Increased functional connectivity of amygdalar-frontal pathways in patients with alcohol use disorder and childhood trauma.

Childhood trauma (CT) often co-occurs with alcohol use disorder (AUD) and is associated with poor treatment outcome. We could demonstrated that patients with AUD and a history of childhood trauma showed reduced structural connectivity of the amygdala. Here, we additionally aimed to investigate fronto-limbic functional connectivity (FC) in patients with AUD with (AUD-CT) and without (AUD-noCT) CT. Based on findings in CT, we hypothesized reduced FC of the amygdala with the prefrontal cortex in AUD-CT and worse treatment outcome compared to AUD-noCT. Resting state fMRI scans were acquired in abstinent inpatients with AUD and healthy controls (HCs). We compared bilateral amygdala FC between AUD-CT (n = 21), AUD-noCT (n = 22), and HC (n = 27) using seed-based connectivity (SBC) and region-of-interest to region-of-interest (ROI-ROI) analysis. Sociodemographic and alcohol-specific variables (percent days abstinent, PDA) were assessed at treatment admission and three-month follow-up. The Childhood Trauma Questionnaire (CTQ) assessed trauma severity. SBC analysis revealed that AUD-CT showed increased FC of the left and right amygdala with the medial prefrontal cortex and left paracingulate gyrus compared to HC. AUD-CT showed increased ROI-ROI FC of the left with the right amygdala and the right amygdala with the medial prefrontal cortex. Moreover, AUD-CT exhibited a greater reduction of PDA at three-month follow-up compared to AUD-noCT. Increased FC of the amygdala, the medial prefrontal cortex, and paracingulate gyrus in AUD-CT might be a compensatory adaption to the reduced structural connectivity of the amygdala. Those specific alterations of FC in AUD-CT may represent a distinguishable neurobiological subtype of AUD, possibly underlying the complex clinical picture and worse treatment outcome.