Familial risk for bipolar disorder, childhood trauma and anxiety in youth: Behavioral approach and inhibition systems as mediators of risk.

Background: Although the occurrence of mania defines the onset of bipolar I disorder, affected individuals often report years of prodromal psychiatric symptoms, often including anxiety and anxiety-related disorders. Moreover, rates of childhood trauma are elevated and may contribute to these conditions as well as mood symptoms. This study aimed to better understand risk factors of prodromal anxiety among youth at familial risk for bipolar disorder. In addition to the impact of trauma, we examined potential mediating roles of two motivational systems - the Behavioral Approach System (BAS) associated with reward motivation and Behavioral Inhibition Systems (BIS) associated with threat avoidance. Methods: Participants were 181 youth, 14-21 years old, with and without familial risk for bipolar I disorder followed prospectively. Using linear mixed-effects models, we examined associations of childhood trauma and familial risk with BIS and BAS subscale scores (Reward Responsiveness, Drive, Fun Seeking), and anxiety measures. We examined BIS and BAS as potential mediators in the relationship between familial risk and trauma, and anxiety, followed over a one-year period. Results: Results showed a positive association of familial risk with BIS (b=0.3, p = 0.02) and a negative association of familial risk with BAS Drive (b=-0.3, p = 0.03). Familial risk (b=0.5, p < 0.01) and trauma (b=0.2, p < 0.01) were associated with higher anxiety measures. BIS scores mediated the effect of familial risk (indirect effect: b=0.1, p = 0.03, proportion mediated=20 %), but not trauma, on anxiety ratings. Conclusion: Threat avoidance may be an important mechanism through which familial risk for bipolar I disorder predisposes individuals for anxiety.