The interplay between alcohol use disorder (AUD) and anxiety disorders (ANX) is well-documented, yet the underlying neurobiological mechanisms remain elusive. This study aims to elucidate these mechanisms by examining the resting-state functional connectivity (RSFC) within the salience network and to the amygdala, both implicated in alcohol and anxiety disorders. We analyzed data from 264 inpatient participants culled from a wider group of 518 inpatients at The Menninger Clinic in Houston, TX, categorized into four groups (n = 66 each) based on DSM-IV diagnoses: AUD without ANX (AUD), ANX without AUD (ANX), concurrent AUD and ANX (BOTH), and neither (NEITHER). Our findings reveal significant RSFC differences, particularly between the right supramarginal gyrus (SMG) and 1) right rostral prefrontal cortex (RPFC) (corrected p = 0.029
RSFC significantly higher in NEITHER than in BOTH), and 2) left supramarginal gyrus (SMG) (corrected p = 0.016
RSFC significantly higher in AUD and NEITHER than in BOTH). Furthermore, correlations with a clinical measure for alcohol use (World Health Organization Alcohol, Smoking and Substance Involvement Screening Test
WHO ASSIST) indicated significant relationships: WHO ASSIST alcohol scores negatively correlated with right SMG to right RPFC RSFC (r = -0.14, p = 0.02) and positively correlated with the interhemispheric SMG RSFC (r = 0.17, p = 0.006). This research enhances our understanding of the complex neurobiological interconnections between alcohol use and anxiety disorders, suggesting a disrupted neural architecture that may underpin the behavioral manifestations observed in these highly comorbid conditions.