Polygenic Risk for Depression is Associated with the Severity and Rate of Change in Depressive Symptoms Across Adolescence

Abstract

Adolescence marks a period where depression will commonly onset and previous research using twin studies has suggested that genetic influences play a role in how depression develops and changes across adolescence. Recent genome-wide association studies have also shown that common genetic variants − which can be combined into a polygenic risk score (PRS) − are also implicated in depression. However, the role of PRS in adolescent depression and changes in adolescent depression is not yet understood. We aimed to examine the association between a PRS for depressive symptoms and depressive symptoms across adolescence and young adulthood, and how polygenic risk is associated with changes in depressive symptoms using two methods: cross-sectional analysis and multilevel growth curve modelling to examine the rate of change over time. Using data from over 6000 participants of the Avon Longitudinal Study of Parents and Children (ALSPAC) we examined associations between genetic liability to depressive symptoms (PRS for depressive symptoms) and self-reported depressive symptoms (short mood and feelings questionnaire over 9 occasions from 10-24 years). We examined cross-sectional associations at each age and longitudinal trajectories of depressive symptoms in a repeated measures framework using growth curve analysis. The PRS was associated with depressive symptoms throughout adolescence and young adulthood in cross-sectional and growth curve analyses, though associations were stronger in the latter analyses. Growth curve analyses also provided additional insights, demonstrating that individuals with a higher PRS had steeper trajectories of depressive symptoms across adolescence with a greater increasing rate of change. These results show that common genetics variants as indexed by a PRS for depressive symptoms influence both the severity and rate of change in adolescent depressive symptoms. Longitudinal data that make use of repeated measures designs have the potential to provide greater insights into the factors that influence the onset and persistence of adolescent depression.

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

“…We observed significant positive associations between depression PRS and phenotypic depression. This finding is consistent with previous work linking higher polygenic loading for MDD with elevated depressive symptoms during adolescence in European-ancestry populations (Kwong et al, 2019(Kwong et al, , 2020Rice et al, 2019). Notably, the depression PRS accounted for between 1.5%-2.5% of the variance in past year MDD and MDE, paralleling the amount of variance explained in European samples (1.5%-3.2%) (Howard et al, 2019).…”

“…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).…”

Accelerated neurodevelopment of reward anticipation processing in adolescent girls with depression

“…At ages 9 to 12 girls and caregivers were asked about depression symptoms in the past month, and at ages 13 and older were asked about symptoms in the past month and past year. Participants were classified as having had MDD if they met DSM-IV criteria at any study visit by combined parent and child report (n=58; n=31 met criteria at ages 9-14; n=27 met criteria at ages [16][17][18][19][20]. Participants with MDD did not differ from those without MDD on sociodemographic variables (race, pubertal timing or tempo, and financial strain), age, or the number of fMRI scans (Table 1).…”

“…The peak incidence for MDD occurs during adolescence [16][17][18] , especially for girls 19 . Adolescence is also a developmental period in which reward-related activation, particularly of the VS, changes and peaks [20][21][22] .…”