White matter microstructure alterations from alcohol use disorder persist into early abstinence

Abstract Alcohol use disorder (AUD) is a complex condition including affective, cognitive and motivational dimensions. Although AUD is known to induce diffuse brain damage, including grey matter shrinkage and ventricular enlargement, the microstructural changes it induces in white matter remain incompletely understood. This study leverages multi-shell diffusion MRI and multi-fixel models to (i) undertake whole-brain and tract-specific analyses to investigate the microstructure of white matter (WM) tracts affected by AUD, (ii) evaluate whether these differences persist in early abstinence, and (iii) correlate these results with clinical measures evaluated by validated psychological questionnaires. We recruited a final cohort of 37 AUD patients, admitted for alcohol withdrawal and selected for their ongoing alcohol consumption at the time of admission, and a demographically matched control group of 19 healthy subjects. Both groups underwent MRI scans at baseline and 18 days later, with assessments of depression, obsession-compulsion, and anxiety conducted in both sessions for the AUD patients and once for the control group. The imaging results confirmed the presence in AUD participants of clusters microstructural alterations in the fornix, corpus callosum, cingulum, uncinate fasciculus and anterior thalamic radiations. These white matter tracts presented global and localized microstructural changes in axial diffusivity and fractional anisotropy, which are linked to axonal damage and inflammation. There was no significant improvement in the diffusion metrics after almost three weeks of abstinence, although clinical measures did improve significantly. Depression scores were significantly elevated in the patients at admission and decreased with time. Depression scores before withdrawal showed correlations with microstructural metrics across the right anterior thalamic radiations, the isthmus of the corpus callosum, and the right uncinate fasciculus. Lower fractional anisotropy and higher radial diffusivity were predictive of higher depression scores. Overall, these findings highlight the long-term vulnerability of WM tracts affected by AUD and the link between tract microstructure, brain function and behavior.