Genetic Predispositions to Insomnia, Neuroticism, Linked With Higher Risk for Treatment-Resistant Depression
A genetic predisposition to traits related to neuroticism, cognitive function, and sleep patterns were significantly associated with the development of treatment-resistant depression (TRD) in a cohort study published in JAMA Psychiatry.
“These findings underscore the importance of considering psychosocial factors in managing and treating TRD,” wrote first author Bohan Xu, PhD, of the Laureate Institute for Brain Research, Tulsa, Oklahoma, and study coauthors.
The study used observational data from 292,663 participants in the All of Us Research Program to investigate predisposing genetic factors among people who develop TRD. Researchers looked at polygenic scores for 61 unique traits across 7 domains for associations with TRD compared with treatment-responsive major depressive disorder (MDD).
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In a discovery set spanning 124,945 participants, 11 polygenic scores showed stronger associations with TRD than with treatment-responsive MDD, according to the study. The scores represented traits in the domains of education, cognition, personality, sleep, and temperament.
Genetic predispositions for insomnia and specific neuroticism were linked with an increased risk of TRD. Researchers reported an odds ratio of 1.11 for each. In contrast, genetic predispositions for higher education and intelligence were protective against TRD, with odds ratios of 0.88 and 0.91, respectively.
The association patterns were consistent across different definitions of TRD and 2 independent data sets from the All of Us Research Program that encompassed a total 167,718 participants.
Among 28,964 people with follow up, 3854 developed TRD over an average 944 days, the study found. All 11 previously identified polygenic risk scores modulated the conversion from MDD to TRD.
“Future research should focus on integrating genetic data with clinical outcomes,” researchers wrote, “to enhance understanding of pathways leading to treatment resistance.”
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