Polygenic risk for depression, anxiety and neuroticism are associated with the severity and rate of change in depressive symptoms across adolescence

• Published in: Journal of child psychology and psychiatry 2021-12, Vol.62 (12), p.1462-1474
• Main Authors: Kwong, Alex S. F., Morris, Tim T., Pearson, Rebecca M., Timpson, Nicholas J., Rice, Frances, Stergiakouli, Evie, Tilling, Kate
• Format: Article
• Language: English
• Subjects: adolescence; Adolescent; Adolescents; Adult; Adults; ALSPAC; Analysis; Anxiety; Change agents; Child; Child & adolescent psychiatry; Child development; Cross-Sectional Studies; Depression (Psychology); Depression - genetics; Depressive Disorder, Major - epidemiology; Depressive Disorder, Major - genetics; Depressive personality disorders; depressive symptoms; development; Effect Size; Evidence; Genetic Predisposition to Disease - genetics; Genome-Wide Association Study; Genomes; Genomics; Humans; longitudinal; Longitudinal Studies; Mental depression; Multifactorial Inheritance - genetics; Neuroticism; Polygenic risk scores; Psychiatric symptoms; Psychiatry; Schizophrenia; Severity; trajectories; Twin studies; Variants; Young Adult; Young adults
• ISSN: 0021-9630; 1469-7610
• DOI: 10.1111/jcpp.13422

Background Adolescence marks a period where depression will commonly onset. Twin studies show that genetic influences play a role in how depression develops and changes across adolescence. Recent genome‐wide association studies highlight that common genetic variants – which can be combined into polygenic risk scores (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 associations between PRS for five psychiatric traits and depressive symptoms measured across adolescence using cross‐sectional and growth‐curve models. The five PRS were as follows: depression (DEP), major depressive disorder (MDD), anxiety (ANX), neuroticism (NEU) and schizophrenia (SCZ). Methods We used data from over 6,000 participants of the Avon Longitudinal Study of Parents and Children (ALSPAC) to examine associations between the five PRS and self‐reported depressive symptoms (Short Mood and Feelings Questionnaire) over 9 occasions from 10 to 24 years. The PRS were created from well‐powered genome‐wide association studies conducted in adult populations. We examined cross‐sectional associations between the PRS at each age and then again with longitudinal trajectories of depressive symptoms in a repeated measures framework using multilevel growth‐curve analysis to examine the severity and the rate of change. Results There was strong evidence that higher PRS for DEP, MDD and NEU were associated with worse depressive symptoms throughout adolescence and into young adulthood in our cross‐sectional analysis, with consistent associations observed across all nine occasions. Growth‐curve analyses provided stronger associations (as measured by effect sizes) and additional insights, demonstrating that individuals with higher PRS for DEP, MDD and NEU had steeper trajectories of depressive symptoms across development, all with a greater increasing rate of change during adolescence. Evidence was less consistent for the ANX and SCZ PRS in the cross‐sectional analysis, yet there was some evidence for an increasing rate of change in adolescence in the growth‐curve analyses with the ANX PRS. Conclusions These results show that common genetic variants as indexed by varying psychiatric PRS show patterns of specificity that influence both the severity and rate of change in depressive symptoms throughout adolescence and then into young adulthood. Longitudinal data that make use of repeated