The Mood Disorder Questionnaire is a screening measure for bipolar disorder, previously found to comprise separate Positive and Negative Activation subscales. We sought to replicate these factors and examine their associations with a range of psychopathology. To further explicate the nature of Negative Activation, we examined associations with the Difficulties in Emotion Regulation Scale, a measure of emotion dysregulation. The sample consisted of 1,787 participants from an outpatient treatment facility. Confirmatory factor analysis replicated the existence of Positive and Negative Activation subscales. Logistic regressions, as hypothesized, found that Positive Activation was positively associated only with bipolar disorder, while Negative Activation was associated with almost all disorders. The Impulse and Goals subscales of the Difficulties in Emotion Regulation Scale were uniquely associated with Negative Activation, suggesting it may specifically assess impulsive behavior in emotional situations. The findings suggest that it may be important to attend to both Mood Disorder Questionnaire subscales.