Bipolar disorder and substance misuse: pathological and therapeutic implications of their comorbidity and cross-sensitisation

Background Bipolar disorder has a high co-occurrence with substance use disorders, but the pathophysiological mechanisms have not been adequately explored. Aims To review the role of stress in the onset and recurrence of affective episodes and substance misuse. Method We review the mechanisms involved in sensitisation (increased responsivity) to recurrence of stressors, mood episodes and cocaine use. Results Evidence suggests that intermittent stressors, mood episodes and bouts of cocaine use not only show sensitisation to themselves, but cross-sensitisation to the others contributing to illness progression. Converseley, an understanding of the common mechanisms of sensitisation (such as regionally selective alterations in brain derived neurotrophic factor (BDNF) and hyperactivity of striatally based habit memories), could also result in single therapies (such as N-acetylcysteine) having positive effects in all three domains. Conclusions These interacting sensitisation processes suggest the importance of early intervention in attempting to prevent increasingly severe manifestations of bipolar illness and substance misuse progression.