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Increasing risk of depression through three generations
Numerous family studies of adults have shown the familial character of major depression and studies of offspring of parents with major depression show a 3-fold higher risk of developing depression among children. None of the published studies have gone beyond 2 generations. A recent study investigated the familial aggregation of psychiatric disorders by following-up grandparents (generation 1) with and without depression, their children (generation 2) up to the age adult and had their own children (generation 3) who were aged an average of 12 years.
A longitudinal, retrospective cohort, family study examined the effect of the parents' and grandparents' depression status on the prevalence of psychiatric disorders and the functioning of 161 participant grandchildren. Diagnostic interviews were conducted and diagnostic assessments were administered by clinicians blind to diagnoses of previous generations and to previous history information.
A proportion (59.2%) of grandchildren who had both parents and grandparents with depression already had a psychiatric disorder (at the age of 12 years). The risk of anxiety disorders in these grandchildren was increased five fold in comparison with those whose grandparents were depressed but parents were not. Moreover, if impairment criteria are added to the depression diagnosis, 67.6% of the grandchildren with two generations with depression had a psychiatric disorder. The risk of developing a psychiatric disorder was not higher in children whose parents were depressed but whose grandparents were not. However, grandchildren with a depressed parent had poor overall mental functioning, regardless of their grandparents' depression.
Thus, information on family history of depression, on its severity and impairment, is important for identifying subjects at high risk of developing psychiatric disorders at an early age. Young children with depressed parents and grandparents, who present anxiety disorders, should be treated for depression without waiting.
Weissman MM, Wickramaratne P, Nomura Y, Warner V, Verdeli H, Pilowsky DJ, Grillon C, Bruder G. Families at high and low risk for depression: a 3-generation study. Arch Gen Psychiatry 2005, 62: 29-36.

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