Despite the well-established pervasive comorbidity of BD with other mental disorders (anxiety disorders, substance use disorders, behavior disorders), few of the studies of course build pre-existing comorbidity into study design. Nevertheless, the majority of studies of course and outcome showed that both anxiety and substance use disorders were associated with greater relapse rates and functional impairment. It is also important to distinguish the nature of the associations between comorbid disorders with mania and depression in order to develop meaningful approaches to the integration of comorbid conditions in the evaluation of course. For example, there is substantial evidence from prospective research that substance abuse may represent a complication of BD,58 whereas anxiety may comprise an early manifestation of BD.44,45,59 This suggests that substance use disorders may be considered an important outcome variable, whereas anxiety would be considered as a factor in the initial characterization of the index episode of BD that would predict differential course and outcome. Indeed, Sala and colleagues60 demonstrated differential outcome of youth with BD with and without comorbid anxiety disorders.

Clinical studies of people with BD have also noted the importance of evaluation of physical disorders.61 Recent community studies demonstrate that medical comorbidity is not an artifact of clinical sampling; evaluation of physical-mental comorbidity in World Mental Health countries showed that BD was associated with heart disease, hypertension, and back/neck pain.62 Although there is scant information on medical comorbidity in children with BD, some studies of children have reported links between BD and diabetes and cardiovascular diseases.63 The finding that physical symptoms may persist despite remission of psychiatric symptoms highlights the importance of comprehensive characterization of health in predicting course.19 Systematic incorporation of comorbidity into the designs of future studies is necessary to determine its influence on course as well as differential treatment response.

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