Association of Familial Aggregation of Major Depression With Risk of Major Depression

IMPORTANCE: Major depression (MD) aggregates within families, but how family history of MD confers risk of MD over the life course is unclear. Such knowledge is important to identify and prevent possible depressogenic effects of family environment. OBJECTIVE: To examine the association between family MD history and risk of MD including association with age, sex, type of kinship, and age of the affected family member. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included all Danish citizens born from 1960 to 2003 with known parental identity followed up from their 15th birthday until time of MD, censoring, or December 31, 2018. Analysis took place between April 2022 and December 2022. EXPOSURES: Family members with first-time MD using International Classification of Diseases, Eighth Revision codes 296.09, 296.29, 298.09, and 300.49 or 10th Revision codes F32.0-F33.9, family members’ age at MD onset, and individuals’ age at exposure to family MD MAIN OUTCOMES AND MEASURES: Multivariable Poisson regression was applied to estimate the incidence rate ratio (IRR) with 95% CI of first-time MD. RESULTS: Of 2 903 430 individuals (1 486 574 [51.2%] men), 37 970 men (2.6%) and 70 223 women (5.0%) developed MD during follow-up. For men, exposure to maternal, paternal, or full sibling MD were associated with a 2-times higher risk of MD (IRR, 2.10 [95% CI, 2.02-2.19]; IRR, 2.04 [95% CI, 1.94-2.14]; IRR, 2.08 [95% CI, 1.97-2.19]) and the associated risk increased with number of affected family members. This pattern was similar for women. For men, family members’ age at MD onset was not associated with MD. For women, maternal MD onset at 69 years or younger was associated with higher IRRs of MD (age