ArticleTranslational psychiatry2020
A polygenic predictor of treatment-resistant depression using whole exome sequencing and genome-wide genotyping.
Article in Translational psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 49 citations in OpenAlex.
- Genome-wide association meta-analysis and rare copy number variant analysis of treatment-resistant depression.Molecular psychiatry · 2025Pooled it
- Comprehensive Characterization of Antidepressant Pharmacogenetics: A Systematic Review of Studies in Major Depressive Disorder.Clinical and translational science · 2025Pooled it
- Comparative polygenic predispositions of treatment-resistant depression in East Asian and European populations.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Association of psychosocial factors and biological pathways identified from rare-variant analysis with longitudinal trajectories of treatment response in major depressive disorder.BMC psychiatry · 2025Article
- Treatment-resistant depression: role of genetic factors in the perspective of clinical stratification and treatment personalisation.Molecular psychiatry · 2025Review
- The genetics of severe depression.Molecular psychiatry · 2025Review
- Perspectives in treatment-resistant depression: esketamine and electroconvulsive therapy.Wiener klinische Wochenschrift · 2025Review
- Genetic Correlates of Treatment-Resistant Depression.JAMA psychiatry · 2025Article
- Pharmaco-Multiomics: A New Frontier in Precision Psychiatry.International journal of molecular sciences · 2025Review
- Review
- Exome functional risk score and brain connectivity can predict social adaptability outcome of children with autism spectrum disorder in 4 years' follow up.Frontiers in psychiatry · 2024Article
- Organic cation transporter 2 contributes to SSRI antidepressant efficacy by controlling tryptophan availability in the brain.Translational psychiatry · 2023Article
- Exome-wide association study of treatment-resistant depression suggests novel treatment targets.Scientific reports · 2023Article
- Observational
- Genetics in psychiatry: Methods, clinical applications and future perspectives.PCN reports : psychiatry and clinical neurosciences · 2022Review
- Different responses to risperidone treatment in Schizophrenia: a multicenter genome-wide association and whole exome sequencing joint study.Translational psychiatry · 2022Article
- Precision medicine in mood disorders.PCN reports : psychiatry and clinical neurosciences · 2022Review
- Lost in translation. The quest for definitions of treatment-resistant depression with a focus on inflammation-related gene expression.Brain, behavior, & immunity - health · 2021Article
- Biobank Scale Pharmacogenomics Informs the Genetic Underpinnings of Simvastatin Use.Clinical pharmacology and therapeutics · 2021Article
- Transcriptome-wide association study of treatment-resistant depression and depression subtypes for drug repurposing.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
Corrections and comments
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Authors and funding
14 authors at 9 institutions in 7 countries.
Funding
Abstract
Treatment-resistant depression (TRD) occurs in ~30% of patients with major depressive disorder (MDD) but the genetics of TRD was previously poorly investigated. Whole exome sequencing and genome-wide genotyping were available in 1209 MDD patients after quality control. Antidepressant response was compared to non-response to one treatment and non-response to two or more treatments (TRD). Differences in the risk of carrying damaging variants were tested. A score expressing the burden of variants in genes and pathways was calculated weighting each variant for its functional (Eigen) score and frequency. Gene-based and pathway-based scores were used to develop predictive models of TRD and non-response using gradient boosting in 70% of the sample (training) which were tested in the remaining 30% (testing), evaluating also the addition of clinical predictors. Independent replication was tested in STAR*D and GENDEP using exome array-based data. TRD and non-responders did not show higher risk to carry damaging variants compared to responders. Genes/pathways associated with TRD included those modulating cell survival and proliferation, neurodegeneration, and immune response. Genetic models showed significant prediction of TRD vs. response and they were improved by the addition of clinical predictors, but they were not significantly better than clinical predictors alone. Replication results were driven by clinical factors, except for a model developed in subjects treated with serotonergic antidepressants, which showed a clear improvement in prediction at the extremes of the genetic score distribution in STAR*D. These results suggested relevant biological mechanisms implicated in TRD and a new methodological approach to the prediction of TRD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.