Of course, there are several limitations to this analysis. First, primarily alcohol-dependent subjects in treatment, their relatives and control families were enrolled into this study. This might explain the rather high rate of alcohol dependence diagnosis of more than three quarters in this bipolar sample compared to previous studies. Second, several previous investigations included first-episode manic patients to overcome potential bias caused by the number of affective episodes and chronic course of bipolar disorders. The COGA sample enrolled subjects with and without alcohol dependence; its target group was not first-episode bipolar subjects. Thus, more chronic bipolar disorder individuals who were currently not in treatment were recruited. Chronic patients have a higher rate of previous affective episodes which in turn increase the likelihood of future affective episodes. When subjects at different stages of their disease are investigated, it is more difficult to identify other course predictors (33) and to evaluate the influence of a comorbid disorder on prognosis of bipolar disorder.
