Resting state synchrony in anxiety-related circuits of abstinent alcohol-dependent patients

Background: Anxiety has been linked to initiation, maintenance and relapse of alcohol dependence. Neurobiological models of anxiety have proposed important roles for amygdala-insula and amygdala-medial prefrontal cortex interactions in the generation and regulation of anxiety states, respectively. Objectives: This study tested the hypotheses that abstinent alcohol-dependent patients would show a disruption of synchrony in these circuits as measured by resting state functional MRI. Methods: The study examined recently abstinent (n = 13), longer-term abstinent (n = 16) alcohol-dependent patients and healthy controls (n = 22). Resting-state synchrony (RSS) was examined in specific circuits, where degree of synchrony has been found to correlate with state anxiety levels in previous studies. Results: Alcohol-dependent patients showed significantly elevated scores on anxiety and depression inventories compared with controls. No significant group differences in synchrony were observed between right amygdala and right ventromedial prefrontal cortex (vmPFC), between left amygdala and left vmPFC, or, after correction for multiple comparisons, right amygdala and dorsomedial prefrontal cortex (dmPFC). However, significantly decreased positive synchrony was found between left basolateral amygdala and left anterior insula, in patients relative to controls. Conclusion: Both early and longer-term abstinent alcohol-dependent patients showed increased anxiety levels relative to controls and altered resting state synchrony in circuits previously linked to state anxiety. Notably, the significant group differences in synchrony were in the opposite direction to our predictions based on the literature. These results may point to a lack of generalizability of models derived from young healthy homogeneous samples.