Genetics of childhood and adolescent depression: insights into etiological heterogeneity and challenges for future genomic research

There is heterogeneity between depression in childhood, adolescence and adulthood in terms of the gender composition of affected cases, prevalence, rates of recurrence and risk factors. This raises complex questions for refining the phenotype for molecular genetic studies of depression and the selection of appropriate proband groups. This article aims to provide a review of issues arising from family, twin and adoption studies of relevance to molecular genetic studies, and to summarize molecular genetic findings on childhood/adolescent depression. While retrospective studies of adults suggest greater familial aggregation among those with an earlier age of onset, prospective studies do not confirm this association. In fact, taken together, evidence from family and twin studies suggests that prepubertal depression is more strongly associated with psychosocial adversity, is less heritable and shows lower levels of continuity with adult depression than either adolescent or adult depression. Adolescent depressive symptoms and disorder show similar levels of heritability to depression in adult life, although there is only one twin study of adolescent depressive disorder, and heritability estimates of depressive symptoms vary widely between studies. This variability in heritability estimates is partly attributable to age and informant effects. Adoption studies and other intergenerational transmission designs show that the transmission of depression between parents and children involves genetic and environmental processes, with converging evidence that environmental processes are most important. Molecular genetic studies of childhood/adolescent depression have to date used a candidate gene approach and focused on genes already examined in adult studies. Prospective longitudinal studies of community and high-risk samples are needed to clarify issues of etiological heterogeneity in depression, and these should in turn inform the planning of molecular genetic studies.