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 (BD). There is limited understanding of how perturbations in the ANS manifest and their relation to brain function in youth with a familial risk for BD. Method Galvanic skin response (GSR) and functional magnetic resonance imaging (fMRI) data during a continuous performance task with emotional and neutral distractors (CPT-END) were collected from high-risk youth with depressive and/or anxiety symptoms and healthy controls (HCs). We compared skin conductance response (SCR) values from GSR data collected during imaging as an index of ANS arousal between groups. Then, we computed seed-based functional connectivity maps using generalized psychophysiological interaction (gPPI) analysis, and applied a general linear model (GLM) 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, p=0.048) and mean (0.26 ± 0.26 μS vs. 0.14 ± 0.11 μS, p=0.028) SCR values compared to HCs. Within high-risk group, SCR values were not significantly correlated with emotional scores. Mean SCR values in high-risk youth were positively correlated with the functional connectivity between the right ventrolateral prefrontal cortex and both the left amygdala and right thalamus, and these associations were not observed in the HC group. Conclusion Our findings provided preliminary evidence of ANS dysfunction in high-risk youth compared to 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.