Characterizing Developmental Trajectories and the Role of Neuropsychiatric Genetic Risk Variants in Early-Onset Depression

Abstract

Importance: Depression often first manifests in adolescence. Thereafter, individual trajectories vary substantially, but it is not known what shapes depression trajectories in youth. Adult studies suggest that genetic risk for schizophrenia, a psychiatric disorder with a neurodevelopmental component, may contribute to an earlier onset of depression. Objective: To test the hypothesis that there are distinct trajectories of depressive symptoms and that genetic liability for neurodevelopmental psychiatric disorders (eg, schizophrenia, attention deficit/hyperactivity disorder [ADHD]), as well as for major depressive disorder (MDD), contribute to early-onset depression. Design, Setting, and Participants: The Avon Longitudinal Study of Parents and Children is an ongoing, prospective, longitudinal, population-based cohort that has been collecting data since September 6, 1990, including data on 7543 adolescents with depressive symptoms at multiple time points. The present study was conducted between November 10, 2017, and August 14, 2018. Main Outcomes and Measures: Trajectories based on self-reported depressive symptoms dichotomized by the clinical cutpoint; MDD, schizophrenia, and ADHD polygenic risk score (PRS) were predictors. Results: In 7543 adolescents with depression data on more than 1 assessment point between a mean (SD) age of 10.64 (0.25) years and 18.65 (0.49) years (3568 [47.3%] male; 3975 [52.7%] female), 3 trajectory classes were identified: persistently low (73.7%), later-adolescence onset (17.3%), and early-adolescence onset (9.0%). The later-adolescence-onset class was associated with MDD genetic risk only (MDD PRS: odds ratio [OR], 1.27; 95% CI, 1.09-1.48; P =.003). The early-adolescence-onset class was also associated with MDD genetic risk (MDD PRS: OR, 1.24; 95% CI, 1.06-1.46; P =.007) but additionally with genetic risk for neurodevelopmental disorders (schizophrenia PRS: OR, 1.22; 95% CI, 1.04-1.43; P =.01; ADHD PRS: OR, 1.32; 95% CI, 1.13-1.54; P