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Background: This article examines associations between DSM-IV depressive disorders, their natural course, other psychopathology, and parental major depression in a community sample of adolescents and young adults. Methods: Baseline and 4-year follow-up data were used from the Early Developmental Stages of Psychopathology Study, a prospective-longitudinal community study of adolescents and young adults. Results are based on 2427 subjects who completed the follow-up and for whom diagnostic information for both parents was available. DSM-IV mental disorders in respondents were assessed using the Munich- Composite International Diagnostic Interview. Information on depression in parents was collected as family history information from the respondents and from diagnostic interviews with parents of the younger cohort. Results: Offspring with I (odds ratio [OR], 2.7; 95% confidence interval [ C1], 2.1-3.5) or 2 affected parents (OR, 3.0; 95% Cl, 2.2-4.1) had an increased risk for depression. They also had a higher risk for substance use (I parent affected: OR, 1.4; 95% Cl, 1.1-1.7; both parents affected: OR, 1.4; 95% Cl, 1.0-1.8) and anxiety disorders (I parent affected: OR, 1.6; 95% CI, 1.3-1.9; both parents affected: OR, 2.1; 95% Cl, 1.6-2.8). There were no differences whether mother or father was affected. Parental depression was associated with an earlier onset and a more malignant course (severity, impairment, recurrence) of depressive disorders in offspring. Conclusions: Major depression in parents increases the overall risk in offspring for onset of depressive and other mental disorders and influences patterns of the natural course of depression in the early stages of manifestatio