BackgroundPrevious studies of bipolar disorders indicate that childhood abuse and substance abuse are associated with the disorder. Whether both influence the clinical picture, or if one is mediating the association of the other, has not previously been investigated.MethodA total of 587 patients with bipolar disorders were recruited from Norway and France. A history of childhood abuse was obtained using the Childhood Trauma Questionnaire. Diagnosis and clinical variables, including substance abuse, were based on structured clinical interviews (Structured Clinical Interview for DSM-IV Axis I disorders or French version of the Diagnostic Interview for Genetic Studies).ResultsCannabis abuse was significantly associated with childhood abuse, specifically emotional and sexual abuse (χ² = 8.63,p = 0.003 andχ² = 7.55,p = 0.006, respectively). Cannabis abuse was significantly associated with earlier onset of the illness (z = −4.17,p < 0.001), lifetime history of at least one suicide attempt (χ² = 11.16,p = 0.001) and a trend for rapid cycling (χ² = 3.45,p = 0.06). Alcohol dependence was associated with suicide attempt (χ² = 10.28,p = 0.001), but not with age at onset or rapid cycling. After correcting for possible confounders and multiple testing, a trend was observed for an interaction between cannabis abuse and childhood abuse and suicide attempt (logistic regression:r² = 0.06,p = 0.039). Significant additive effects were also observed between cannabis abuse and childhood abuse on earlier age at onset (p < 0.001), increased rapid cycling and suicide attempt (logistic regression:r² = 0.03–0.04,p < 0.001). No mediation effects were observed; childhood abuse and cannabis abuse were independently associated with the disorder.ConclusionsOur study is the first to demonstrate significant additive effects, but no mediation effects, between childhood abuse and cannabis abuse on increased clinical expressions of bipolar disorders.