The death(s) of close friends and family moderate genetic influences on symptoms of major depressive disorder in adolescents

Abstract

Background Prior work has suggested that genetic influences on Major Depressive Disorder (MDD) may be activated by the experience of negative life events. However, it is unclear whether these results persist when controlling for the possibility of confounding active gene-environment correlations (rGE). Methods We examined a sample of 1,230 adopted and biological siblings between the ages of 10 to 20 years from the Sibling Interaction and Behavior Study (SIBS). MDD was measured via a lifetime DSM-IV symptom count. Number of deaths experienced served as our environmental risk experience. Because this variable is largely independent of the individual's choices/behaviors, we were able to examine GxE while circumventing possible rGE confounds. Results Biometric analyses revealed pronounced linear increases in the magnitude of genetic influences on symptoms of MDD with the number of deaths experienced, such that genetic influences were estimated to be near-zero for those who had experienced no deaths but were quite large in those who had experienced two or more deaths (i.e., accounting for roughly two-thirds of the phenotypic variance). By contrast, shared and non-shared environmental influences on symptoms of MDD were not meaningfully moderated by number of deaths experienced. Conclusions Such results constructively replicate prior findings of genetic moderation of depressive symptoms by negative life events, thereby suggesting that this effect is not a function of active rGE confounds. Our findings are thus consistent with the notion that exposure to specific negative life events may serve to activate genetic risk for depression during adolescence.

The effects of the interplay of genetics and early environmental risk on the course of internalizing symptoms from late childhood through adolescence

“…More specifically, the per month probability of MDD among monozygotic twins concordant for MDD and who had experienced a "severe" life event was more than twice that of monozygotic twins discordant for MDD. Similarly, within the context of a sample of adopted and biological children, Gheyara, Klump, McGue, Iacono, and Burt (2011) reported a GeneÂEnvironment interaction in terms of the risk of MDD, such that the effect of friends' and family deaths on the risk of lifetime MDD was moderated by genetic influences. Caspi et al (2003) likely represents one of the earliest and most referenced example of a specific Gene  Environment interaction in the development of depression.…”

Comorbid alcohol and mental health disorders: a longitudinal analysis of development to young adulthood

“…It has been suggested that exposure to major negative life events can activate genetic risks for child and adolescent depression (182).…”