{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T11:30:57Z","timestamp":1791718257249,"version":"4.3.4"},"reference-count":50,"publisher":"American Medical Association (AMA)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Psychiatry"],"published-print":{"date-parts":[[2024,7,1]]},"abstract":"Importance<\/jats:title>Antidepressant responses and the phenotype of treatment-resistant depression (TRD) are believed to have a genetic basis. Genetic susceptibility between the TRD phenotype and other psychiatric disorders has also been established in previous genetic studies, but population-based cohort studies have not yet provided evidence to support these outcomes.<\/jats:p><\/jats:sec>Objective<\/jats:title>To estimate the TRD susceptibility and the susceptibility between TRD and other psychiatric disorders within families in a nationwide insurance cohort with extremely high coverage and comprehensive health care data.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This cohort study assessed data from the Taiwan national health insurance database across entire population (N\u2009=\u200926\u202f554\u202f001) between January 2003 and December 2017. Data analysis was performed from August 2021 to April 2023. TRD was defined as having experienced at least 3 distinct antidepressant treatments in the current episode, each with adequate dose and duration, based on the prescribing records. Then, we identified the first-degree relatives of individuals with TRD (n\u2009=\u200934\u202f467). A 1:4 comparison group (n\u2009=\u2009137\u202f868) of first-degree relatives of individuals without TRD was arranged for the comparison group, matched by birth year, sex, and kinship.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>Modified Poisson regression analyses were performed and adjusted relative risks (aRRs) and 95% CIs were calculated for the risk of TRD, the risk of other major psychiatric disorders, and different causes of mortality.<\/jats:p><\/jats:sec>Results<\/jats:title>This study included 172\u202f335 participants (88\u202f330 male and 84\u202f005 female; mean [SD] age at beginning of follow-up, 22.9 [18.1] years). First-degree relatives of individuals with TRD had lower incomes, more physical comorbidities, higher suicide mortality, and increased risk of developing TRD (aRR, 9.16; 95% CI, 7.21-11.63) and higher risk of other psychiatric disorders than matched control individuals, including schizophrenia (aRR, 2.36; 95% CI, 2.10-2.65), bipolar disorder (aRR, 3.74; 95% CI, 3.39-4.13), major depressive disorder (aRR, 3.65; 95% CI, 3.44-3.87), attention-deficit\/hyperactivity disorders (aRR, 2.38; 95% CI, 2.20-2.58), autism spectrum disorder (aRR, 2.26; 95% CI, 1.86-2.74), anxiety disorder (aRR, 2.71; 95% CI, 2.59-2.84), and obsessive-compulsive disorder (aRR, 3.14; 95% CI, 2.70-3.66). Sensitivity and subgroup analyses validated the robustness of the findings.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>To our knowledge, this study is the largest and perhaps first nationwide cohort study to demonstrate TRD phenotype transmission across families and coaggregation with other major psychiatric disorders. Patients with a family history of TRD had an increased risk of suicide mortality and tendency toward antidepressant resistance; therefore, more intensive treatments for depressive symptoms might be considered earlier, rather than antidepressant monotherapy.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamapsychiatry.2024.0378","type":"journal-article","created":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T15:08:06Z","timestamp":1712156886000},"page":"663","source":"Crossref","is-referenced-by-count":19,"title":["Susceptibility to Treatment-Resistant Depression Within Families"],"prefix":"10.1001","volume":"81","author":[{"given":"Chih-Ming","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan"},{"name":"Institute of Brain Science, School of Medicine, National Yang-Ming Chiao-Tung University, Taipei, Taiwan"},{"name":"Division of Psychiatry, School of Medicine, National Yang-Ming Chiao-Tung University, 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