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Background: Mood disorders and problematic substance use co-occur and confer reciprocal risk for each other. Few studies use analytic approaches appropriate for testing whether specific features of one disorder confer risk for the other. Methods: 445 participants (59.8% female, Mean age = 20.3 years) completed measures of depression and hypo/mania symptoms and substance use-related impairment; 330 had complete data at follow-up. Of these, 28% reported a history of depression, 4% of bipolar spectrum disorder, 11% of substance use disorder, and 55% reported substance-related impairment. Symptoms and domains of substance-related impairment were modeled in cross-sectional and cross-lagged panel network models. Results: Impulsive and interpersonal impairment were most highly comorbid with mood symptoms. Suicidal ideation, sadness, decreased need for sleep, and guilt were the symptoms …