Genetic susceptibility for major depressive disorder associates with trajectories of depressive symptoms across childhood and adolescence

Abstract

Background: Depression that onsets during childhood and adolescence is associated with worse illness course and outcomes. However, the genetic factors that influence risk for early-onset depression remain mostly unknown. Using data collected over thirteen years, we examined whether polygenic risk scores (PRS) capturing genetic risk for major depressive disorder (MDD) were associated with early-onset depressive symptoms, as assessed from childhood to adolescence. Methods: Data came from the Avon Longitudinal Study of Parents and Children, a prospective, longitudinal birth cohort (analytic sample=7,308 youth). We analyzed the relationship between genetic susceptibility to depression and three time-dependent measures of depressive symptoms across ages 4-16.5 (trajectories, onset, and cumulative burden of symptoms). Trajectories were constructed using a growth mixture model with structured residuals. Symptom onset and cumulative burden were assessed using the intercept and area under the trajectory curves, respectively. PRS were generated using MDD summary statistics from the Psychiatric Genomics Consortium. We used MAGMA to identify gene-level associations with these measures. Results: Youth were classified into six classes of depressive symptom trajectories: high/renitent (26.5% of youth), high/reversing (5.8%), childhood decrease (6.1%), late childhood peak (3%), adolescent spike (2.5%), and minimal symptoms (56.1%). PRS could discriminate between youth in the "high" classes compared to the minimal symptoms and childhood decrease classes. Two genes (SIX5; DMPK) were nominally associated with both onset and cumulative burden. Conclusions: This study highlights a role for genetic factors in shaping depressive symptoms across childhood and adolescence, particularly among youths with generally high or low symptoms, regardless of age-independent responding.

Genetic susceptibility for major depressive disorder associates with trajectories of depressive symptoms across childhood and adolescence

“…Major depressive disorder (MDD) is one of the most common, costly, and disabling mental disorders, with lifetime prevalence estimated at 11.7% among adolescents (Merikangas et al, 2010) and 16.6% among adults in the United States (Kessler et al, 2005). Whereas depression can emerge at any point in the life course, nearly one third of those who have depression report a first onset before age 21 (Zisook et al, 2007).…”

Depression polygenic scores are associated with major depressive disorder diagnosis and depressive episode in Mexican adolescents

“…Extant work has indicated that depression PRS were associated with childhood-persistent depression and early-adult onset depression in a predominantly European-ancestry sample (Kwong et al, 2019). Other work has shown that a depression PRS was associated with increasing and high depressive symptoms across childhood and adolescence (Lussier et al, 2020) and a steep increase in depressive symptoms in adolescence and young adulthood (Kwong et al, 2020) in Europeanancestry samples. Additional research has indicated that in a European-ancestry sample, depression PRS were associated with late adolescent depression, but not low or early-onset adolescent depression (Rice et al, 2019).…”