Neural functional connectivity changes to psychosocial stress in young adults with bipolar disorder and preliminary associations with clinical trajectories

Background Stress-related mechanisms are implicated in the pathophysiology of bipolar disorder and may contribute to heterogeneity in illness course. Yet, there is a lack of study investigating the neural mechanisms underlying the stress response in this condition. This study investigated changes in amygdala activation and functional connectivity in response to acute psychosocial stress in young adults with bipolar disorder and explored relations with clinical phenotype and prospective mood symptoms. Methods 42 young adults [19 with bipolar disorder, age(mean) +/- SD =21.4 +/- 2.2 years] completed a modified version of the Montreal Imaging Stress Task. Amygdala activation and functional connectivity with prefrontal cortex (PFC) regions of interest was calculated for control and stress conditions. Main effects of group, condition, and group by condition interaction on amygdala activation and connectivity were modeled. A subset of bipolar participants completed 1-year follow-up assessments. Relations between neural responses to stress with concurrent substance use and prospective mood symptoms were explored. Results There were no between-group differences in amygdala activation or functional connectivity during the control condition. Increased right amygdala-right rostral PFC (rPFC) functional connectivity to stress was observed in bipolar disorder, compared to typically developing controls. In bipolar disorder, greater increase in right amygdala-right rPFC functional connectivity to stress was associated with less frequent cannabis use, and prospectively with shorter duration and lower severity of depression symptoms over follow-up. Conclusion Results from this preliminary study suggest differences in frontolimbic functional connectivity responses to stress in young adults with bipolar disorder and associations with cannabis use and prospective mood symptoms.