Abstract
AbstractAnimal models have shown that chronic alcohol exposure is associated with persistent neuroadaptations in amygdala synaptic function, whereas human studies have consistently reported amygdala grey‐matter volume (GMV) reductions in alcohol dependent patients (ADP). We hypothesised that chronic alcohol use associated with neuroadaptations may entail a reconfiguration of the amygdala's functional interactions and that these mechanisms may be affected by structural atrophy. We compared amygdala resting state functional connectivity (RSFC) using a whole brain seed‐based approach and amygdala GMV in abstinent ADP (n = 20) and healthy controls (HC; n = 39), balanced for age, gender and levels of head motion. The potential moderating influence of age, cumulative alcohol exposure, abstinence length and head motion was further examined in the two groups separately using correlational analyses. We found increased amygdala RSFC with substantia nigra/ventral tegmental area (SN/VTA) in ADP compared with HC. As expected, amygdala GMV was lower in ADP. Multiple regression analyses of the ADP group showed that amygdala‐SN/VTA RSFC increases were primarily associated with cumulative alcohol exposure rather than age, whereas amygdala GMV reductions were primarily associated with age rather than cumulative alcohol exposure. The same association between age and amygdala GMV was not observed amongst HC. Importantly, amygdala GMV and amygdala‐SN/VTA RSFC were uncorrelated in ADP, and neither measure was correlated with abstinence length. These results suggest that chronic alcohol exposure is associated with persistent elevations in amygdala‐SN/VTA RSFC and accelerated age‐related grey‐matter atrophy through potentially distinct mechanisms.
Highlights
Chronic, excessive alcohol consumption is associated with widespread homeostatic neuroadaptations, whose effects become unmasked during withdrawal as intense autonomic and emotional disturbances, which in turn negatively reinforce alcohol consumption.[1]
This study examined amygdala resting state functional connectivity (RSFC) and grey-matter volume (GMV) in 20 alcohol dependent patients (ADP) and 39 healthy controls (HC)
3.1 | Amygdala-substantia nigra/ventral tegmental area RSFC is positively correlated with cumulative alcohol exposure
Summary
Excessive alcohol consumption is associated with widespread homeostatic neuroadaptations, whose effects become unmasked during withdrawal as intense autonomic and emotional disturbances, which in turn negatively reinforce alcohol consumption.[1]. To our knowledge, no study has explored chronic alterations in amygdala RSFC with reference to cumulative alcohol exposure in abstinent alcohol-dependent patients. There is evidence that alterations in RSFC in substance-dependent populations may be related to structural atrophy.[13,14] Smaller amygdala grey-matter volume (GMV) is widely documented in alcohol dependent populations (ADP) and[15,16,17,18] is associated with a greater likelihood of relapse,[16] yet its relationship to amygdala RSFC has not been investigated. Because animal models implicate multiple effector regions which may be chronically modulated by local neuroadaptations in the amygdala,[7] we applied a whole brain approach to our RSFC analyses.
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