Zhou, Bo Wang, Ky'Era V Actkins, Yingzhe Zhang, John P Shelley, Anindita Rajamani, Michael Steigman, Chris J Kennedy, Jordan W Smoller, Karmel W Choi, Nikhil K Khankari, Lea K Davis","doi":"10.1001/jamapsychiatry.2024.3426","DOIUrl":"10.1001/jamapsychiatry.2024.3426","url":null,"abstract":"<p><strong>Importance: </strong>Leveraging real-world clinical biobanks to investigate the associations between genetic and environmental risk factors for mental illness may help direct clinical screening efforts and evaluate the portability of polygenic scores across environmental contexts.</p><p><strong>Objective: </strong>To examine the associations between sexual trauma, polygenic liability to mental health outcomes, and clinical diagnoses of schizophrenia, bipolar disorder, and major depressive disorder in a clinical biobank setting.</p><p><strong>Design, setting, and participants: </strong>This genetic association study was conducted using clinical and genotyping data from 96 002 participants across hospital-linked biobanks located at Vanderbilt University Medical Center (VUMC), Nashville, Tennessee (including 58 262 individuals with high genetic similarity to the 1000 Genomes Project [1KG] Northern European from Utah reference population [1KG-EU-clustered] and 11 047 with high genetic similarity to the 1KG African-ancestry reference population of Yoruba in Ibadan, Nigeria [1KG-YRI-clustered]), and Mass General Brigham (MGB), Boston, Massachusetts (26 693 individuals with high genetic similarity to the combined European-ancestry superpopulation [1KG-EU-clustered]). Clinical data analyzed included diagnostic billing codes and clinical notes spanning from 1976 to 2023. Data analysis was performed from 2022 to 2024.</p><p><strong>Exposures: </strong>Clinically documented sexual trauma disclosures and polygenic scores for schizophrenia, bipolar disorder, and major depressive disorder.</p><p><strong>Main outcomes and measures: </strong>Diagnoses of schizophrenia, bipolar disorder, and major depressive disorder, determined by aggregating related diagnostic billing codes, were the dependent variables in logistic regression models including sexual trauma disclosure status, polygenic scores, and their interactions as the independent variables.</p><p><strong>Results: </strong>Across the VUMC and MGB biobanks, 96 002 individuals were included in analyses (VUMC 1KG-EU-clustered: 33 011 [56.7%] female; median [range] age, 56.8 [10.0 to >89] years; MGB 1KG-EU-clustered: 14 647 [54.9%] female; median [range] age, 58.0 [10.0 to >89] years; VUMC 1KG-YRI-clustered: 6961 [63.0%] female; median [range] age, 44.6 [10.1 to >89] years). Sexual trauma history was associated with all mental health conditions across institutions (ORs ranged from 8.83 [95% CI, 5.50-14.18] for schizophrenia in the VUMC 1KG-YRI-clustered cohort to 17.65 [95% CI, 12.77-24.40] for schizophrenia in the VUMC 1KG-EU-clustered cohort). Sexual trauma history and polygenic scores jointly explained 3.8% to 8.8% of mental health phenotypic variance. Schizophrenia and bipolar disorder polygenic scores had greater associations with mental health outcomes in individuals with no documented disclosures of sexual trauma (schizophrenia interaction: OR, 0.70 [95% CI, 0.56-0.88]; bipolar disorder interac","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":"75-84"},"PeriodicalIF":22.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11581726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1001/jamapsychiatry.2024.2752
M Ishrat Husain, Tayyeba Kiran, Rabia Sattar, Ameer B Khoso, Ming Wai Wan, Daisy R Singla, Madeha Umer, Rabdino Mangrio, Paul Bassett, Imran B Chaudhry, Shehla N Zafar, Farhat A Jafri, Nasim Chaudhry, Nusrat Husain
<p><strong>Importance: </strong>Male postpartum depression is prevalent across populations; however, there is limited evidence on strategies to address it, particularly in low-income settings.</p><p><strong>Objective: </strong>To evaluate the effectiveness of Learning Through Play Plus Dads (LTP + Dads), a nonspecialist-delivered psychosocial intervention, in improving symptoms of male postpartum depression compared to treatment as usual.</p><p><strong>Design, setting, and participants: </strong>This cluster randomized clinical trial was conducted in Karachi, Pakistan, between June 2018 and November 2019. Assessors were blind to treatment allocation. Participants were recruited from 2 large towns in the city of Karachi via basic health units. Fathers aged 18 years and older with a DSM-5 diagnosis of major depressive episode and a child younger than 30 months were recruited. Of 1582 fathers approached, 1527 were screened and 357 were randomized in a 1:1 ratio to either the intervention or treatment as usual; 328 were included in the final analysis. Data were analyzed from April to June 2022.</p><p><strong>Interventions: </strong>LTP + Dads is a manualized intervention combining parenting skills training, play therapy, and cognitive behavior therapy. The intervention was delivered by community health workers via 12 group sessions over 4 months.</p><p><strong>Main outcomes and measures: </strong>The primary outcome was change in 17-item Hamilton Depression Rating Scale score at 4 months. Secondary outcomes included anxiety symptoms; parenting stress; intimate partner violence; functioning; quality of life; and child social, emotional, and physical health outcomes. Assessments were completed at baseline and 4 and 6 months postrandomization.</p><p><strong>Results: </strong>Of the 357 fathers included (mean [SD] age, 31.44 [7.24] years), 171 were randomized to the intervention and 186 to treatment as usual. Participants randomized to the intervention demonstrated significantly greater improvements in depression (group difference ratio [GDR], 0.66; 95% CI, 0.47 to 0.91; P < .001), anxiety (GDR, 0.62; 95% CI, 0.48 to 0.81; P < .001), parenting stress (GDR, -12.5; 95% CI, -19.1 to -6.0; P < .001), intimate partner violence (GDR, 0.89; 95% CI, 0.80 to 1.00; P = .05), disability (GDR, 0.77; 95% CI, 0.61 to 0.97; P = .03), and health-related quality of life (GDR, 12.7; 95% CI, 0.17 to 0.34; P < .001) at 4 months. The difference in depression and parenting stress was sustained at 6 months. Children of fathers randomized to the parenting intervention had significantly greater improvements in social-emotional development scores (mean difference, -20.8; 95% CI, -28.8 to -12.9; P < .001) at 6 months.</p><p><strong>Conclusions and relevance: </strong>The psychosocial parenting intervention in this study has the potential to improve paternal mental health and child development in Pakistan. Further studies in other populations and with longer follow-up are warranted
{"title":"A Group Parenting Intervention for Male Postpartum Depression: A Cluster Randomized Clinical Trial.","authors":"M Ishrat Husain, Tayyeba Kiran, Rabia Sattar, Ameer B Khoso, Ming Wai Wan, Daisy R Singla, Madeha Umer, Rabdino Mangrio, Paul Bassett, Imran B Chaudhry, Shehla N Zafar, Farhat A Jafri, Nasim Chaudhry, Nusrat Husain","doi":"10.1001/jamapsychiatry.2024.2752","DOIUrl":"10.1001/jamapsychiatry.2024.2752","url":null,"abstract":"<p><strong>Importance: </strong>Male postpartum depression is prevalent across populations; however, there is limited evidence on strategies to address it, particularly in low-income settings.</p><p><strong>Objective: </strong>To evaluate the effectiveness of Learning Through Play Plus Dads (LTP + Dads), a nonspecialist-delivered psychosocial intervention, in improving symptoms of male postpartum depression compared to treatment as usual.</p><p><strong>Design, setting, and participants: </strong>This cluster randomized clinical trial was conducted in Karachi, Pakistan, between June 2018 and November 2019. Assessors were blind to treatment allocation. Participants were recruited from 2 large towns in the city of Karachi via basic health units. Fathers aged 18 years and older with a DSM-5 diagnosis of major depressive episode and a child younger than 30 months were recruited. Of 1582 fathers approached, 1527 were screened and 357 were randomized in a 1:1 ratio to either the intervention or treatment as usual; 328 were included in the final analysis. Data were analyzed from April to June 2022.</p><p><strong>Interventions: </strong>LTP + Dads is a manualized intervention combining parenting skills training, play therapy, and cognitive behavior therapy. The intervention was delivered by community health workers via 12 group sessions over 4 months.</p><p><strong>Main outcomes and measures: </strong>The primary outcome was change in 17-item Hamilton Depression Rating Scale score at 4 months. Secondary outcomes included anxiety symptoms; parenting stress; intimate partner violence; functioning; quality of life; and child social, emotional, and physical health outcomes. Assessments were completed at baseline and 4 and 6 months postrandomization.</p><p><strong>Results: </strong>Of the 357 fathers included (mean [SD] age, 31.44 [7.24] years), 171 were randomized to the intervention and 186 to treatment as usual. Participants randomized to the intervention demonstrated significantly greater improvements in depression (group difference ratio [GDR], 0.66; 95% CI, 0.47 to 0.91; P < .001), anxiety (GDR, 0.62; 95% CI, 0.48 to 0.81; P < .001), parenting stress (GDR, -12.5; 95% CI, -19.1 to -6.0; P < .001), intimate partner violence (GDR, 0.89; 95% CI, 0.80 to 1.00; P = .05), disability (GDR, 0.77; 95% CI, 0.61 to 0.97; P = .03), and health-related quality of life (GDR, 12.7; 95% CI, 0.17 to 0.34; P < .001) at 4 months. The difference in depression and parenting stress was sustained at 6 months. Children of fathers randomized to the parenting intervention had significantly greater improvements in social-emotional development scores (mean difference, -20.8; 95% CI, -28.8 to -12.9; P < .001) at 6 months.</p><p><strong>Conclusions and relevance: </strong>The psychosocial parenting intervention in this study has the potential to improve paternal mental health and child development in Pakistan. Further studies in other populations and with longer follow-up are warranted","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":"22-30"},"PeriodicalIF":22.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1001/jamapsychiatry.2024.2871
Artur Menegaz de Almeida, Francisco Cezar Aquino de Moraes, Maria Eduarda Cavalcanti Souza, Jorge Henrique Cavalcanti Orestes Cardoso, Fernanda Tamashiro, Celso Miranda, Lilianne Fernandes, Michele Kreuz, Francinny Alves Kelly
Importance: Seasonal humor disorders are prone to have a link with daylight exposure. However, the effect of external light on nonseasonal disorders remains unclear. Evidence is lacking for the validity of bright light therapy (BLT) as an adjunctive treatment for these patients.
Objective: To assess BLT effectiveness as an adjunctive treatment for nonseasonal depressive disorders.
Data sources: In March 2024, a comprehensive search was performed of publications in the MEDLINE, Embase, and Cochrane databases for randomized clinical trials (RCTs) evaluating BLT effects in patients with nonseasonal depression.
Study selection: RCTs published since 2000 were eligible. Comparisons between BLT and dim red light or antidepressant monotherapy alone were considered for inclusion.
Data extraction and synthesis: Using the systematic review approach on RCTs published from January 1, 2000, through March 25, 2024, differences between patients treated with and without BLT were estimated using the Mantel-Haenszel method; heterogeneity was assessed using I2 statistics.
Main outcomes and measures: Remission of symptoms, response to treatment rates, and depression scales were assessed.
Results: In this systematic review and meta-analysis of 11 unique trials with data from 858 patients (649 female [75.6%]), statistically significant better remission and response rates were found in the BLT group (remission: 40.7% vs 23.5%; odds ratio [OR], 2.42; 95% CI, 1.50-3.91; P <.001; I2 = 21%; response: 60.4% vs 38.6%; OR, 2.34; 95% CI, 1.46-3.75; P <.001; I2 = 41%). With BLT, subgroup analysis based on follow-up times also showed better remission (<4 weeks: 27.4% vs 9.2%; OR, 3.59; 95% CI, 1.45-8.88; P = .005; I2 = 0% and >4 weeks: 46.6% vs 29.1%; OR, 2.18; 95% CI, 1.19-4.00; P = .01; I2 = 47%) and response (<4 weeks: 55.6% vs 27.4%; OR, 3.65; 95% CI, 1.81-7.33; P <.001; I2 = 35% and >4 weeks: 63.0% vs 44.9%; OR, 1.79; 95% CI, 1.01-3.17; P = .04; I2 = 32%) rates.
Conclusions and relevance: Results of this systematic review and meta-analysis reveal that BLT was an effective adjunctive treatment for nonseasonal depressive disorders. Additionally, results suggest that BLT may improve the response time to the initial treatment.
{"title":"Bright Light Therapy for Nonseasonal Depressive Disorders: A Systematic Review and Meta-Analysis.","authors":"Artur Menegaz de Almeida, Francisco Cezar Aquino de Moraes, Maria Eduarda Cavalcanti Souza, Jorge Henrique Cavalcanti Orestes Cardoso, Fernanda Tamashiro, Celso Miranda, Lilianne Fernandes, Michele Kreuz, Francinny Alves Kelly","doi":"10.1001/jamapsychiatry.2024.2871","DOIUrl":"10.1001/jamapsychiatry.2024.2871","url":null,"abstract":"<p><strong>Importance: </strong>Seasonal humor disorders are prone to have a link with daylight exposure. However, the effect of external light on nonseasonal disorders remains unclear. Evidence is lacking for the validity of bright light therapy (BLT) as an adjunctive treatment for these patients.</p><p><strong>Objective: </strong>To assess BLT effectiveness as an adjunctive treatment for nonseasonal depressive disorders.</p><p><strong>Data sources: </strong>In March 2024, a comprehensive search was performed of publications in the MEDLINE, Embase, and Cochrane databases for randomized clinical trials (RCTs) evaluating BLT effects in patients with nonseasonal depression.</p><p><strong>Study selection: </strong>RCTs published since 2000 were eligible. Comparisons between BLT and dim red light or antidepressant monotherapy alone were considered for inclusion.</p><p><strong>Data extraction and synthesis: </strong>Using the systematic review approach on RCTs published from January 1, 2000, through March 25, 2024, differences between patients treated with and without BLT were estimated using the Mantel-Haenszel method; heterogeneity was assessed using I2 statistics.</p><p><strong>Main outcomes and measures: </strong>Remission of symptoms, response to treatment rates, and depression scales were assessed.</p><p><strong>Results: </strong>In this systematic review and meta-analysis of 11 unique trials with data from 858 patients (649 female [75.6%]), statistically significant better remission and response rates were found in the BLT group (remission: 40.7% vs 23.5%; odds ratio [OR], 2.42; 95% CI, 1.50-3.91; P <.001; I2 = 21%; response: 60.4% vs 38.6%; OR, 2.34; 95% CI, 1.46-3.75; P <.001; I2 = 41%). With BLT, subgroup analysis based on follow-up times also showed better remission (<4 weeks: 27.4% vs 9.2%; OR, 3.59; 95% CI, 1.45-8.88; P = .005; I2 = 0% and >4 weeks: 46.6% vs 29.1%; OR, 2.18; 95% CI, 1.19-4.00; P = .01; I2 = 47%) and response (<4 weeks: 55.6% vs 27.4%; OR, 3.65; 95% CI, 1.81-7.33; P <.001; I2 = 35% and >4 weeks: 63.0% vs 44.9%; OR, 1.79; 95% CI, 1.01-3.17; P = .04; I2 = 32%) rates.</p><p><strong>Conclusions and relevance: </strong>Results of this systematic review and meta-analysis reveal that BLT was an effective adjunctive treatment for nonseasonal depressive disorders. Additionally, results suggest that BLT may improve the response time to the initial treatment.</p>","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":"38-46"},"PeriodicalIF":22.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1001/jamapsychiatry.2024.3543
Sarah Herzog, Elizabeth A Bartlett, Francesca Zanderigo, Hanga C Galfalvy, Ainsley Burke, Akiva Mintz, Mike Schmidt, Eric Hauser, Yung-Yu Huang, Nadine Melhem, M Elizabeth Sublette, Jeffrey M Miller, J John Mann
<p><strong>Importance: </strong>Brain translocator protein 18k Da (TSPO) binding, a putative marker of neuroinflammatory processes (eg, gliosis), is associated with stress and elevated in depressed and suicidal populations. However, it is unclear whether neuroinflammation moderates the impact of daily life stress on suicidal ideation and negative affect, thereby increasing risk for suicidal behavior.</p><p><strong>Objective: </strong>To examine the association of TSPO binding in participants with depression with real-world daily experiences of acute stress-related suicidal ideation and negative affect, as well as history of suicidal behavior and clinician-rated suicidal ideation.</p><p><strong>Design, setting, and participants: </strong>Data for this cross-sectional study were collected from June 2019 through July 2023. Procedures were conducted at a hospital-based research center in New York, New York. Participants were recruited via clinical referrals, the Columbia University research subject web portal, and from responses to internet advertisements. Of 148 participants who signed informed consent for study protocols, 53 adults aged 18 to 60 years who met DSM-5 diagnostic criteria for current major depressive disorder completed procedures with approved data and were enrolled. Participants were free of schizophrenia spectrum disorders, active physical illness, cognitive impairment, and substance intoxication or withdrawal at the time of scan.</p><p><strong>Exposures: </strong>All participants underwent positron emission tomography imaging of TSPO binding with 11C-ER176 and concurrent arterial blood sampling.</p><p><strong>Main outcome and measures: </strong>A weighted average of 11C-ER176 total distribution volume (VT) was computed across 11 a priori brain regions and made up the primary outcome measure. Clinician-rated suicidal ideation was measured via the Beck Scale for Suicidal Ideation (BSS). A subset of participants (n = 21) completed 7 days of ecological momentary assessment (EMA), reporting daily on suicidal ideation, negative affect, and stressors.</p><p><strong>Results: </strong>In the overall sample of 53 participants (mean [SD] age, 29.5 [9.8] years; 37 [69.8%] female and 16 [30.2%] male), 11C-ER176 VT was associated at trend levels with clinician-rated suicidal ideation severity (β, 0.19; 95% CI, -0.03 to 0.39; P = .09) and did not differ by suicide attempt history (n = 15; β, 0.18; 95% CI, -0.04 to 0.37; P = .11). Exploratory analyses indicated that presence of suicidal ideation (on BSS or EMA) was associated with higher 11C-ER176 VT (β, 0.21; 95% CI, 0.01 to 0.98; P = .045). In 21 participants who completed EMA, 11C-ER176 VT was associated with greater suicidal ideation and negative affect during EMA periods with stressors compared with nonstress periods (β, 0.12; SE, 0.06; 95% CI, 0.01 to 0.23; P = .03 and β, 0.19; SE, 0.06; 95% CI, 0.08 to 0.30; P < .001, respectively).</p><p><strong>Conclusion and relevance: </strong>TSPO bindi
{"title":"Neuroinflammation, Stress-Related Suicidal Ideation, and Negative Mood in Depression.","authors":"Sarah Herzog, Elizabeth A Bartlett, Francesca Zanderigo, Hanga C Galfalvy, Ainsley Burke, Akiva Mintz, Mike Schmidt, Eric Hauser, Yung-Yu Huang, Nadine Melhem, M Elizabeth Sublette, Jeffrey M Miller, J John Mann","doi":"10.1001/jamapsychiatry.2024.3543","DOIUrl":"10.1001/jamapsychiatry.2024.3543","url":null,"abstract":"<p><strong>Importance: </strong>Brain translocator protein 18k Da (TSPO) binding, a putative marker of neuroinflammatory processes (eg, gliosis), is associated with stress and elevated in depressed and suicidal populations. However, it is unclear whether neuroinflammation moderates the impact of daily life stress on suicidal ideation and negative affect, thereby increasing risk for suicidal behavior.</p><p><strong>Objective: </strong>To examine the association of TSPO binding in participants with depression with real-world daily experiences of acute stress-related suicidal ideation and negative affect, as well as history of suicidal behavior and clinician-rated suicidal ideation.</p><p><strong>Design, setting, and participants: </strong>Data for this cross-sectional study were collected from June 2019 through July 2023. Procedures were conducted at a hospital-based research center in New York, New York. Participants were recruited via clinical referrals, the Columbia University research subject web portal, and from responses to internet advertisements. Of 148 participants who signed informed consent for study protocols, 53 adults aged 18 to 60 years who met DSM-5 diagnostic criteria for current major depressive disorder completed procedures with approved data and were enrolled. Participants were free of schizophrenia spectrum disorders, active physical illness, cognitive impairment, and substance intoxication or withdrawal at the time of scan.</p><p><strong>Exposures: </strong>All participants underwent positron emission tomography imaging of TSPO binding with 11C-ER176 and concurrent arterial blood sampling.</p><p><strong>Main outcome and measures: </strong>A weighted average of 11C-ER176 total distribution volume (VT) was computed across 11 a priori brain regions and made up the primary outcome measure. Clinician-rated suicidal ideation was measured via the Beck Scale for Suicidal Ideation (BSS). A subset of participants (n = 21) completed 7 days of ecological momentary assessment (EMA), reporting daily on suicidal ideation, negative affect, and stressors.</p><p><strong>Results: </strong>In the overall sample of 53 participants (mean [SD] age, 29.5 [9.8] years; 37 [69.8%] female and 16 [30.2%] male), 11C-ER176 VT was associated at trend levels with clinician-rated suicidal ideation severity (β, 0.19; 95% CI, -0.03 to 0.39; P = .09) and did not differ by suicide attempt history (n = 15; β, 0.18; 95% CI, -0.04 to 0.37; P = .11). Exploratory analyses indicated that presence of suicidal ideation (on BSS or EMA) was associated with higher 11C-ER176 VT (β, 0.21; 95% CI, 0.01 to 0.98; P = .045). In 21 participants who completed EMA, 11C-ER176 VT was associated with greater suicidal ideation and negative affect during EMA periods with stressors compared with nonstress periods (β, 0.12; SE, 0.06; 95% CI, 0.01 to 0.23; P = .03 and β, 0.19; SE, 0.06; 95% CI, 0.08 to 0.30; P < .001, respectively).</p><p><strong>Conclusion and relevance: </strong>TSPO bindi","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":"85-93"},"PeriodicalIF":22.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11541744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 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":"10.1001/jamapsychiatry.2024.3592","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":"8-9"},"PeriodicalIF":22.5,"publicationDate":"2025-01-01","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 : 2024-12-23DOI: 10.1001/jamapsychiatry.2024.4145
Jayani Jayawardhana, Jialin Hou, Patricia Freeman, Jeffery C Talbert
<p><strong>Importance: </strong>Whether state implementation of medical and recreational cannabis laws is associated with increased cannabis use disorder (CUD) and/or cannabis poisoning among adults is not evident.</p><p><strong>Objective: </strong>To examine state-level medical and recreational cannabis laws' associations with CUD and cannabis poisoning, overall and by sex and age subgroups.</p><p><strong>Design, setting, and participants: </strong>In this longitudinal cohort study, state-level CUD and cannabis poisoning diagnoses from January 2011 to December 2021 were examined across all 50 US states and the District of Columbia before and after the implementation of medical and recreational cannabis laws (MCLs and RCLs, respectively) using a staggered adoption difference-in-differences approach. Event studies were conducted to estimate the magnitude of the association for each year-quarter relative to the time of each policy implementation. This study was conducted among all adults aged 18 to 64 years enrolled in the Merative MarketScan Commercial Claims and Encounters Database, a database of employer-sponsored health insurance enrollees, with 1 year or more of continuous enrollment from 2011 to 2021. Data analysis was performed from January to August 2024.</p><p><strong>Exposures: </strong>State implementation of an MCL, opening a medical cannabis dispensary (MCD), allowing home cultivation of medical cannabis (HC-MC), and passage of an RCL.</p><p><strong>Main outcomes and measures: </strong>CUD and cannabis poisoning diagnoses per 100 000 enrollees per quarter.</p><p><strong>Results: </strong>This study included 110 256 536 enrollees, of whom 56 843 030 (52%) were female and the mean (SD) enrollee age was 41.0 (13.5) years. MCLs were associated with significant increases in CUD and cannabis poisoning by 31.09 (95% CI, 20.20-41.99; P < .001) and 0.76 (95% CI, 0.52-1.00; P < .001) diagnoses per 100 000 enrollees per quarter, respectively, and RCLs were associated with a significant increase in cannabis poisoning by 0.34 (95% CI, 0.19-0.48; P < .001) per 100 000 enrollees per quarter in states with RCLs compared to states without these laws. No significant associations were observed for MCDs or HC-MC. Relative increases in CUD associated with MCLs were higher among female enrollees and among enrollees aged 35 to 44 years compared with male enrollees and other age groups, respectively. Sensitivity analysis results of 2011 to 2019 data were consistent with the 2011 to 2021 results.</p><p><strong>Conclusions and relevance: </strong>In this longitudinal cohort study, MCLs were associated with increased CUD and cannabis poisoning diagnoses, and RCLs were associated with increased cannabis poisoning in adults aged 18 to 64 years with employer-sponsored health insurance. Communities with increased access to cannabis may experience increased health care use and costs due to increases in cannabis poisoning and CUD, and new clinical and policy intervent
{"title":"Association of State Cannabis Legalization With Cannabis Use Disorder and Cannabis Poisoning.","authors":"Jayani Jayawardhana, Jialin Hou, Patricia Freeman, Jeffery C Talbert","doi":"10.1001/jamapsychiatry.2024.4145","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.4145","url":null,"abstract":"<p><strong>Importance: </strong>Whether state implementation of medical and recreational cannabis laws is associated with increased cannabis use disorder (CUD) and/or cannabis poisoning among adults is not evident.</p><p><strong>Objective: </strong>To examine state-level medical and recreational cannabis laws' associations with CUD and cannabis poisoning, overall and by sex and age subgroups.</p><p><strong>Design, setting, and participants: </strong>In this longitudinal cohort study, state-level CUD and cannabis poisoning diagnoses from January 2011 to December 2021 were examined across all 50 US states and the District of Columbia before and after the implementation of medical and recreational cannabis laws (MCLs and RCLs, respectively) using a staggered adoption difference-in-differences approach. Event studies were conducted to estimate the magnitude of the association for each year-quarter relative to the time of each policy implementation. This study was conducted among all adults aged 18 to 64 years enrolled in the Merative MarketScan Commercial Claims and Encounters Database, a database of employer-sponsored health insurance enrollees, with 1 year or more of continuous enrollment from 2011 to 2021. Data analysis was performed from January to August 2024.</p><p><strong>Exposures: </strong>State implementation of an MCL, opening a medical cannabis dispensary (MCD), allowing home cultivation of medical cannabis (HC-MC), and passage of an RCL.</p><p><strong>Main outcomes and measures: </strong>CUD and cannabis poisoning diagnoses per 100 000 enrollees per quarter.</p><p><strong>Results: </strong>This study included 110 256 536 enrollees, of whom 56 843 030 (52%) were female and the mean (SD) enrollee age was 41.0 (13.5) years. MCLs were associated with significant increases in CUD and cannabis poisoning by 31.09 (95% CI, 20.20-41.99; P < .001) and 0.76 (95% CI, 0.52-1.00; P < .001) diagnoses per 100 000 enrollees per quarter, respectively, and RCLs were associated with a significant increase in cannabis poisoning by 0.34 (95% CI, 0.19-0.48; P < .001) per 100 000 enrollees per quarter in states with RCLs compared to states without these laws. No significant associations were observed for MCDs or HC-MC. Relative increases in CUD associated with MCLs were higher among female enrollees and among enrollees aged 35 to 44 years compared with male enrollees and other age groups, respectively. Sensitivity analysis results of 2011 to 2019 data were consistent with the 2011 to 2021 results.</p><p><strong>Conclusions and relevance: </strong>In this longitudinal cohort study, MCLs were associated with increased CUD and cannabis poisoning diagnoses, and RCLs were associated with increased cannabis poisoning in adults aged 18 to 64 years with employer-sponsored health insurance. Communities with increased access to cannabis may experience increased health care use and costs due to increases in cannabis poisoning and CUD, and new clinical and policy intervent","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":""},"PeriodicalIF":22.5,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876404","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 : 2024-12-18DOI: 10.1001/jamapsychiatry.2024.3996
Lori L. Davis, Saloni Behl, Daniel Lee, Hui Zeng, Taisa Skubiak, Shelley Weaver, Nanco Hefting, Klaus Groes Larsen, Mary Hobart
ImportanceNew pharmacotherapy options are needed for posttraumatic stress disorder (PTSD).ObjectiveTo investigate the efficacy, safety, and tolerability of brexpiprazole and sertraline combination treatment (brexpiprazole + sertraline) compared with sertraline + placebo for PTSD.Design, Setting, and ParticipantsThis was a parallel-design, double-blind, randomized clinical trial conducted from October 2019 to August 2023. The study had a 1-week, placebo run-in period followed by an 11-week, double-blind, randomized, active-controlled, parallel-arm period (with 21-day follow-up) and took place at 86 clinical trial sites in the US. Adult outpatients with PTSD were enrolled (volunteer sample).InterventionsOral brexpiprazole 2 to 3 mg per day (flexible dose) + sertraline 150 mg per day or sertraline 150 mg per day + placebo (1:1 ratio) for 11 weeks.Main Outcomes and MeasuresThe primary end point was change in Clinician-Administered PTSD Scale for <jats:italic>DSM-5</jats:italic> (CAPS-5) total score (which measures the severity of 20 PTSD symptoms) from randomization (week 1) to week 10 for brexpiprazole + sertraline vs sertraline + placebo. Safety assessments included adverse events.ResultsA total of 1327 individuals were assessed for eligibility. After 878 screen failures, 416 participants (mean [SD] age, 37.4 [11.9] years; 310 female [74.5%]) were randomized. Completion rates were 137 of 214 participants (64.0%) for brexpiprazole + sertraline and 113 of 202 participants (55.9%) for sertraline + placebo. At week 10, brexpiprazole + sertraline demonstrated statistically significant greater improvement in CAPS-5 total score (mean [SD] at randomization, 38.4 [7.2]; LS mean [SE] change, −19.2 [1.2]; n = 148) than sertraline + placebo (randomization, 38.7 [7.8]; change, −13.6 [1.2]; n = 134), with LS mean difference, −5.59 (95% CI, −8.79 to −2.38; <jats:italic>P</jats:italic> &lt; .001). All key secondary and other efficacy end points were also met. Treatment-emergent adverse events with incidence of 5% or greater for brexpiprazole + sertraline (and corresponding incidences for sertraline + placebo) were nausea (25 of 205 [12.2%] and 23 of 196 [11.7%]), fatigue (14 of 205 [6.8%] and 8 of 196 [4.1%]), weight increase (12 of 205 [5.9%] and 3 of 196 [1.5%]), and somnolence (11 of 205 [5.4%] and 5 of 196 [2.6%]). Discontinuation rates due to adverse events were 8 of 205 participants (3.9%) for brexpiprazole + sertraline and 20 of 196 participants (10.2%) for sertraline + placebo.Conclusions and RelevanceResults of this randomized clinical trial show that brexpiprazole + sertraline combination treatment statistically significantly improved PTSD symptoms vs sertraline + placebo, indicating its potential as a new efficacious treatment for PTSD. Brexpiprazole + sertraline was tolerated by most participants, with a safety profile consistent with that of brexpiprazole in approved indications.Trial RegistrationClinicalTrials.gov Identifier: <jats:ext-link x
{"title":"Brexpiprazole and Sertraline Combination Treatment in Posttraumatic Stress Disorder","authors":"Lori L. Davis, Saloni Behl, Daniel Lee, Hui Zeng, Taisa Skubiak, Shelley Weaver, Nanco Hefting, Klaus Groes Larsen, Mary Hobart","doi":"10.1001/jamapsychiatry.2024.3996","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.3996","url":null,"abstract":"ImportanceNew pharmacotherapy options are needed for posttraumatic stress disorder (PTSD).ObjectiveTo investigate the efficacy, safety, and tolerability of brexpiprazole and sertraline combination treatment (brexpiprazole + sertraline) compared with sertraline + placebo for PTSD.Design, Setting, and ParticipantsThis was a parallel-design, double-blind, randomized clinical trial conducted from October 2019 to August 2023. The study had a 1-week, placebo run-in period followed by an 11-week, double-blind, randomized, active-controlled, parallel-arm period (with 21-day follow-up) and took place at 86 clinical trial sites in the US. Adult outpatients with PTSD were enrolled (volunteer sample).InterventionsOral brexpiprazole 2 to 3 mg per day (flexible dose) + sertraline 150 mg per day or sertraline 150 mg per day + placebo (1:1 ratio) for 11 weeks.Main Outcomes and MeasuresThe primary end point was change in Clinician-Administered PTSD Scale for <jats:italic>DSM-5</jats:italic> (CAPS-5) total score (which measures the severity of 20 PTSD symptoms) from randomization (week 1) to week 10 for brexpiprazole + sertraline vs sertraline + placebo. Safety assessments included adverse events.ResultsA total of 1327 individuals were assessed for eligibility. After 878 screen failures, 416 participants (mean [SD] age, 37.4 [11.9] years; 310 female [74.5%]) were randomized. Completion rates were 137 of 214 participants (64.0%) for brexpiprazole + sertraline and 113 of 202 participants (55.9%) for sertraline + placebo. At week 10, brexpiprazole + sertraline demonstrated statistically significant greater improvement in CAPS-5 total score (mean [SD] at randomization, 38.4 [7.2]; LS mean [SE] change, −19.2 [1.2]; n = 148) than sertraline + placebo (randomization, 38.7 [7.8]; change, −13.6 [1.2]; n = 134), with LS mean difference, −5.59 (95% CI, −8.79 to −2.38; <jats:italic>P</jats:italic> &amp;lt; .001). All key secondary and other efficacy end points were also met. Treatment-emergent adverse events with incidence of 5% or greater for brexpiprazole + sertraline (and corresponding incidences for sertraline + placebo) were nausea (25 of 205 [12.2%] and 23 of 196 [11.7%]), fatigue (14 of 205 [6.8%] and 8 of 196 [4.1%]), weight increase (12 of 205 [5.9%] and 3 of 196 [1.5%]), and somnolence (11 of 205 [5.4%] and 5 of 196 [2.6%]). Discontinuation rates due to adverse events were 8 of 205 participants (3.9%) for brexpiprazole + sertraline and 20 of 196 participants (10.2%) for sertraline + placebo.Conclusions and RelevanceResults of this randomized clinical trial show that brexpiprazole + sertraline combination treatment statistically significantly improved PTSD symptoms vs sertraline + placebo, indicating its potential as a new efficacious treatment for PTSD. Brexpiprazole + sertraline was tolerated by most participants, with a safety profile consistent with that of brexpiprazole in approved indications.Trial RegistrationClinicalTrials.gov Identifier: <jats:ext-link x","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"53 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841809","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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