Selecting early onset MDD probands for genetic studies: results from a longitudinal high-risk study

Recent studies have found high rates of familial aggregation of major depression (MDD) in relatives of depressed children coming for treatment, leading investigators to suggest that probands for genetic studies of MDD should be selected from samples of depressed children being brought for treatment. Implicit in this recommendation is the assumption that childhood and adult depression are similar disorders. This assumption in turn implies that children with prepubertal or adolescent onset depression are at high risk for having recurrent episodes of MDD that continue into adulthood. The data supporting this latter hypothesis, however, is limited and contradictory. In this article we report results from a high-risk longitudinal family study in which we explored the recurrence and continuity into adulthood of prepubertal or adolescent onset MDD in offspring who were at high or low risk for MDD, by virtue of their parental depression status. One hundred eighteen offspring from 55 families in which one or more parents had MDD and 50 offspring from 21 families in which neither parent had MDD were followed for more than 10 years (all offspring were 20 years or older at the end of follow-up time) and blindly reassessed using a semistructured diagnostic instrument. Offspring with childhood/adolescent onset MDD were at significantly greater risk for recurrence in adulthood (after age 25) as compared with offspring without an onset of childhood/adolescent MDD, if they had a history of parental MDD. In contrast, among offspring without a history of parental MDD, those with childhood/adolescent onset MDD were at no greater risk for continuing to have MDD in adulthood (after age 25) than those without childhood/adolescent onset MDD. Moreover, there was a trend for offspring with childhood/adolescent onset MDD to be at greater risk for recurrence after age 25 if they had a history of parental MDD, as compared with offspring without a history of parental MDD (60 vs. 18%). We conclude that childhood/adolescent onset MDD is a heterogeneous disorder, with family history of MDD appearing to define a subtype of childhood/adolescent onset MDD that is recurrent and continues into adulthood. Our findings suggest that caution should be exercised in selecting depressed children and adolescents brought for treatment as probands in genetic studies of early onset MDD. A conservative strategy would be to select only those depressed children and adolescents with a family history of MDD and reassess the treated sample as they mature, ensuring that they go on to have MDD in adulthood. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:93-101, 2000