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Am J Prev Med. 2006 Dec;31(6 Suppl 1):S126-35.

Implications of high-risk family studies for prevention of depression.

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Division of Pediatric Translational Research and Treatment Development, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA.


The high-risk family study is a powerful design that facilitates identification of early forms of expression of depression and premorbid vulnerability, risk, and protective factors that are important for defining prevention targets and program foci. This paper (1) highlights the strengths of high-risk studies for informing early intervention efforts; (2) summarizes findings of familial aggregation from controlled high-risk studies of depression; and (3) briefly reviews evidence for potential mediators (i.e., early forms of expression, vulnerability factors) that explain familial risk and for moderators (i.e., interactive risk and protective factors) that enhance or minimize familial risk. New data from the Yale High-Risk Study of Comorbidity of Substance Use and Affective Disorders are presented to exemplify strategies for identifying specific familial pathways to depression among offspring of parents with substance and anxiety disorders. Likewise, parental depression is associated with a range of emotional and behavioral problems, including anxiety and conduct disorder, in their offspring. These nonspecific effects, together with emerging findings on mechanisms of risk, support early intervention efforts that target a range of youth at risk for depression through multipronged approaches that attend to the individual characteristics of the child and parent, clinical comorbidity, and the broader family and social context.

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