Genetic factors predicting risk of mood disorders in adolescents

Adolescence is a sensitive period for the onset of mood disorders. Many adolescents experience mood symptoms, which for some are transient and pass over time and for others lead to a mood disorder diagnosis. Mood disorders are substantially heritable and those at highest genetic risk tend to have an earlier onset. The present review summarizes recent advances in our understanding of genetic factors contributing to mood disorders in adolescents.

Genetic predispositions play a critical part in the development of mood disorders, including major depression and bipolar disorder. Both cross-sectional and longitudinal studies have consistently found that individuals reporting mood symptoms during adolescence have higher polygenic risk for both mood disorders and other psychiatric disorders than those without symptoms. Polygenic Risk Scores (PRS) that aggregate the effects of thousands of genetic variants can improve individual risk prediction for bipolar disorder when combined with clinical and environmental factors. Genetically informative designs, either using observed genotypes summarized in PRS or the occurrence of the disorder in family members summarized in Family Genetic Risk Scores (FGRS) are also used to investigate mechanisms underlying associations with risk factors. Recent studies suggest that teens whose peers are genetically vulnerable to depression have an increased risk for depression compared to teens with the same genetic risk but whose peers are not genetically vulnerable. This indicates a direct environmental effect. These studies illustrate that both family-based and molecular-based genetic approaches can help in diagnosing and understanding the origins of mood disorders in adolescents.

Adolescent-onset mood disorders are associated with increased genetic risk relative to later-onset. Although not currently clinically applicable, genetic factors, with a focus on PRS and FGRS, can help to predict onset and course of mood disorders in adolescents. The use of PRS and FGRS, combined with environmental factors, improves prediction models for mood disorders in adolescents. Additionally, it also provides information on the etiology of these disorders, for example by examining parent-offspring and peer group associations in genetically informative study designs.