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The role of fear and anxiety in the familial risk for major depression: a three-generation study

  • V. Warner (a1) (a2), P. Wickramaratne (a1) (a2) and M. M. Weissman (a1) (a2)

The overlap between anxiety and major depressive disorder (MDD), the increased risk for depression and anxiety in offspring of depressed parents, the sequence of onset with anxiety preceding MDD, and anxiety as a predictor of depression are well established. The specificity of anxiety disorders in these relationships is unclear. This study, using a longitudinal high-risk design, examined whether anxiety disorders associated with the emotions fear and anxiety mediate the association between parental and offspring depression.


Two hundred and twenty-four second-generation and 155 third-generation descendants at high and low risk for depression because of MDD in the first generation were interviewed over 20 years. Probit and Cox proportional hazard models were fitted with generation 2 (G2) or G3 depression as the outcome and parental MDD as the predictor. In G2 and G3, fear- (phobia or panic) and anxiety-related [overanxious or generalized anxiety disorder (GAD)] disorders were examined as potential mediators of increased risk for offspring depression, due to parental MDD.


In G2, fear-related disorders met criteria for mediating the association between parental MDD and offspring MDD whereas anxiety-related disorders did not. These results were consistent, regardless of the analytic methods used. Further investigation of the mediating effect of fear-related disorders by age of onset of offspring MDD suggests that the mediating effect occurs primarily in adolescent onset MDD. The results for G3 appear to follow similar patterns.


These findings support the separation of anxiety disorders into at least two distinct forms, particularly when examining their role in the etiology of depression.

Corresponding author
*Address for correspondence: V. Warner, M.P.H., New York State Psychiatric Institute, 1051 Riverside Drive, Unit 24, New York, NY 10032, USA.(Email:
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