JAMA Psychiatry最新文献

{"title":"Mapping Lesions That Cause Psychosis to a Human Brain Circuit and Proposed Stimulation Target","authors":"Andrew R. Pines, Summer B. Frandsen, William Drew, Garance M. Meyer, Calvin Howard, Stephan T. Palm, Frederic L. W. V. J. Schaper, Christopher Lin, Konstantin Butenko, Michael A. Ferguson, Maximilian U. Friedrich, Jordan H. Grafman, Ari D. Kappel, Clemens Neudorfer, Natalia S. Rost, Lauren L. Sanderson, Joseph J. Taylor, Ona Wu, Isaiah Kletenik, Jacob W. Vogel, Alexander L. Cohen, Andreas Horn, Michael D. Fox, David Silbersweig, Shan H. Siddiqi","doi":"10.1001/jamapsychiatry.2024.4534","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.4534","url":null,"abstract":"ImportanceIdentifying anatomy causally involved in psychosis could inform therapeutic neuromodulation targets for schizophrenia.ObjectiveTo assess whether lesions that cause secondary psychosis have functional connections to a common brain circuit.Design, Setting, and ParticipantsThis case-control study mapped functional connections of published cases of lesions causing secondary psychosis compared with control lesions unassociated with psychosis. Published cases of lesion-induced psychosis were analyzed in a computational laboratory. Participants had documented brain lesions associated with new-onset psychotic symptoms without a history of psychosis. Control cases included 1156 patients with lesions not associated with psychosis. Generalizability across lesional datasets was assessed using an independent cohort of 181 patients with brain lesions who subsequently underwent neurobehavioral testing. Data were analyzed from June 2022 to April 2024.ExposuresLesions causing secondary psychosis.Main Outcomes and MeasuresPsychosis or no psychosis.ResultsA total of 153 lesions from published cases were determined to be causal of psychosis, 42 of which were described as schizophrenia or schizophrenia-like (71 [46%] patients were male, 82 [54%] female; mean [SD] age, 50.0 [20.8] years). Lesions that caused secondary psychosis mapped to a common brain circuit defined by functional connectivity to the posterior subiculum of the hippocampus (84% functional overlap, family-wise error [FWE] rate corrected <jats:italic>P</jats:italic> < 5 × 10<jats:sup>−5</jats:sup>). At a lower statistical threshold (>75% overlap, FWE-corrected <jats:italic>P</jats:italic> < 5 × 10<jats:sup>−4</jats:sup>), this circuit included the ventral tegmental area, retrosplenial cortex, lobule IX and dentate nucleus of the cerebellum, and the mediodorsal and midline nuclei of the thalamus. This circuit was consistent when derived from schizophrenia-like cases (spatial <jats:italic>r</jats:italic> = 0.98). We repeated these analyses after excluding lesions intersecting the hippocampus (n = 47) and found a consistent functional connectivity profile (spatial <jats:italic>r</jats:italic> = 0.98) with the posterior subiculum remaining the center of connectivity (>75% overlap, FWE-corrected <jats:italic>P</jats:italic> < 5 × 10<jats:sup>−5</jats:sup>), demonstrating a circuit-level effect. In an independent observational cohort of patients with penetrating head trauma (n = 181), lesions associated with symptoms of psychosis exhibited significantly similar connectivity profiles to the lesion-derived psychosis circuit (suspiciousness, <jats:italic>P</jats:italic> = .03; unusual thought content, <jats:italic>P</jats:italic> = .046). Voxels in the rostromedial prefrontal cortex are highly correlated with this psychosis circuit (spatial <jats:italic>r</jats:italic> = 0.82), suggesting the rostromedial prefrontal cortex as a promising transcrani","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"18 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393150","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}

{"title":"Making Progress in Clinical Trials for Suicide Prevention","authors":"Samuel T. Wilkinson, Craig J. Bryan, Larry D. Alphs, Carla M. Canuso, Michael J. Ostacher, Rebecca B. Price, Michael H. Bloch, Carlos A. Zarate, Taeho Greg Rhee","doi":"10.1001/jamapsychiatry.2024.4810","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.4810","url":null,"abstract":"ImportanceSuicide is a public health crisis, and despite renewed efforts to confront this problem, suicide rates continue to rise in the US. While suicide prevention encompasses a broad array of strategies, treatment development is lagging. Within this realm, clinical trials are the criterion standard for evaluating safety and efficacy of new treatments.ObservationsMost clinical trials conducted among patients with mental illness have excluded patients at risk of suicide. Historical reasons for this include regulatory challenges, liability concerns, ethical questions, discomfort working directly with high-risk patients, and the belief that research is too risky for individuals at elevated risk for suicide.Conclusions and RelevanceSeveral considerations are provided for investigators in the design of trials targeting at-risk populations, including thoughtful selection of study outcome, use of time-to-event design and analysis (which may simultaneously satisfy ethical concerns and scientific aims), enrolling an enriched sample (eg, among patients recently discharged from the hospital), and provision of usual care in the comparator group. Caution should be exercised to avoid excessive or unreasonable safety requirements, which may lead participants to minimize self-report of suicidal ideation or to drop out of trials. Where possible, regulatory bodies (institutional review boards [IRBs] and data and safety monitoring boards) should consult with or include as members those with direct clinical experience with this high-risk population. An important ethical principle for IRB members and other regulators to consider is that suicide-related events are expected in this clinical population.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"30 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393148","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}

{"title":"Integrated Nicotine Replacement and Behavioral Support to Reduce Smoking in Opioid Agonist Therapy","authors":"Karl Trygve Druckrey-Fiskaaen, Tesfaye Madebo, Jan Tore Daltveit, Jørn Henrik Vold, Einar Furulund, Fatemeh Chalabianloo, Torgeir Gilje Lid, Lars Thore Fadnes","doi":"10.1001/jamapsychiatry.2024.4801","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.4801","url":null,"abstract":"ImportanceApproximately 85% of individuals receiving opioid agonist therapy for opioid dependence smoke tobacco. Despite the significant health risks associated with smoking-related diseases, there has been limited evaluation of smoking interventions tailored to this population.ObjectiveTo determine the effectiveness of an intervention combining nicotine replacement with brief behavioral support in reducing cigarette use.Design, Setting, and ParticipantsThis multicenter randomized clinical trial was conducted from April 2022 to October 2023 in 7 specialized opioid agonist therapy clinics in Bergen and Stavanger, Norway. The analyst was blinded to patient groupings. Assessors (study nurses) were not fully blinded to participant allocation. Individuals diagnosed with opioid dependency receiving opioid agonist therapy at participating clinics and smoking at least 1 cigarette per day were eligible for participation. Data analysis was performed from December 2023 through October 2024.InterventionIn addition to standard opioid agonist therapy, participants in the intervention group received a 16-week integrated treatment combining nicotine replacement with brief behavioral support. Participants in the control group received only standard opioid agonist therapy.Main Outcomes and MeasuresThe primary outcome was at least a 50% reduction in the number of cigarettes smoked, self-reported as cigarette use in the past 7 days at week 16. The analysis followed intention-to-treat principles. Cigarette use was self-reported as per the timeline-follow-back method.ResultsAmong the 259 participants (mean [SD] age, 48.5 [10.4] years; 80 [30.9%] female), 135 were allocated to the intervention group and 124 to the control group. The odds ratio of at least halving the number of cigarettes smoked was 2.07 (95% CI, 1.14-3.75) in the intervention group compared with the control group.Conclusions and RelevanceProviding integrated nicotine replacement and behavioral support at opioid agonist treatment clinics effectively helped opioid-dependent participants reduce the number of cigarettes smoked.Trial RegistrationClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"https://clinicaltrials.gov/study/NCT05290025\">NCT05290025</jats:ext-link>","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"15 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393146","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}

{"title":"Once-Weekly Semaglutide in Adults With Alcohol Use Disorder","authors":"Christian S. Hendershot, Michael P. Bremmer, Michael B. Paladino, Georgios Kostantinis, Thomas A. Gilmore, Neil R. Sullivan, Amanda C. Tow, Sarah S. Dermody, Mark A. Prince, Robyn Jordan, Sherry A. McKee, Paul J. Fletcher, Eric D. Claus, Klara R. Klein","doi":"10.1001/jamapsychiatry.2024.4789","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.4789","url":null,"abstract":"ImportancePreclinical, observational, and pharmacoepidemiology evidence indicates that glucagon-like peptide 1 receptor agonists (GLP-1RAs) may reduce alcohol intake. Randomized trials are needed to determine the clinical significance of these findings.ObjectiveTo evaluate the effects of once-weekly subcutaneous semaglutide on alcohol consumption and craving in adults with alcohol use disorder (AUD).Design, Setting, and ParticipantsThis was a phase 2, double-blind, randomized, parallel-arm trial involving 9 weeks of outpatient treatment. Enrollment occurred at an academic medical center in the US from September 2022 to February 2024. Of 504 potential participants assessed, 48 non–treatment-seeking participants with AUD were randomized.InterventionParticipants received semaglutide (0.25 mg/week for 4 weeks, 0.5 mg/week for 4 weeks, and 1.0 mg for 1 week) or placebo at weekly clinic visits.Main Outcomes and MeasuresThe primary outcome was laboratory alcohol self-administration, measured at pretreatment and posttreatment (0.5 mg/week). Secondary and exploratory outcomes, including prospective changes in alcohol consumption and craving, were assessed at outpatient visits.ResultsForty-eight participants (34 [71%] female; mean [SD] age, 39.9 [10.6] years) were randomized. Low-dose semaglutide reduced the amount of alcohol consumed during a posttreatment laboratory self-administration task, with evidence of medium to large effect sizes for grams of alcohol consumed (β, −0.48; 95% CI, −0.85 to −0.11; <jats:italic>P</jats:italic> = .01) and peak breath alcohol concentration (β, −0.46; 95% CI, −0.87 to −0.06; <jats:italic>P</jats:italic> = .03). Semaglutide treatment did not affect average drinks per calendar day or number of drinking days, but significantly reduced drinks per drinking day (β, −0.41; 95% CI, −0.73 to −0.09; <jats:italic>P</jats:italic> = .04) and weekly alcohol craving (β, −0.39; 95% CI, −0.73 to −0.06; <jats:italic>P</jats:italic> = .01), also predicting greater reductions in heavy drinking over time relative to placebo (β, 0.84; 95% CI, 0.71 to 0.99; <jats:italic>P</jats:italic> = .04). A significant treatment-by-time interaction indicated that semaglutide treatment predicted greater relative reductions in cigarettes per day in a subsample of individuals with current cigarette use (β, −0.10; 95% CI, −0.16 to −0.03; <jats:italic>P</jats:italic> = .005).Conclusions and RelevanceThese findings provide initial prospective evidence that low-dose semaglutide can reduce craving and some drinking outcomes, justifying larger clinical trials to evaluate GLP-1RAs for alcohol use disorder.Trial RegistrationClinicalTrials.gov Identifier: <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"https://clinicaltrials.gov/study/NCT05520775?tab=results\">NCT05520775</jats:ext-link>","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"5 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393149","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}

{"title":"An Opportunity to Advance Cannabis Science—DEA Rescheduling","authors":"Kevin P. Hill, Anshul V. Puli","doi":"10.1001/jamapsychiatry.2024.4691","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.4691","url":null,"abstract":"This Viewpoint discusses the regulatory and financial barriers to cannabis research, and the potential changes to these barriers if cannabis is reclassified as a Schedule III drug.","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"8 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143125204","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}

{"title":"Observational and Genetic Analyses of Traumatic Experiences and Endometriosis","authors":"Dora Koller, Solveig Løkhammer, Oksana Goroshchuk, Veronika Denner, Brendan Stiltner, Marina Mitjans, Jun He, Hugh S. Taylor, Rebecca B. Lawn, Karestan C. Koenen, Renato Polimanti","doi":"10.1001/jamapsychiatry.2024.4694","DOIUrl":"https://doi.org/10.1001/jamapsychiatry.2024.4694","url":null,"abstract":"ImportanceAlthough psychological traumas have been associated with endometriosis, limited information is available regarding the role of trauma type and genetic predisposition.ObjectiveTo examine the relationship between traumatic experiences and endometriosis using observational and genetically informed analyses.Design, Setting, and ParticipantsFor this case-control study, the analyses were performed between May 13, 2023, and September 30, 2024. Genotypic and phenotypic information was combined from UK Biobank individual-level data (up to 8276 patients with endometriosis and 240 117 female controls) with genome-wide information available from a large meta-analysis (European ancestry: 21 779 patients and 449 087 female controls; East Asian ancestry: 1713 patients and 1581 female controls) and the FinnGen cohort (16 588 patients and 111 583 female controls of European descent).Main Outcomes and MeasuresPhenotypic associations via multiple regression; latent-class analysis (LCA) to investigate the co-occurrence patterns of different traumatic experiences in endometriosis cases and controls; genetic correlation and polygenic risk scoring (PRS) analyses to assess pleiotropy linking traumatic events to endometriosis.ResultsUp to 8276 women with endometriosis (mean [SD] age, 53.2 [13.0] years) and 240 117 female controls (mean [SD] age, 56.5 [9.6] years) were investigated in the study. Women with endometriosis were more likely to report childhood and adulthood traumatic experiences and stressful events (eg, contact trauma odds ratio [OR], 1.28; 95% CI, 1.02-1.26). Our LCA highlighted the association of endometriosis with emotional and physical trauma (225 [8%] vs 3948 [5%]; &lt;jats:italic&gt;P&lt;/jats:italic&gt; &amp;amp;lt; 2.2 × 10&lt;jats:sup&gt;−16&lt;/jats:sup&gt;) and sexual trauma (414 [5%] vs 3158 [4%]; &lt;jats:italic&gt;P&lt;/jats:italic&gt; = 2.9 × 10&lt;jats:sup&gt;−3&lt;/jats:sup&gt;). Unaffected women (controls) were more likely assigned to the “no trauma” latent class (563 [20%] vs 18 949 [24%]; &lt;jats:italic&gt;P&lt;/jats:italic&gt; = 7.4 × 10&lt;jats:sup&gt;−14&lt;/jats:sup&gt;). Our genetic correlation (rg) analyses linked endometriosis to multiple trauma-related outcomes, including posttraumatic stress disorder (meta-analysis rg = 0.31, &lt;jats:italic&gt;P&lt;/jats:italic&gt; = 7.1 × 10&lt;jats:sup&gt;−16&lt;/jats:sup&gt;; FinnGen rg = 0.26, &lt;jats:italic&gt;P&lt;/jats:italic&gt; = 4.7 × 10&lt;jats:sup&gt;−15&lt;/jats:sup&gt;) and childhood maltreatment (meta-analysis rg = 0.23, &lt;jats:italic&gt;P&lt;/jats:italic&gt; = 1.3 × 10&lt;jats:sup&gt;−6&lt;/jats:sup&gt;; FinnGen rg = 0.16, &lt;jats:italic&gt;P&lt;/jats:italic&gt; = 1 × 10&lt;jats:sup&gt;−4&lt;/jats:sup&gt;). Endometriosis PRS was associated with increased odds of the disease (β = 0.31, &lt;jats:italic&gt;P&lt;/jats:italic&gt; &amp;amp;lt; 2.2 × 10&lt;jats:sup&gt;−16&lt;/jats:sup&gt;), but no interaction was observed with different types of trauma events.Conclusions and RelevanceThe present study comprehensively investigated the impact of childhood and adulthood traumatic experiences and stressful events on endometriosis. In particular, our findings highl","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":"61 1","pages":""},"PeriodicalIF":25.8,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143125203","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}

{"title":"Mental Health Disorder Trends in Denmark According to Age, Calendar Period, and Birth Cohort.","authors":"Natalie C Momen, Christoffer Beck, Mette Lise Lousdal, Esben Agerbo, John J McGrath, Carsten B Pedersen, Merete Nordentoft, Oleguer Plana-Ripoll","doi":"10.1001/jamapsychiatry.2024.3723","DOIUrl":"10.1001/jamapsychiatry.2024.3723","url":null,"abstract":"<p><strong>Importance: </strong>Research suggests an increase in mental disorder incidence in recent years, but this trend remains unexplained, and there is a lack of large studies based on a representative sample that investigate mental disorders over the full spectrum.</p><p><strong>Objective: </strong>To explore sex- and age-specific incidence of any mental disorder and 19 specific disorders according to birth cohort and calendar period.</p><p><strong>Design, setting, and participants: </strong>This was a population-based cohort study among 5 936 202 individuals aged 1 to 80 years living in Denmark at some point between January 1, 2004, and December 31, 2021. Data were derived from the Danish Civil Registration System and analyzed from February to August 2024.</p><p><strong>Exposures: </strong>Birth cohort (8 categories from 1924 to 2011) and calendar period (six 3-year categories from 2004 to 2021).</p><p><strong>Main outcomes and measures: </strong>Incidence rates of mental disorders from 2004 to 2021 by sex and age, according to birth cohort and calendar period, including the first years of the COVID-19 pandemic, using Danish health register data.</p><p><strong>Results: </strong>The population comprised 2 933 857 female individuals and 3 002 345 male individuals, who were followed up for 83.8 million person-years, with median ages at start and end of follow-up of 30.2 and 46.2 years, respectively. There was an overall mental disorder incidence rate of 55.27 every 10 000 person-years. For diagnoses of any mental disorder, higher incidence rates were observed for more recent birth cohorts and calendar periods in the younger ages. Over older ages, incidence rates did not vary so greatly. An increase was observed in rates of most types of mental disorders, especially among young people, and decreases for other types (eg, substance use disorders). Prominent sex differences were also observed. For example, for schizophrenia, a large increase was seen in incidence rates for female individuals in more recent birth cohorts at younger ages, but no change for male individuals, leading to a higher peak incidence for female individuals than for male individuals in the most recent periods. For personality disorders, a large increase was observed in incidence for female individuals over time and a slight decrease for male individuals.</p><p><strong>Conclusions and relevance: </strong>This comprehensive investigation of mental disorders incidence in Denmark indicates sex- and age-specific patterns according to birth cohorts and calendar periods. While trends may partly be explained by increases in incidence, several other factors may contribute, such as diagnostic practices, health sector capacity, and risk factors for mental disorders.</p>","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":"161-170"},"PeriodicalIF":22.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11603380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142728667","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}

{"title":"Error in Figure.","authors":"","doi":"10.1001/jamapsychiatry.2024.4165","DOIUrl":"10.1001/jamapsychiatry.2024.4165","url":null,"abstract":"","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":"208"},"PeriodicalIF":22.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11800011/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807357","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}

{"title":"Linking Genome-Wide Association Studies to Pharmacological Treatments for Psychiatric Disorders.","authors":"Aurina Arnatkeviciute, Alex Fornito, Janette Tong, Ken Pang, Ben D Fulcher, Mark A Bellgrove","doi":"10.1001/jamapsychiatry.2024.3846","DOIUrl":"10.1001/jamapsychiatry.2024.3846","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Importance: &lt;/strong&gt;Large-scale genome-wide association studies (GWAS) should ideally inform the development of pharmacological treatments, but whether GWAS-identified mechanisms of disease liability correspond to the pathophysiological processes targeted by current pharmacological treatments is unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To investigate whether functional information from a range of open bioinformatics datasets can elucidate the relationship between GWAS-identified genetic variation and the genes targeted by current treatments for psychiatric disorders.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design, setting, and participants: &lt;/strong&gt;Associations between GWAS-identified genetic variation and pharmacological treatment targets were investigated across 4 psychiatric disorders-attention-deficit/hyperactivity disorder, bipolar disorder, schizophrenia, and major depressive disorder. Using a candidate set of 2232 genes listed as targets for all approved treatments in the DrugBank database, each gene was independently assigned 2 scores for each disorder-one based on its involvement as a treatment target and the other based on the mapping between GWAS-implicated single-nucleotide variants (SNVs) and genes according to 1 of 4 bioinformatic data modalities: SNV position, gene distance on the protein-protein interaction (PPI) network, brain expression quantitative trail locus (eQTL), and gene expression patterns across the brain. Study data were analyzed from November 2023 to September 2024.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main outcomes and measures: &lt;/strong&gt;Gene scores for pharmacological treatments and GWAS-implicated genes were compared using a measure of weighted similarity applying a stringent null hypothesis-testing framework that quantified the specificity of the match by comparing identified associations for a particular disorder with a randomly selected set of treatments.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Incorporating information derived from functional bioinformatics data in the form of a PPI network revealed links for bipolar disorder (P permutation [P-perm] = 7 × 10-4; weighted similarity score, empirical [ρ-emp] = 0.1347; mean [SD] weighted similarity score, random [ρ-rand] = 0.0704 [0.0163]); however, the overall correspondence between treatment targets and GWAS-implicated genes in psychiatric disorders rarely exceeded null expectations. Exploratory analysis assessing the overlap between the GWAS-identified genetic architecture and treatment targets across disorders identified that most disorder pairs and mapping methods did not show a significant correspondence.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions and relevance: &lt;/strong&gt;In this bioinformatic study, the relatively low degree of correspondence across modalities suggests that the genetic architecture driving the risk for psychiatric disorders may be distinct from the pathophysiological mechanisms currently used for targeting symptom manifestations through pharmacological treatments. Novel approaches incorporating insig","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":"151-160"},"PeriodicalIF":22.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11800018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807359","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}

{"title":"Capturing the Full Range of Buprenorphine Treatment Response.","authors":"Allen J Bailey, Victoria R Votaw, Roger D Weiss, R Kathryn McHugh","doi":"10.1001/jamapsychiatry.2024.3836","DOIUrl":"10.1001/jamapsychiatry.2024.3836","url":null,"abstract":"<p><strong>Importance: </strong>Reliance on abstinence-based treatment success rules may fail to capture the full continuum of treatment response to buprenorphine plus medical counseling (BUP+MC) for opioid use disorder (OUD).</p><p><strong>Objective: </strong>To describe patterns of reduction in illicit opioid use of patients both labeled as a success and nonsuccess based on an abstinent-based treatment outcome rule.</p><p><strong>Design, setting, and participants: </strong>This study is a secondary data analysis of 4 harmonized randomized clinical trials on BUP+MC for OUD from multiple sites that included 869 patients with OUD. These data were analyzed on April 23, 2024. By week 12, 643 participants of the sample original remained (74%).</p><p><strong>Intervention: </strong>All studies included patients randomized to BUP+MC or BUP plus enhanced MC (eg, delivered with adjunctive cognitive behavioral therapy).</p><p><strong>Main outcomes and measures: </strong>Weekly self-reported days of illicit opioid use through 12 weeks of treatment. Abstinence was confirmed by urine drug screen.</p><p><strong>Results: </strong>This study included 869 adults with OUD aged 18 to 69 (mean, 34.2 [SD, 10.45]) years; 287 patients were female (33%), 52 identified as Black (6%), 70 identified Hispanic (8%), 713 identified as White (82%), and 34 identified as other racial groups (4%). Only 377 patients (43%) would have been labeled a success using an abstinence-based success rule. However, the total sample reported a decrease from a mean baseline rate of illicit opioid use nearly every day (6.21 [SD, 1.50] days per week) to a mean of less than 1 day per week at week 12 (0.54 [SD, 1.28]). Importantly, even those who were labeled as nonsuccessful reported a substantial reduction in opioid use from a mean of 6.29 (SD, 1.42) days per week to 1.51 (SD, 1.76) days per week.</p><p><strong>Conclusion and relevance: </strong>In this study, about half of patients receiving BUP+MC achieved near complete abstinence; however, many more experienced a partial treatment response characterized by a substantial reduction in illicit opioid use that falls short of abstinence. Future studies are needed to characterize how these reductions are associated with functional and long-term outcomes. Dissemination of BUP+MC as part of standard buprenorphine prescribing practices is an essential next step given the robust average response of this intervention.</p>","PeriodicalId":14800,"journal":{"name":"JAMA Psychiatry","volume":" ","pages":"201-203"},"PeriodicalIF":22.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11618630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769031","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}