Elevated Galvanic Skin Response and Associated Brain Network Patterns in Youth at High Familial Risk for Bipolar Disorder.

Objective: Autonomic nervous system (ANS) dysfunction may be a key neuropathological feature of bipolar disorder. There is limited understanding of how perturbations in the ANS manifest and their relation to brain function in youth with a familial risk for bipolar disorder. Method: Galvanic skin response and functional magnetic resonance imaging data during a continuous performance task with emotional and neutral distractors were collected from high-risk youth with depressive and/or anxiety symptoms and healthy controls (HCs). We compared skin conductance response (SCR) values from galvanic skin response data collected during imaging as an index of ANS arousal between groups. Then, we computed seed-based functional connectivity maps using generalized psychophysiological interaction analysis and applied a general linear model to examine associations between SCR values and functional connectivity patterns within the high-risk group. Results: We included 31 high-risk youth and 15 HCs in our analysis. The high-risk group showed significantly higher maximum (1.29 ± 1.32 μS vs 0.65 ± 0.62 μS, Conclusion: Our findings provided preliminary evidence of ANS dysfunction in high-risk youth compared with HCs. Furthermore, functional connectivity patterns in prefrontal-limbic regions may be associated with ANS arousal, offering novel insights into ANS-related neural mechanisms and deepening our understanding of emotional dysregulation from peripheral and central perspectives in these youth. Clinical trial registration information: Mechanism of Antidepressant-Related Dysfunctional Arousal in High-Risk Youth; https://clinicaltrials.gov/ct2/show; NCT02553161. Diversity & Inclusion Statement: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants.