IN CONTRAST to the debates of the late 1970s, when large-scale epidemiologic studies, family genetic studies, and the Dunedin Multidisciplinary Health and Development Study1 were initiated, it is now well established that major depressive disorder (MDD) is a disorder that usually begins in adolescence or early adulthood. It is also clear that prepubertal-onset MDD is uncommon and that girls are at a higher risk than boys after puberty, but not before.2- 4 Family genetic studies have explored the relationship between age at onset of MDD and familial loading. The hypothesis was that patients with MDD that began early (at that time, it was uncertain what was considered early) would have the highest number of biological relatives affected. The family studies confirmed the hypothesis that the earlier the age at onset (especially an onset before age 20 years), the higher the familial loading and specificity of familial transmission.5 In the late 1980s, a series of studies was conducted on high-risk children (the offspring of depressed parents).6,7 These studies showed that when compared with controls, the children of depressed parents were at a 2- to 3-fold increased risk of MDD and that prepubertal-onset MDD occurred more frequently in the offspring of affected parents.6 The epidemiologic and family study findings accelerated interest in understanding the clinical course and later the treatment of juvenile-onset depression. They also suggested that juvenile-onset depression may be heterogeneous.
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