Feelings of anger and irritability are prominent symptoms of bipolar disorder (BD) that may occur during hypomanic, depressive and, especially, during mixed mood states. We aimed to determine whether such constructs are associated with the conversion to BD in subjects with a history of unipolar depression. Data were derived from the depressed participants of Netherlands Study of Depression and Anxiety with 9 years of follow-up. Hypomania was ascertained using the Composite International

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... ic Interview at 2, 4, 6, and 9 years follow-up. Cross-sectionally, we studied the association between prevalent hypomania and anger related constructs with the "Spielberger Trait Anger subscale," the "Anger Attacks" questionnaire, the cluster B personality traits part of the "Personality Disorder Questionnaire," and "aggression reactivity." Prospectively, we studied whether aggression reactivity predicted incident hypomania using Cox regression analyses. Cross-sectionally, the bipolar conversion group (n = 77) had significantly higher scores of trait anger and aggression reactivity, as well as a higher prevalence on "anger attacks," "antisocial traits," and "borderline traits" compared to current (n = 349) as well as remitted (n = 1159) depressive patients. In prospective analyses in 1744 participants, aggression reactivity predicted incident hypomania (n = 28), with a multivariate-adjusted hazard ratio of 1.4 (95% confidence interval: 1.02-1.93; p = .037). Anger is a risk factor for conversion from unipolar depression to BD. In addition, patients who converted to BD showed on average anger, agitation and irritability than people with a history of unipolar depression who had not converted.