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

Abstract

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.

Recent Perceived Stress, Amygdala Reactivity to Acute Psychosocial Stress, and Alcohol and Cannabis Use in Adolescents and Young Adults With Bipolar Disorder

“…As previously published (27), the bipolar disorder group showed greater HDRS scores and had more individuals who used tobacco over the past month compared to the typically developing group. No other between group differences in demographic or clinical characteristics were observed.…”

“…Bipolar disorder is progressive and stress response is thought to sensitize with age in bipolar disorder ( 21 ). While there were no between-group differences in amygdala reactivity ( 27 ), it is possible greater between-group differences in amygdala response to stress will emerge over time, although we did not observe main effects of age or group by age interactions on amygdala reactivity to the stress condition. While we can only speculate, stress may potentiate amygdala reactivity in adolescents/young adults and over time group differences in stress-induced amygdala reactivity may become more robust.…”

“…Several limitations should be noted. As previously discussed (27), findings should be considered preliminary. We employed a ROI approach to test our a priori clinical hypothesis and balance study sensitivity while also reducing the number of comparisons performed (50).…”

“…All participants were asked to not consume alcohol or drugs for the day preceding the MRI scan. A full description of this dataset has been published in a prior manuscript ( 27 ). The University of Texas at Austin Institutional Review Board approved all study procedures and all participants provided written consent prior to study participation.…”

“…This report is a secondary analysis of a previously published dataset (27) in which results suggested differences in stress response early in illness course in bipolar disorder, compared to typically developing adolescents/young adults, and suggested variation in neural response to stress relates to substance use and mood symptom recurrence. While the primary analysis did not observe between-group differences in amygdala activation, this secondary analysis sought to investigate if recent perceived stress relates to variation in amygdala response to acute stress.…”