Sources of parent-offspring resemblance for major depression in a national Swedish extended adoption study

Abstract

Importance: Twin studies have assessed sibling resemblance for major depression (MD) but cannot address sources of resemblance across generations. Objective: To clarify the relative importance of genetic and rearing effects on the parent-offspring resemblance for MD. Design: This Swedish population register-based study examined parents and children from the following 5 family types: intact (2 041 816 offspring), adoptive (14 104 offspring), not-lived-with (NLW) father (116 601 offspring), stepfather (67 826 offspring), and triparental (29 205 offspring). The 5 family types permitted quantification of parent-offspring resemblance for genes plus rearing, genes-only, and rearing-only associations. Treated MD was assessed from national primary care, specialist care, and inpatient registries. Data were collected from January 1, 1960, through December 31, 2016. Exposure: Diagnosis of MD vs no diagnosis in parents. Main Outcomes and Measures: Registration for MD. Results: The study population included 2 269 552 offspring (51.5%male and 48.5%female; median age, 42; range, 26-56 years). The weighted tetrachoric correlations for MD across family types and across mothers and fathers were r = 0.17 (95%CI, 0.16-0.17) for genes plus rearing, r = 0.08 (95%CI, 0.06-0.09) for genes-only, and r = 0.08 (95%CI, 0.07-0.09) for rearing-only parent-child associations. Only the genes plus rearing association differed significantly between mothers (weighted tetrachoric correlation, r = 0.18; 95%CI, 0.18-0.18) and fathers (weighted tetrachoric correlation, r = 0.15; 95%CI, 0.15-0.16). In triparental families, the parent-offspring correlations for MD were estimated at r = 0.19 (95%CI, 0.17-0.22) for mothers in the genes plus rearing association, r = 0.10 (95%CI, 0.07-0.13) for NLWfathers in the genes-only association, and r = 0.08 (95%CI, 0.05-0.11) for stepfathers in the rearing-only association. In adoptive families, the effect of affected biological and affected adoptive parents on adoptee risk for MD was additive. In intact families, parental MD diagnosed by specialists in hospital or outpatient settings and primary care physicians affected equally the risk for MD in offspring. Conclusions and Relevance: The parent-offspring resemblance for treated MD arises from genetic factors and rearing experiences to an approximately equal extent. Both forms of cross-generational transmission act additively on the risk for MD in the offspring.