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

BACKGROUND: Early-onset depression during childhood and adolescence is associated with a worse course of illness and outcome than adult onset. However, the genetic factors that influence risk for early-onset depression remain mostly unknown. Using data collected over 13 years, we examined whether polygenic risk scores (PRS) that capture genetic risk for depression were associated with depressive symptom trajectories 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 trajectories spanning 4-16.5 years of age (class, onset, and cumulative burden). Trajectories were constructed using a growth mixture model with structured residuals. PRS were generated from the summary statistics of a genome-wide association study of depression risk using data from the Psychiatric Genomics Consortium, UK Biobank, and 23andMe, Inc. We used MAGMA to identify gene-level associations with these measures. RESULTS: Youth were classified into six classes of depressive symptom trajectories: high/renitent (27.9% of youth), high/reversing (9.1%), childhood decrease (7.3%), late childhood peak (3.3%), adolescent spike (2.5%), and minimal symptoms (49.9%). PRS discriminated between youth in the late childhood peak, high/reversing, and high/renitent classes compared to the minimal symptoms and childhood decrease classes. No significant associations were detected at the gene level. CONCLUSIONS: This study highlights differences in polygenic loading for depressive symptoms across childhood and adolescence, particularly among youths with high symptoms in early adolescence, regardless of age-independent patterns.