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

Frances Rice

doi:10.1186/gm189

Abstract

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.

Highlights

There is heterogeneity between depression in childhood, adolescence and adulthood in terms of the gender composition of a ected cases, prevalence, rates of recurrence and risk factors
Features of childhood/adolescent depression compared with adult depression e criteria used to diagnose depression in children and adolescents are the same as those used in adults, with the only exception being that the Diagnostic and Statistical Manual of Mental Disorders criteria allow irritable mood instead of depressed mood as a core symptom for children and adolescents [9]
That study found that childhood/adolescent Major depressive disorder (MDD) that did not recur in early adult life was characterized by a male prepon derance and comorbidity with externalizing disorders, whereas childhood/adolescent MDD with recurrence in early adult life was characterized by a female prepon derance and comorbidity with anxiety disorders [10]

Summary

Introduction

There is heterogeneity between depression in childhood, adolescence and adulthood in terms of the gender composition of a ected cases, prevalence, rates of recurrence and risk factors. Individuals with depressive episodes in childhood/adolescence showed elevated rates of a range of childhood risk factors, including perinatal insults, parental psychopathology, motor skill deficits and care taker instability This finding points to the likelihood of etiological heterogeneity between childhood/ adolescent and adult depression. That study found that childhood/adolescent MDD that did not recur in early adult life was characterized by a male prepon derance and comorbidity with externalizing disorders, whereas childhood/adolescent MDD with recurrence in early adult life was characterized by a female prepon derance and comorbidity with anxiety disorders [10] This issue of etiological heterogeneity between childhood and adolescent depression has been examined by family studies, as reviewed below

Objectives

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Conclusion