{"doi":"10.1176/appi.ajp.20240377","title":"Using Medical Records to Investigate the Genetics of Treatment-Resistant Depression Across Health Care Systems","abstract":"Depression is a psychiatric disorder affecting a large proportion of individuals with major social and economic consequences for families and society.In the last ten years, large-scale studies revolutionized our understanding of depression predisposition.In particular, genomewide association studies (GWAS) of millions of participants uncovered hundreds of loci contributing to the polygenic architecture of depressive disorders and symptoms (1, 2).To achieve the statistical power needed to detect the small effects of individual variants, investigators combined cohorts with diverse characteristics and depression phenotypes derived from different data sources (3).Effects detected in these large-scale GWAS are informative of molecular mechanisms shared across the depression spectrum.However, they may be less informative of specific types of depression (4).This means that more efforts are needed to understand the biology of certain depression outcomes.Among them, treatment resistant depression (TRD) surely represents a priority, because of its major clinical implications.Indeed, a large proportion of depression-affected patients do not respond to multiple sequential antidepressant therapies (12%-55% depending on TRD definition) (5).Dissecting TRD pathogenesis could have important translational implications leading to the identification of biological processes informative of response to antidepressant treatments.In this issue of the American Journal of Psychiatry, Kang and colleagues (6) conducted a TRD GWAS of 154,433 participants across four healthcare systems.This represents a major advance in TRD genetics.So far, a key limitation for TRD studies has been defining the outcome of interest in large cohorts.To overcome this issue, the authors leveraged electronic health records (EHR) to derive TRD probabilistic phenotypes considering electroconvulsive therapy (ECT) as the gold-standard target.Among individuals affected by depression, ECT was demonstrated to be an effective treatment for TRD patients showing rapid improvement","journal":"American Journal of Psychiatry","year":2024,"id":483503,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9398,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":229994,"name":"Renato Polimanti","orcid":"0000-0003-0745-6046","position":0,"is_corresponding":true}],"reference_count":18,"raw_metadata":null,"created_at":"2026-07-19T02:07:33.718973Z","pmid":"38946279","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}