Sex Differences in the Associations Between Transdiagnostic Trauma Distress and Alcohol Cue-Reactivity in AUD: Implications for TMS Target Selection

Abstract

Abstract Introduction: TMS has shown great promise for the treatment of depression, OCD, and other psychiatric conditions, with some evidence for sex differences in efficacy. However, the precise targeting of TMS for alcohol use disorder (AUD) and associated traumatic experiences remains unclear. According to neurobiological literature, brain function during alcohol cue-reactivity may play a key role in TMS target selection, however activation patterns can also vary by sex. Objective: Taken together, we aimed to 1) examine the relationship between a transdiagnostic trauma metric and alcohol cue-reactivity in males and females separately, and 2) compare the transdiagnostic trauma approach to traditional PTSD diagnosis. Methods: In 72 Veterans (16F) with AUD, trauma distress transdiagnostic factor was previously identified through principal components analysis of self-reported symptoms. Bivariate correlations assessed how trauma distress relates to activation and functional connectivity in a-priori defined, core incentive salience nodes during an fMRI cue-reactivity task (CUE) in females and males separately. Independent samples t-tests compared the same metrics by PTSD diagnosis. Results: In females, transdiagnostic trauma distress was significantly associated with hypoactivation in the left lateral PFC and decreased connectivity in incentive salience regions (L.NAcc to L.Amygdala and R.NAc to L.Amygdala, L.AntInsula, L.NAcc, L.posInsula, R.Putamen; -0.6<r<-0.5, p<0.05). By contrast, in males, trauma distress was not associated with CUE activation, nor functional connectivity. Further, neither females nor males showed differences in CUE activation or connectivity based on PTSD diagnosis Conclusions: Females with higher trauma distress showed decreased activation and connectivity in core nodes of the incentive salience network during an alcohol cue-reactivity task, while males did not. Therefore, separate analyses by sex may be beneficial to define neuromodulation targets for those with AUD and traumatic experiences. Further, examining trauma symptoms continuously and transdiagnostically may better explain brain function in AUD than binary PTSD diagnosis. Research Category and Technology and Methods Clinical Research: 18. Functional Brain Imaging Keywords: Alcohol Use Disorder, Trauma, Cue-Reactivity, Sex Differences