Amygdala-hippocampal connectivity changes during adute psychosocial stress: Joint effect of early life stress and oxytocin

Previous evidence shows that acute stress changes both amygdala activity and its connectivity with a distributed brain network. Early life stress (ELS), especially emotional abuse (EA), is associated with altered reactivity to psychosocial stress in adulthood and moderates or even reverses the stress-attenuating effect of oxytocin (OXT). The neural underpinnings of the interaction between ELS and OXT remain unclear, though. Therefore, we here investigate the joint effect of ELS and OXT on transient changes in amygdala-centered functional connectivity induced by acute psychosocial stress, using a double-blind, randomized, placebo-controlled, within-subject crossover design. Psychophysiological interaction analysis in the placebo session revealed stress-induced increases in functional connectivity between amygdala and medial prefrontal cortex, posterior cingulate cortex, putamen, caudate and thalamus. Regression analysis showed that EA was positively associated with stress-induced changes in connectivity between amygdala and hippocampus. Moreover, hierarchical linear regression showed that this positive association between EA and stress-induced amygdala-hippocampal connectivity was moderated after the administration of intranasal OXT. Amygdala-hippocampal connectivity in the OXT session correlated negatively with cortisol stress responses. Our findings suggest that altered amygdala-hippocampal functional connectivity during psychosocial stress may have a crucial role in the altered sensitivity to OXT effects in individuals who have experienced EA in their childhood