Females with ADHD (n=140) had a 2.5 times higher risk of MD in adolescence compared with control females without ADHD (n=122), adjusting for co-occurring psychiatric disorders. For females with ADHD, MD was associated with an earlier age at onset, greater than twice the duration, more severe depression-associated impairment, a higher rate of suicide ideation, and a greater likelihood of psychiatric hospitalization compared to control females. Parental MD and proband mania were significant predictors of MD among females with ADHD, independently of other predictors. The study concluded that MD that emerges in the context of ADHD in females is a severe co-occurring disorder with significant impairment that deserves further clinical and research attention. Females with and without ADHD were recruited from psychiatric and pediatric settings. All subjects were followed for 5 years into adolescence and young adulthood and reassessed in multiple nonoverlapping domains that pertained to psychiatric, cognitive, interpersonal, family, and educational functioning. Psychiatric assessments relied on the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiologic Version for subjects younger than 18 years old and the Structured Clinical Interview for DSM-IV. Cognitive and psychosocial functioning were measured with the DSM-IV Global Assessment of Functioning and the Social Adjustment Inventory for Children and Adolescents, which was completed by mothers and youth 12 years old or older. Socioeconomic status was measured with the Hollingshead scale, and family environment at baseline was assessed with the Moos Family Environment Scale. Parental psychiatric history was measured with the Structured Clinical Interview for DSM-III-R at the baseline assessment. 4 tables, 1 figure, and 44 references