ArticleJAMA psychiatry2025
Genetic Correlates of Treatment-Resistant Depression.
Article in JAMA psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
6 citing papers in PubMed.
- Comparative polygenic predispositions of treatment-resistant depression in East Asian and European populations.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- The relevance of phenotypic definition in treatment resistant forms of major depressive disorder: a narrative review.Frontiers in pharmacology · 2026Review
- Closed-loop neuromodulation: a paradigm shift in precision neuroscience for clinical and cognitive applications.Frontiers in neuroscience · 2026Review
- Reshaping Precision Cancer Pain Management with Multimodal Artificial Intelligence: A Review on Subtyping and Treatment Response Prediction.Journal of pain research · 2026Review
- Treatment resistant depression: Socio-demographic characteristics, comorbidity and treatment patterns from the All of Us Research Program.Journal of affective disorders · 2025Article
- Polygenic scores and antidepressant treatment outcomes in major depression: a critical integrative review.Neuroscience applied · 2025Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Importance: Treatment-resistant depression (TRD) is a major challenge in mental health, affecting a significant number of patients and leading to considerable burdens. The etiological factors contributing to TRD are complex and not fully understood. Objective: To investigate the genetic factors associated with TRD using polygenic scores (PGS) across various traits and explore their potential role in the etiology of TRD using large-scale genomic data from the All of Us (AoU) Research Program. Design, Setting, and Participants: This study was a cohort design with observational data from participants in the AoU Research Program who have both electronic health records and genomic data. Data analysis was performed from March 27 to October 24, 2024. Exposures: PGS for 61 unique traits from 7 domains. Main Outcomes and Measures: Logistic regressions to test if PGS was associated with treatment-resistant depression (TRD) compared with treatment-responsive major depressive disorder (trMDD). Cox proportional hazard model was used to determine if the progressions from MDD to TRD were associated with PGS. Results: A total of 292 663 participants (median [IQR] age, 57 (41-69) years; 175 981 female [60.1%]) from the AoU Research Program were included in this analysis. In the discovery set (124 945 participants), 11 of the selected PGS were found to have stronger associations with TRD than with trMDD, encompassing PGS from domains in education, cognition, personality, sleep, and temperament. Genetic predisposition for insomnia (odds ratio [OR], 1.11; 95% CI, 1.07-1.15) and specific neuroticism (OR, 1.11; 95% CI, 1.07-1.16) traits were associated with increased TRD risk, whereas higher education (OR, 0.88; 95% CI, 0.85-0.91) and intelligence (OR, 0.91; 95% CI, 0.88-0.94) scores were protective. The associations held across different TRD definitions (meta-analytic R2 >83%) and were consistent across 2 other independent sets within AoU (the whole-genome sequencing Diversity dataset, 104 388, and Microarray dataset, 63 330). Among 28 964 individuals followed up over time, 3854 developed TRD within a mean of 944 days (95% CI, 883-992 days). All 11 previously identified and replicated PGS were found to be modulating the conversion rate from MDD to TRD. Conclusions and Relevance: Results of this cohort study suggest that genetic predisposition related to neuroticism, cognitive function, and sleep patterns had a significant association with the development of TRD. These findings underscore the importance of considering psychosocial factors in managing and treating TRD. Future research should focus on integrating genetic data with clinical outcomes to enhance understanding of pathways leading to treatment resistance.
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Registered trials
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