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Substance use disorders (SUDs) have been estimated to occur in 40% to 60% of patients with bipolar disorders. Most reports suggest that these patients have more-severe courses and worse outcomes, including a greater risk for depression. However, the precise nature of these associations and their underlying mechanisms have not been well clarified. Several hypotheses have been proposed; e.g., an underlying biological vulnerability to SUDs might pose an additional risk for mood instability, substances of abuse might directly affect mood stability, or the SUD might impair mood-stabilizer medication adherence. These researchers analyzed 2 years of follow-up data on 3750 patients with bipolar I or II disorder enrolled in the prospective Systemati…