Pub Date : 2025-12-23DOI: 10.1001/jamapsychiatry.2025.3893
Danielle N Pratt,Nashya Linares,Catherine Spencer,Gabrielle M Olson,Maeve Hoffman,Sophia Parmacek,Lauren E Lee,Luz Maria Alliende,Vanessa Zarubin,Dwight Dickinson,James M Gold,Vijay A Mittal
ImportanceCognition is impaired in people with schizophrenia, affecting quality of life and functioning. Therefore, it is important to understand and characterize this impairment.ObjectiveTo update and revisit the evidence for a central processing speed impairment in people with schizophrenia and examine the factors that moderate this impairment.Data SourcesArticles were identified through the PubMed and PsycINFO databases from February 1, 2009, through November 2, 2023.Study SelectionStudies were included if they reported on a symbol coding test and at least 2 additional cognitive tests from 2 other cognitive domains, contrasted people with schizophrenia to controls, used contemporary diagnostic criteria, included sufficient detail to calculate Hedges g effect sizes, and were reported in English. Of 4530 identified articles, 115 studies met inclusion criteria.Data Extraction and SynthesisThis study followed the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines. Means, SDs, and sample sizes were extracted for all cognitive tests that appeared in at least 3 of the 115 studies. Data were entered and visually checked by independent extractors. Data were generally pooled using random-effects models, except when specified. Measures of homogeneity (Q and I2) and publication bias (fail-safe N and funnel plots) were also examined.Main Outcomes and MeasuresThe primary outcome was the degree of cognitive impairment (Hedges g) observed for people with schizophrenia in 50 cognitive tests, focusing on symbol coding tests of processing speed. Further, this study aimed to identify clinical and study characteristics that moderate the degree of symbol coding impairment.ResultsData were available for 10 114 people with schizophrenia and 13 235 controls from 115 studies. Symbol coding tasks were among the most impaired (g = -1.52; 95% CI, -1.65 to -1.40) but did not reliably differ from 15 other tests. Intelligence quotient and age difference from controls, composition of sex assigned at birth, inpatient status, and whether the sample included schizoaffective and schizophreniform diagnoses all moderated the degree of symbol coding impairment.Conclusions and RelevanceThis meta-analysis provides insight into the consistency of the processing speed impairment for people with schizophrenia. Findings support that this impairment may be central to global cognitive impairments, which might be a consequence of altered brain connectivity.
{"title":"Processing Speed Impairment in Schizophrenia: An Updated Systematic Review and Meta-Analysis.","authors":"Danielle N Pratt,Nashya Linares,Catherine Spencer,Gabrielle M Olson,Maeve Hoffman,Sophia Parmacek,Lauren E Lee,Luz Maria Alliende,Vanessa Zarubin,Dwight Dickinson,James M Gold,Vijay A Mittal","doi":"10.1001/jamapsychiatry.2025.3893","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.3893","url":null,"abstract":"ImportanceCognition is impaired in people with schizophrenia, affecting quality of life and functioning. Therefore, it is important to understand and characterize this impairment.ObjectiveTo update and revisit the evidence for a central processing speed impairment in people with schizophrenia and examine the factors that moderate this impairment.Data SourcesArticles were identified through the PubMed and PsycINFO databases from February 1, 2009, through November 2, 2023.Study SelectionStudies were included if they reported on a symbol coding test and at least 2 additional cognitive tests from 2 other cognitive domains, contrasted people with schizophrenia to controls, used contemporary diagnostic criteria, included sufficient detail to calculate Hedges g effect sizes, and were reported in English. Of 4530 identified articles, 115 studies met inclusion criteria.Data Extraction and SynthesisThis study followed the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines. Means, SDs, and sample sizes were extracted for all cognitive tests that appeared in at least 3 of the 115 studies. Data were entered and visually checked by independent extractors. Data were generally pooled using random-effects models, except when specified. Measures of homogeneity (Q and I2) and publication bias (fail-safe N and funnel plots) were also examined.Main Outcomes and MeasuresThe primary outcome was the degree of cognitive impairment (Hedges g) observed for people with schizophrenia in 50 cognitive tests, focusing on symbol coding tests of processing speed. Further, this study aimed to identify clinical and study characteristics that moderate the degree of symbol coding impairment.ResultsData were available for 10 114 people with schizophrenia and 13 235 controls from 115 studies. Symbol coding tasks were among the most impaired (g = -1.52; 95% CI, -1.65 to -1.40) but did not reliably differ from 15 other tests. Intelligence quotient and age difference from controls, composition of sex assigned at birth, inpatient status, and whether the sample included schizoaffective and schizophreniform diagnoses all moderated the degree of symbol coding impairment.Conclusions and RelevanceThis meta-analysis provides insight into the consistency of the processing speed impairment for people with schizophrenia. Findings support that this impairment may be central to global cognitive impairments, which might be a consequence of altered brain connectivity.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"38 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145807911","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 : 2025-12-23DOI: 10.1001/jamapsychiatry.2025.4262
Gang Wang,Matthew A Spear,Wen Luo
{"title":"Restricting Liafensine on the Basis of ANK3 Genotype-More Evidence Needed-Reply.","authors":"Gang Wang,Matthew A Spear,Wen Luo","doi":"10.1001/jamapsychiatry.2025.4262","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.4262","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"28 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145807887","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 : 2025-12-23DOI: 10.1001/jamapsychiatry.2025.3874
Kelly Fung,Loreen Straub,Brian T Bateman,Sonia Hernandez-Diaz,Gregory Brill,Yanmin Zhu,Lee S Cohen,Kathryn J Gray,Krista F Huybrechts
ImportanceSleep disturbances are common in pregnancy and often treated with nonbenzodiazepine sedative hypnotics (Z-drugs). However, there is limited evidence on the fetal safety of Z-drugs.ObjectiveTo evaluate whether Z-drug exposure in the first trimester of pregnancy is associated with an increased risk of congenital malformations.Design, Setting, and ParticipantsThis US population-based cohort study evaluated health care utilization data from publicly insured beneficiaries in the Medicaid database (2000-2018) and commercially insured beneficiaries in the Merative MarketScan database (2003-2020). Participants were pregnant individuals and their liveborn infants, with maternal enrollment from 90 days before pregnancy to 30 days after delivery and infant enrollment for 90 days after birth unless death occurred sooner. Data analysis was performed from November 2023 to April 2025.ExposureAt least 1 dispensing of Z-drugs (zaleplon, eszopiclone, or zolpidem) in the first trimester of pregnancy compared with no dispensing.Main Outcomes and MeasuresMajor congenital malformations were identified using linked maternal and infant claims. The risks of any major congenital malformation, organ-specific malformations, and individual malformations in pregnancies with Z-drug exposure in the first trimester were compared with the risks in unexposed pregnancies. Relative risks (RRs) and 95% CIs were estimated. Propensity score fine stratification weights were used to control for confounders.ResultsA total of 4 281 579 pregnancies were identified (mean [SD] maternal age at delivery, 25.2 [6.0] years in Medicaid and 31.6 [4.6] years in MarketScan). First-trimester Z-drug exposure was identified in 11 652 (0.5%) of 2 506 106 pregnancies in Medicaid and 10 862 (0.6%) of 1 775 473 pregnancies in MarketScan; 92.1% of exposed pregnancies had zolpidem exposure. The adjusted pooled RR for malformations overall was 1.01 (95% CI, 0.95-1.08). While adjusted pooled RRs were increased for abdominal wall defects (1.46; 95% CI, 0.89-2.38), tetralogy of Fallot (1.45; 95% CI, 0.86-2.46), and neural tube defects (1.62; 95% CI, 0.96-2.74), these associations were imprecisely estimated, driven by the Medicaid cohort and not replicated in the MarketScan cohort. Results were consistent across multiple sensitivity analyses.Conclusions and RelevanceThese findings suggest that Z-drug exposure in the first trimester of pregnancy is not associated with a meaningful elevation in the risk of congenital malformations overall, nor was there a consistent signal observed for organ-specific or uncommon, individual malformations examined.
{"title":"Z-Drug Use in the First Trimester of Pregnancy and Risk of Congenital Malformations.","authors":"Kelly Fung,Loreen Straub,Brian T Bateman,Sonia Hernandez-Diaz,Gregory Brill,Yanmin Zhu,Lee S Cohen,Kathryn J Gray,Krista F Huybrechts","doi":"10.1001/jamapsychiatry.2025.3874","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.3874","url":null,"abstract":"ImportanceSleep disturbances are common in pregnancy and often treated with nonbenzodiazepine sedative hypnotics (Z-drugs). However, there is limited evidence on the fetal safety of Z-drugs.ObjectiveTo evaluate whether Z-drug exposure in the first trimester of pregnancy is associated with an increased risk of congenital malformations.Design, Setting, and ParticipantsThis US population-based cohort study evaluated health care utilization data from publicly insured beneficiaries in the Medicaid database (2000-2018) and commercially insured beneficiaries in the Merative MarketScan database (2003-2020). Participants were pregnant individuals and their liveborn infants, with maternal enrollment from 90 days before pregnancy to 30 days after delivery and infant enrollment for 90 days after birth unless death occurred sooner. Data analysis was performed from November 2023 to April 2025.ExposureAt least 1 dispensing of Z-drugs (zaleplon, eszopiclone, or zolpidem) in the first trimester of pregnancy compared with no dispensing.Main Outcomes and MeasuresMajor congenital malformations were identified using linked maternal and infant claims. The risks of any major congenital malformation, organ-specific malformations, and individual malformations in pregnancies with Z-drug exposure in the first trimester were compared with the risks in unexposed pregnancies. Relative risks (RRs) and 95% CIs were estimated. Propensity score fine stratification weights were used to control for confounders.ResultsA total of 4 281 579 pregnancies were identified (mean [SD] maternal age at delivery, 25.2 [6.0] years in Medicaid and 31.6 [4.6] years in MarketScan). First-trimester Z-drug exposure was identified in 11 652 (0.5%) of 2 506 106 pregnancies in Medicaid and 10 862 (0.6%) of 1 775 473 pregnancies in MarketScan; 92.1% of exposed pregnancies had zolpidem exposure. The adjusted pooled RR for malformations overall was 1.01 (95% CI, 0.95-1.08). While adjusted pooled RRs were increased for abdominal wall defects (1.46; 95% CI, 0.89-2.38), tetralogy of Fallot (1.45; 95% CI, 0.86-2.46), and neural tube defects (1.62; 95% CI, 0.96-2.74), these associations were imprecisely estimated, driven by the Medicaid cohort and not replicated in the MarketScan cohort. Results were consistent across multiple sensitivity analyses.Conclusions and RelevanceThese findings suggest that Z-drug exposure in the first trimester of pregnancy is not associated with a meaningful elevation in the risk of congenital malformations overall, nor was there a consistent signal observed for organ-specific or uncommon, individual malformations examined.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"24 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145807889","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 : 2025-12-23DOI: 10.1001/jamapsychiatry.2025.3883
Robert H Pietrzak,Ian C Fischer,Brandon Nichter,Irina Esterlis,John H Krystal,Christine Y Moutier,Maria A Oquendo,Dilip V Jeste,Peter Jongho Na
{"title":"Social Determinants of Health and Suicide Risk in US Military Veterans.","authors":"Robert H Pietrzak,Ian C Fischer,Brandon Nichter,Irina Esterlis,John H Krystal,Christine Y Moutier,Maria A Oquendo,Dilip V Jeste,Peter Jongho Na","doi":"10.1001/jamapsychiatry.2025.3883","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.3883","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"84 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145807912","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 : 2025-12-23DOI: 10.1001/jamapsychiatry.2025.4259
David Curtis
{"title":"Restricting Liafensine on the Basis of ANK3 Genotype-More Evidence Needed.","authors":"David Curtis","doi":"10.1001/jamapsychiatry.2025.4259","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.4259","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"1 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145807888","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 : 2025-12-17DOI: 10.1001/jamapsychiatry.2025.3803
David Popovic,Clara Weyer,Dominic B Dwyer,Sian Lowri Griffiths,Paris Alexandros Lalousis,Nicholas M Barnes,Clara Vetter,Lisa-Maria Neuner,Madalina-Octavia Buciuman,Elif Sarisik,Marco Paolini,Theresa Lichtenstein,Lana Kambeitz-Ilankovic,Joseph Kambeitz,Stephan Ruhrmann,Katharine Chisholm,Frauke Schultze-Lutter,Peter Falkai,Kolja Schiltz,Johann Steiner,Michael Ziller,Giulio Pergola,Giuseppe Blasi,Alessandro Bertolino,Georg Romer,Rebekka Lencer,Udo Dannlowski,Raimo K R Salokangas,Christos Pantelis,Paolo Brambilla,Stefan Borgwardt,Stephen J Wood,Eva Meisenzahl,Nikolaos Koutsouleris,Rachel Upthegrove,
ImportanceInflammation is increasingly implicated in the pathophysiology of mood and psychotic disorders. Integrating blood biomarkers and brain imaging may help uncover mechanistic pathways and guide targeted interventions.ObjectiveTo identify shared and distinct multivariate patterns of peripheral inflammation and gray matter volume (GMV) in early-stage depressive and psychotic disorders using a transdiagnostic machine learning approach.Design, Setting, and ParticipantsThe naturalistic multicenter PRONIA study was conducted between February 2014 and May 2019 with a follow-up period of up to 36 months; baseline data were analyzed between August 2021 and April 2024. Eight sites, including inpatient and outpatient facilities, in 5 European countries (Germany, Italy, Switzerland, Finland, and the United Kingdom) were included. The study included individuals with recent-onset depression (ROD, n = 163) or psychosis (ROP, n = 177) or clinical high-risk states for psychosis (CHR-P, n = 172), all with minimal medication exposure, and healthy control (HC) individuals (n = 166).ExposuresStructural magnetic resonance imaging (MRI), peripheral assays of cytokines (eg, interleukin [IL] 6, IL-1β, tumor necrosis factor [TNF] α, C-reactive protein [CRP], brain-derived neurotrophic factor [BDNF], S100 calcium-binding protein B [S100B]); clinical assessments; neurocognitive testing.Main Outcomes and MeasuresAfter data collection, sparse partial least squares was used to identify latent brain-blood signatures. Support vector machine classification evaluated psychosocial and neurocognitive predictors of signature expression using repeated nested cross-validation.ResultsA total of 678 participants (346 [51.0%] female; median [IQR] age, 24.0 [20.9-28.9] years) were included. Four signatures were identified. A psychosis signature (ρ = 0.27; P = .002) differentiated ROP from CHR-P with elevated IL-6, TNF-α, and reduced CRP, alongside GMV shifts in corticothalamic circuits. A depression signature (ρ = 0.19; P = .02) differentiated ROD from HC individuals with elevated IL-1β, IL-2, IL-4, S100B, and BDNF and GMV reductions in limbic regions. Additional signatures reflected age (ρ = 0.67) and sex or MRI quality (ρ = 0.53). Psychosocial features, including a differential childhood trauma pattern, predicted both the psychosis (balanced accuracy [BAC] = 67.2%) and depression (BAC = 78.0%) signatures. Cognitive performance predicted only the psychosis signature (BAC = 65.1%).Conclusions and RelevanceIn this study, early-stage depression and psychosis exhibited distinct neurobiological signatures involving immune and neuroanatomical markers, challenging fully dimensional disease models. These signatures are shaped by childhood trauma and cognition and may support biologically informed early interventions.
炎症越来越多地与情绪和精神障碍的病理生理有关。整合血液生物标志物和脑成像可能有助于揭示机制途径并指导有针对性的干预措施。目的利用跨诊断机器学习方法识别早期抑郁症和精神病患者外周炎症和灰质体积（GMV）的共同和独特的多变量模式。设计、环境和参与者自然多中心PRONIA研究于2014年2月至2019年5月进行，随访期长达36个月；基线数据在2021年8月至2024年4月期间进行了分析。包括5个欧洲国家（德国、意大利、瑞士、芬兰和联合王国）的8个地点，包括住院和门诊设施。该研究包括新近发作的抑郁症（ROD, n = 163）或精神病（ROP, n = 177）或精神病临床高危状态（chrp, n = 172）的个体，所有患者均有最小的药物暴露，以及健康对照（HC）个体（n = 166）。结构磁共振成像（MRI），细胞因子外周检测（如：白细胞介素[IL] 6、IL-1β、肿瘤坏死因子[TNF] α、c反应蛋白[CRP]、脑源性神经营养因子[BDNF]、S100钙结合蛋白B [S100B]）；临床评估;神经认知测试。收集数据后，使用稀疏偏最小二乘法识别潜在的脑-血特征。支持向量机分类使用重复嵌套交叉验证评估签名表达的社会心理和神经认知预测因子。结果共纳入678例受试者，其中女性346例（51.0%），中位年龄24.0岁（20.9 ~ 28.9）。四个签名被确认。精神病特征(ρ = 0.27; P =。002)将ROP与chrp分化为IL-6、TNF-α升高和CRP降低，同时皮质丘脑回路GMV移位。抑郁特征(ρ = 0.19; P =。02)从IL-1β、IL-2、IL-4、S100B和BDNF升高以及边缘区GMV降低的HC个体中分化出ROD。其他特征反映了年龄（ρ = 0.67）、性别或MRI质量（ρ = 0.53）。心理社会特征，包括不同的童年创伤模式，可以预测精神病（平衡准确率[BAC] = 67.2%）和抑郁症（BAC = 78.0%）的特征。认知表现仅能预测精神病特征（BAC = 65.1%）。在这项研究中，早期抑郁症和精神病表现出不同的神经生物学特征，包括免疫和神经解剖学标记，挑战了全维度疾病模型。这些特征是由童年创伤和认知形成的，可能支持生物学知情的早期干预。
{"title":"Multivariate Brain-Blood Signatures in Early-Stage Depression and Psychosis.","authors":"David Popovic,Clara Weyer,Dominic B Dwyer,Sian Lowri Griffiths,Paris Alexandros Lalousis,Nicholas M Barnes,Clara Vetter,Lisa-Maria Neuner,Madalina-Octavia Buciuman,Elif Sarisik,Marco Paolini,Theresa Lichtenstein,Lana Kambeitz-Ilankovic,Joseph Kambeitz,Stephan Ruhrmann,Katharine Chisholm,Frauke Schultze-Lutter,Peter Falkai,Kolja Schiltz,Johann Steiner,Michael Ziller,Giulio Pergola,Giuseppe Blasi,Alessandro Bertolino,Georg Romer,Rebekka Lencer,Udo Dannlowski,Raimo K R Salokangas,Christos Pantelis,Paolo Brambilla,Stefan Borgwardt,Stephen J Wood,Eva Meisenzahl,Nikolaos Koutsouleris,Rachel Upthegrove, ","doi":"10.1001/jamapsychiatry.2025.3803","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.3803","url":null,"abstract":"ImportanceInflammation is increasingly implicated in the pathophysiology of mood and psychotic disorders. Integrating blood biomarkers and brain imaging may help uncover mechanistic pathways and guide targeted interventions.ObjectiveTo identify shared and distinct multivariate patterns of peripheral inflammation and gray matter volume (GMV) in early-stage depressive and psychotic disorders using a transdiagnostic machine learning approach.Design, Setting, and ParticipantsThe naturalistic multicenter PRONIA study was conducted between February 2014 and May 2019 with a follow-up period of up to 36 months; baseline data were analyzed between August 2021 and April 2024. Eight sites, including inpatient and outpatient facilities, in 5 European countries (Germany, Italy, Switzerland, Finland, and the United Kingdom) were included. The study included individuals with recent-onset depression (ROD, n = 163) or psychosis (ROP, n = 177) or clinical high-risk states for psychosis (CHR-P, n = 172), all with minimal medication exposure, and healthy control (HC) individuals (n = 166).ExposuresStructural magnetic resonance imaging (MRI), peripheral assays of cytokines (eg, interleukin [IL] 6, IL-1β, tumor necrosis factor [TNF] α, C-reactive protein [CRP], brain-derived neurotrophic factor [BDNF], S100 calcium-binding protein B [S100B]); clinical assessments; neurocognitive testing.Main Outcomes and MeasuresAfter data collection, sparse partial least squares was used to identify latent brain-blood signatures. Support vector machine classification evaluated psychosocial and neurocognitive predictors of signature expression using repeated nested cross-validation.ResultsA total of 678 participants (346 [51.0%] female; median [IQR] age, 24.0 [20.9-28.9] years) were included. Four signatures were identified. A psychosis signature (ρ = 0.27; P = .002) differentiated ROP from CHR-P with elevated IL-6, TNF-α, and reduced CRP, alongside GMV shifts in corticothalamic circuits. A depression signature (ρ = 0.19; P = .02) differentiated ROD from HC individuals with elevated IL-1β, IL-2, IL-4, S100B, and BDNF and GMV reductions in limbic regions. Additional signatures reflected age (ρ = 0.67) and sex or MRI quality (ρ = 0.53). Psychosocial features, including a differential childhood trauma pattern, predicted both the psychosis (balanced accuracy [BAC] = 67.2%) and depression (BAC = 78.0%) signatures. Cognitive performance predicted only the psychosis signature (BAC = 65.1%).Conclusions and RelevanceIn this study, early-stage depression and psychosis exhibited distinct neurobiological signatures involving immune and neuroanatomical markers, challenging fully dimensional disease models. These signatures are shaped by childhood trauma and cognition and may support biologically informed early interventions.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"27 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145765056","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 : 2025-12-17DOI: 10.1001/jamapsychiatry.2025.3796
Margarita Panayiotou,Josip Razum,Gudrun Eisele,Shirley B Wang,Eiko I Fried,Zachary D Cohen
ImportanceVersions of the Patient Health Questionnaire (PHQ) such as PHQ-2, PHQ-8, and PHQ-9, are among the leading assessment tools for depression in research and clinical practice. However, important questions remain about its validity, particularly whether responses reflect symptom frequency or the degree to which symptoms are bothersome.ObjectiveTo investigate how participants respond to the PHQ, described as a severity measure by its developers, with instructions about being bothered by symptoms and response options focused on symptom frequency.Design, Setting, and ParticipantsThis study used data from a general population sample collected via Amazon Mechanical Turk (MTurk) and a clinical sample with medium to high depression from the Operationalizing Digital PhenoTyping in the Measurement of Anhedonia (OPTIMA) study. Data were collected between 2022 and 2023.Main Outcomes and MeasuresAfter completing the PHQ-8, participants' interpretation of instructions was assessed via 3 questions: (1) how they would respond to the PHQ sleep item in a hypothetical scenario where they overslept nearly every day but were comfortable with oversleeping; (2) whether they had based their earlier PHQ responses on symptom frequency, being bothered by symptoms, or both; and (3) how they would answer the PHQ in the future, based on these same 3 options.ResultsThe study sample consisted of a general population sample collected via MTurk (n = 503; mean [SD] age, 40.63 [13.62] years; 253 male, 245 female, 3 transgender, 2 other) and a clinical sample with medium to high depression from the OPTIMA study (n = 349; mean [SD] age, 33.44 [12.23] years; 120 male, 216 female, 5 transgender, 8 other). In the hypothetical oversleeping scenario, only 54.7% (n = 275; MTurk) and 15.5% (n = 53; OPTIMA) of participants interpreted the PHQ as instructed (ie, the frequency with which the problems bothered them). When asked how they had responded to the PHQ, only 21.3% (n = 107; MTurk) and 11.7% (n = 40; OPTIMA) of participants interpreted the instructions as instructed and only 22.3% (n = 112; MTurk) and 9.9% (n = 34; OPTIMA) reported they would do so in the future, indicating stability in their interpretation. The current study also found that the PHQ-8 validity varied depending on how participants interpret its instructions.Conclusions and RelevanceThis study identified widespread misinterpretation of the PHQ instructions across community and clinical samples, raising doubts about its validity for both research and clinical decision-making.
{"title":"Interpretation Issues With the Patient Health Questionnaire Instructions.","authors":"Margarita Panayiotou,Josip Razum,Gudrun Eisele,Shirley B Wang,Eiko I Fried,Zachary D Cohen","doi":"10.1001/jamapsychiatry.2025.3796","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.3796","url":null,"abstract":"ImportanceVersions of the Patient Health Questionnaire (PHQ) such as PHQ-2, PHQ-8, and PHQ-9, are among the leading assessment tools for depression in research and clinical practice. However, important questions remain about its validity, particularly whether responses reflect symptom frequency or the degree to which symptoms are bothersome.ObjectiveTo investigate how participants respond to the PHQ, described as a severity measure by its developers, with instructions about being bothered by symptoms and response options focused on symptom frequency.Design, Setting, and ParticipantsThis study used data from a general population sample collected via Amazon Mechanical Turk (MTurk) and a clinical sample with medium to high depression from the Operationalizing Digital PhenoTyping in the Measurement of Anhedonia (OPTIMA) study. Data were collected between 2022 and 2023.Main Outcomes and MeasuresAfter completing the PHQ-8, participants' interpretation of instructions was assessed via 3 questions: (1) how they would respond to the PHQ sleep item in a hypothetical scenario where they overslept nearly every day but were comfortable with oversleeping; (2) whether they had based their earlier PHQ responses on symptom frequency, being bothered by symptoms, or both; and (3) how they would answer the PHQ in the future, based on these same 3 options.ResultsThe study sample consisted of a general population sample collected via MTurk (n = 503; mean [SD] age, 40.63 [13.62] years; 253 male, 245 female, 3 transgender, 2 other) and a clinical sample with medium to high depression from the OPTIMA study (n = 349; mean [SD] age, 33.44 [12.23] years; 120 male, 216 female, 5 transgender, 8 other). In the hypothetical oversleeping scenario, only 54.7% (n = 275; MTurk) and 15.5% (n = 53; OPTIMA) of participants interpreted the PHQ as instructed (ie, the frequency with which the problems bothered them). When asked how they had responded to the PHQ, only 21.3% (n = 107; MTurk) and 11.7% (n = 40; OPTIMA) of participants interpreted the instructions as instructed and only 22.3% (n = 112; MTurk) and 9.9% (n = 34; OPTIMA) reported they would do so in the future, indicating stability in their interpretation. The current study also found that the PHQ-8 validity varied depending on how participants interpret its instructions.Conclusions and RelevanceThis study identified widespread misinterpretation of the PHQ instructions across community and clinical samples, raising doubts about its validity for both research and clinical decision-making.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"20 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145765116","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 : 2025-12-17DOI: 10.1001/jamapsychiatry.2025.3828
Matthew Chinman,Tianxiu Wang,Jessica R Dodge,David A Frank,Jennifer L McCoy,Amy N Cohen
ImportanceVeterans with serious mental illness (SMI) experience a higher prevalence of obesity than the general veteran population; weight loss programs are needed that are tailored to this population.ObjectiveTo evaluate a weight loss program, CoachToFit (CTF), which includes weekly calls from a Veteran Health Administration peer specialist, a Bluetooth-enabled scale and fitness tracker, and a smartphone application that provides health education and tracks steps, goals, and weight.Design, Setting, and ParticipantsThis randomized clinical trial was conducted within the Pittsburgh Veteran Affairs health care system and presents pre-post (6 months) analysis comparing CTF and usual care. Veterans with body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) of 30 or higher and diagnosis of major depressive disorder, bipolar disorder, or schizophrenia were eligible for inclusion. Exclusion criteria included history of bariatric surgery or recent psychiatric hospitalization. The study was conducted from October 1, 2020, to September 30, 2025, and data analysis was conducted from January to October 2025.ExposureRandom assignment to CTF.Main Outcomes and MeasuresThe primary outcomes were weight (in kg), BMI, and cardiorespiratory fitness (meters walked in 6 minutes).ResultsAmong the sample (n = 256), mean (SD) age was 53.5 (13.1) years, 80 participants (31.3%) were female, and 199 (77.7%) were diagnosed with major depressive disorder. Mean (SD) weight loss at 6 months was -3.2 (6.2) kg in the CTF group (n = 128) compared to -1.6 (4.9) kg in the usual care group (P = .05). After adjustment, participants in CTF experienced greater, nonsignificant weight loss compared to usual care, with an adjusted mean difference (AMD) of -1.62 kg (95% CI, -3.38 to 0.14; P = .07). For BMI, the AMD in change between groups at 6 months was -0.56 (95% CI, -1.15 to 0.03; P = .06). Change in meters walked was not statistically significant between groups, with an AMD of 3.53 m (95% CI, -12.87 to 19.92; P = .67). At 6 months, 34 participants (36.6%) from the CTF group lost 5% or more of their body weight compared to 19 (22.4%) in usual care, representing a 1.93-fold greater likelihood in adjusted analyses (95% CI, 0.96-3.91; P = .07). More participants in CTF (n = 21 [22.6%]) lost 7% or more of their body weight compared to usual care (n = 7 [8.2%]), representing a 3.9-fold greater likelihood in adjusted analyses (95% CI, 1.45-10.36; P = .007).Conclusions and RelevanceIn this randomized clinical trial, a weight loss program tailored to veterans with SMI using remote technologies and paraprofessionals demonstrated the potential to help this population lose weight.Trial RegistrationClinicalTrials.gov Identifier: NCT04560335.
患有严重精神疾病（SMI）的退伍军人比一般退伍军人肥胖的患病率更高；需要针对这一人群量身定制的减肥计划。目的评估一项名为CoachToFit （CTF）的减肥计划，该计划包括来自退伍军人健康管理局同行专家的每周电话，蓝牙秤和健身追踪器，以及提供健康教育和跟踪步数、目标和体重的智能手机应用程序。设计、环境和参与者本随机临床试验在匹兹堡退伍军人事务卫生保健系统中进行，并对CTF和常规护理进行了前后（6个月）分析比较。身体质量指数（BMI，以体重公斤除以身高米的平方计算）为30或更高，诊断为重度抑郁症、双相情感障碍或精神分裂症的退伍军人符合入选条件。排除标准包括减肥手术史或近期精神病住院史。研究时间为2020年10月1日至2025年9月30日，数据分析时间为2025年1月至10月。随机分配给CTF。主要结局和测量主要结局是体重（kg）、BMI和心肺健康（6分钟步行米数）。结果样本（n = 256）中，平均（SD）年龄为53.5（13.1）岁，女性80人（31.3%），诊断为重度抑郁症199人（77.7%）。CTF组（n = 128） 6个月时平均（SD）体重减轻-3.2 (6.2)kg，而常规护理组（P = 0.05）为-1.6 (4.9)kg。调整后，与常规护理相比，CTF的参与者经历了更大的、不显著的体重减轻，调整后的平均差异（AMD）为-1.62 kg （95% CI, -3.38至0.14;P = 0.07）。对于BMI， 6个月时各组间AMD的变化为-0.56 （95% CI, -1.15 ~ 0.03; P = 0.06）。两组间行走距离变化无统计学意义，AMD为3.53 m （95% CI, -12.87 ~ 19.92; P = 0.67）。在6个月时，CTF组的34名参与者（36.6%）的体重减轻了5%或更多，而常规护理组的19名参与者（22.4%）的体重减轻了5%或更多，在调整分析中，可能性增加了1.93倍（95% CI, 0.96-3.91; P = 0.07）。CTF组的更多参与者（n = 21[22.6%]）比常规治疗组（n = 7[8.2%]）体重减轻了7%或更多，在调整分析中，可能性增加了3.9倍（95% CI, 1.45-10.36; P = .007）。结论和相关性在这项随机临床试验中，一项针对重度精神障碍退伍军人的减肥计划使用远程技术和辅助专业人员证明了帮助这一人群减肥的潜力。临床试验注册号：NCT04560335。
{"title":"Tailored Weight Loss Programs for Adults With Serious Mental Illness: A Randomized Clinical Trial.","authors":"Matthew Chinman,Tianxiu Wang,Jessica R Dodge,David A Frank,Jennifer L McCoy,Amy N Cohen","doi":"10.1001/jamapsychiatry.2025.3828","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.3828","url":null,"abstract":"ImportanceVeterans with serious mental illness (SMI) experience a higher prevalence of obesity than the general veteran population; weight loss programs are needed that are tailored to this population.ObjectiveTo evaluate a weight loss program, CoachToFit (CTF), which includes weekly calls from a Veteran Health Administration peer specialist, a Bluetooth-enabled scale and fitness tracker, and a smartphone application that provides health education and tracks steps, goals, and weight.Design, Setting, and ParticipantsThis randomized clinical trial was conducted within the Pittsburgh Veteran Affairs health care system and presents pre-post (6 months) analysis comparing CTF and usual care. Veterans with body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) of 30 or higher and diagnosis of major depressive disorder, bipolar disorder, or schizophrenia were eligible for inclusion. Exclusion criteria included history of bariatric surgery or recent psychiatric hospitalization. The study was conducted from October 1, 2020, to September 30, 2025, and data analysis was conducted from January to October 2025.ExposureRandom assignment to CTF.Main Outcomes and MeasuresThe primary outcomes were weight (in kg), BMI, and cardiorespiratory fitness (meters walked in 6 minutes).ResultsAmong the sample (n = 256), mean (SD) age was 53.5 (13.1) years, 80 participants (31.3%) were female, and 199 (77.7%) were diagnosed with major depressive disorder. Mean (SD) weight loss at 6 months was -3.2 (6.2) kg in the CTF group (n = 128) compared to -1.6 (4.9) kg in the usual care group (P = .05). After adjustment, participants in CTF experienced greater, nonsignificant weight loss compared to usual care, with an adjusted mean difference (AMD) of -1.62 kg (95% CI, -3.38 to 0.14; P = .07). For BMI, the AMD in change between groups at 6 months was -0.56 (95% CI, -1.15 to 0.03; P = .06). Change in meters walked was not statistically significant between groups, with an AMD of 3.53 m (95% CI, -12.87 to 19.92; P = .67). At 6 months, 34 participants (36.6%) from the CTF group lost 5% or more of their body weight compared to 19 (22.4%) in usual care, representing a 1.93-fold greater likelihood in adjusted analyses (95% CI, 0.96-3.91; P = .07). More participants in CTF (n = 21 [22.6%]) lost 7% or more of their body weight compared to usual care (n = 7 [8.2%]), representing a 3.9-fold greater likelihood in adjusted analyses (95% CI, 1.45-10.36; P = .007).Conclusions and RelevanceIn this randomized clinical trial, a weight loss program tailored to veterans with SMI using remote technologies and paraprofessionals demonstrated the potential to help this population lose weight.Trial RegistrationClinicalTrials.gov Identifier: NCT04560335.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"15 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145765057","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 : 2025-12-10DOI: 10.1001/jamapsychiatry.2025.3430
Martin Osugo, Thomas Whitehurst, David Erritzoe, Richard Carr, Abhishekh H. Ashok, Lucia Maccioni, Ellis Chika Onwordi, Grazia Rutigliano, Nikola Rahaman, Atheeshaan Arumuham, Antonio de Marvao, Roger N. Gunn, Eugenii A. Rabiner, Tiago Reis Marques, Mattia Veronese, Oliver D. Howes
Importance The involvement of the serotonin system in the pathophysiology of schizophrenia has been proposed for over 60 years, but there has been no prior study to test if there is altered serotonin release in vivo in schizophrenia (to the authors’ knowledge). Objective To investigate serotonin release in vivo in schizophrenia and its association with negative symptoms. It was hypothesized a priori that frontal cortex serotonin release capacity would be lower in schizophrenia compared with healthy controls and that this would be associated with more severe baseline negative symptoms. Design, Setting, and Participants This was a single-center case-control neuroimaging study conducted in London, UK. All participants had dynamic 90-minute [ <jats:sup>11</jats:sup> C]Cimbi-36 positron emission tomography (PET) scans at baseline and 3 hours after oral administration of <jats:sc>d</jats:sc> -amphetamine 0.5mg/kg. Data were collected between 2015 and 2024. Participants included stable adult outpatients with <jats:italic toggle="yes">DSM-5</jats:italic> schizophrenia (antipsychotic free or taking antipsychotics with negligible affinity for 5-hydroxytryptamine receptor 2A [5-HT2A] receptors) and healthy controls matched for age, sex, and body mass index. Main Outcomes and Measures The primary neuroimaging outcome was the group difference in serotonin release capacity, prespecified as the percentage change in frontal cortex [ <jats:sup>11</jats:sup> C]Cimbi-36 binding potential between the baseline and <jats:sc>d</jats:sc> -amphetamine scans. Results A total of 54 individuals were included, 26 with <jats:italic toggle="yes">DSM-5</jats:italic> schizophrenia (mean [SD] age, 33.3 [9.1] years, 16 male [62%]; 21 not taking antipsychotic medication [81%]) and 28 healthy controls (mean [SD] age, 32.0 [9.5] years, 19 male [68%]). Frontal cortex serotonin release was significantly greater in the group with schizophrenia compared with healthy controls (18.0%; 95% CI, 2.5%-33.6%; <jats:italic toggle="yes">P</jats:italic> = .02; Cohen <jats:italic toggle="yes">d</jats:italic> = 0.69). In schizophrenia, greater frontal cortex serotonin release was correlated with more severe baseline negative symptoms (Brief Negative Symptom Scale: Pearson <jats:italic toggle="yes">r</jats:italic> = 0.42; <jats:italic toggle="yes">P</jats:italic> = .04) and poorer functioning (Social Functioning Scale: Pearson <jats:italic toggle="yes">r</jats:italic> = −0.42; <jats:italic toggle="yes">P</jats:italic> = .04). Exploratory analyses showed significantly greater frontal cortex serotonin release in deficit schizophrenia, characterized by primary and enduring negative symptoms, compared with healthy controls (mean difference = 32.3%; FDR-corrected <jats:italic toggle="yes">P</jats:italic> value = 0.001; Cohen <jats:italic toggle="yes">d</jats:italic> = 1.10) and nondeficit schizophrenia (mean difference = 28.9%; FDR-corrected <jats:italic toggle="yes">P</jats:italic> value = 0.004; Cohen <
5 -羟色胺系统参与精神分裂症的病理生理已有60多年的历史，但据作者所知，目前还没有研究证实精神分裂症患者体内5 -羟色胺的释放是否发生改变。目的探讨精神分裂症患者血清素的体内释放及其与阴性症状的关系。先验假设，精神分裂症患者的额叶皮层血清素释放能力比健康对照组低，这可能与更严重的基线阴性症状有关。设计、环境和参与者这是一项在英国伦敦进行的单中心病例对照神经影像学研究。所有参与者在基线和口服d -安非他明0.5mg/kg后3小时进行动态90分钟[11 C]Cimbi-36正电子发射断层扫描（PET）。数据收集于2015年至2024年。参与者包括患有DSM-5精神分裂症的稳定成年门诊患者（无抗精神病药物或服用抗精神病药物，但对5-羟色胺受体2A [5-HT2A]受体的亲和力可忽略不计）和年龄、性别和体重指数相匹配的健康对照。主要的神经影像学结果是血清素释放能力的组间差异，预先指定为额叶皮质的百分比变化[11 C]基线和d -安非他明扫描之间的Cimbi-36结合电位。结果共纳入54例，其中精神分裂症患者26例（平均[SD]年龄33.3[9.1]岁，男性16例[62%]；未服用抗精神病药物21例[81%]），健康对照28例（平均[SD]年龄32.0[9.5]岁，男性19例[68%]）。精神分裂症患者额叶皮层血清素释放量显著高于健康对照组（18.0%;95% CI, 2.5%-33.6%; P = 0.02; Cohen d = 0.69）。在精神分裂症患者中，额叶皮层5 -羟色胺释放量越大，基线阴性症状越严重（简要阴性症状量表：Pearson r = 0.42; P = 0.04），功能越差（社会功能量表：Pearson r = - 0.42; P = 0.04）。探索性分析显示，与健康对照组相比，以原发性和持续性阴性症状为特征的缺乏性精神分裂症（平均差值= 32.3%；经fdr校正的P值= 0.001;Cohen d = 1.10）和非缺乏性精神分裂症（平均差值= 28.9%；经fdr校正的P值= 0.004;Cohen d = 0.89）的额叶皮层血清素释放显著增加。这些发现在21名没有服用抗精神病药物的精神分裂症患者身上得到了重复。基线皮质[11 C]Cimbi-36结合（索引基线皮质5-HT2A受体水平）在精神分裂症中没有改变。本病例对照研究发现，精神分裂症病理生理中血清素能功能障碍与阴性症状相关，提示调节血清素释放可作为治疗阴性症状的靶点。探索性分析的结果表明，在缺乏性精神分裂症亚组中，血清素功能障碍特别明显。
{"title":"Role of Serotonin in the Neurobiology of Schizophrenia and Association With Negative Symptoms","authors":"Martin Osugo, Thomas Whitehurst, David Erritzoe, Richard Carr, Abhishekh H. Ashok, Lucia Maccioni, Ellis Chika Onwordi, Grazia Rutigliano, Nikola Rahaman, Atheeshaan Arumuham, Antonio de Marvao, Roger N. Gunn, Eugenii A. Rabiner, Tiago Reis Marques, Mattia Veronese, Oliver D. Howes","doi":"10.1001/jamapsychiatry.2025.3430","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.3430","url":null,"abstract":"Importance The involvement of the serotonin system in the pathophysiology of schizophrenia has been proposed for over 60 years, but there has been no prior study to test if there is altered serotonin release in vivo in schizophrenia (to the authors’ knowledge). Objective To investigate serotonin release in vivo in schizophrenia and its association with negative symptoms. It was hypothesized a priori that frontal cortex serotonin release capacity would be lower in schizophrenia compared with healthy controls and that this would be associated with more severe baseline negative symptoms. Design, Setting, and Participants This was a single-center case-control neuroimaging study conducted in London, UK. All participants had dynamic 90-minute [ <jats:sup>11</jats:sup> C]Cimbi-36 positron emission tomography (PET) scans at baseline and 3 hours after oral administration of <jats:sc>d</jats:sc> -amphetamine 0.5mg/kg. Data were collected between 2015 and 2024. Participants included stable adult outpatients with <jats:italic toggle=\"yes\">DSM-5</jats:italic> schizophrenia (antipsychotic free or taking antipsychotics with negligible affinity for 5-hydroxytryptamine receptor 2A [5-HT2A] receptors) and healthy controls matched for age, sex, and body mass index. Main Outcomes and Measures The primary neuroimaging outcome was the group difference in serotonin release capacity, prespecified as the percentage change in frontal cortex [ <jats:sup>11</jats:sup> C]Cimbi-36 binding potential between the baseline and <jats:sc>d</jats:sc> -amphetamine scans. Results A total of 54 individuals were included, 26 with <jats:italic toggle=\"yes\">DSM-5</jats:italic> schizophrenia (mean [SD] age, 33.3 [9.1] years, 16 male [62%]; 21 not taking antipsychotic medication [81%]) and 28 healthy controls (mean [SD] age, 32.0 [9.5] years, 19 male [68%]). Frontal cortex serotonin release was significantly greater in the group with schizophrenia compared with healthy controls (18.0%; 95% CI, 2.5%-33.6%; <jats:italic toggle=\"yes\">P</jats:italic> = .02; Cohen <jats:italic toggle=\"yes\">d</jats:italic> = 0.69). In schizophrenia, greater frontal cortex serotonin release was correlated with more severe baseline negative symptoms (Brief Negative Symptom Scale: Pearson <jats:italic toggle=\"yes\">r</jats:italic> = 0.42; <jats:italic toggle=\"yes\">P</jats:italic> = .04) and poorer functioning (Social Functioning Scale: Pearson <jats:italic toggle=\"yes\">r</jats:italic> = −0.42; <jats:italic toggle=\"yes\">P</jats:italic> = .04). Exploratory analyses showed significantly greater frontal cortex serotonin release in deficit schizophrenia, characterized by primary and enduring negative symptoms, compared with healthy controls (mean difference = 32.3%; FDR-corrected <jats:italic toggle=\"yes\">P</jats:italic> value = 0.001; Cohen <jats:italic toggle=\"yes\">d</jats:italic> = 1.10) and nondeficit schizophrenia (mean difference = 28.9%; FDR-corrected <jats:italic toggle=\"yes\">P</jats:italic> value = 0.004; Cohen <","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"6 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717560","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 : 2025-12-10DOI: 10.1001/jamapsychiatry.2025.3727
Andrew Aballa,Dorcas G Mwigereri,Zhuo Zhao,Willie Njoroge,Linda Khakali,Rachel Maina,David Andai,James Orwa,Amos Bunde,Eileen M Weinheimer-Haus,Jessica Baker,Lukoye Atwoli,Srijan Sen,Akbar K Waljee,Anthony K Ngugi,Amina Abubakar,Zhenke Wu,Zul Merali,Elena Frank
{"title":"Depressive Symptoms and Associated Factors Among Kenyan Health Care Workers.","authors":"Andrew Aballa,Dorcas G Mwigereri,Zhuo Zhao,Willie Njoroge,Linda Khakali,Rachel Maina,David Andai,James Orwa,Amos Bunde,Eileen M Weinheimer-Haus,Jessica Baker,Lukoye Atwoli,Srijan Sen,Akbar K Waljee,Anthony K Ngugi,Amina Abubakar,Zhenke Wu,Zul Merali,Elena Frank","doi":"10.1001/jamapsychiatry.2025.3727","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2025.3727","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"10 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145711115","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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