A coordinate-based meta-analysis of white matter alterations in patients with alcohol use disorder

Abstract

Introduction: Besides the commonly described gray matter (GM) deficits, there is growing evidence of significant white matter (WM) alterations in patients with alcohol use disorder (AUD). WM changes can be assessed using volumetric and diffusive magnetic resonance imaging methods, such as voxel-based morphometry (VBM) and diffusion tensor imaging (DTI). The aim of the present meta-analysis is to investigate the spatial convergence of the reported findings on WM alterations in AUD. Methods: Systematic literature search on PubMed and further databases revealed 18 studies eligible for inclusion, entailing a total of 462 AUD patients and 416 healthy controls (up to January 18, 2021). All studies that had used either VBM or DTI whole-brain analyzing methods and reported results as peak-coordinates in standard reference space were considered for inclusion. We excluded studies using approaches non-concordant with recent guidelines for neuroimaging meta-analyses and studies investigating patient groups with Korsakoff syndrome or other comorbid substance use disorders (except tobacco). Results: Anatomical likelihood estimation (ALE) revealed four significant clusters of convergent macro- and microstructural WM alterations in AUD patients that were assigned to the genu and body of the corpus callosum, anterior and posterior cingulum, fornix, and the right posterior limb of the internal capsule. Discussion: The changes in WM could to some extent explain the deteriorations in motor, cognitive, affective, and perceptual functions seen in AUD. Future studies are needed to clarify how WM alterations vary over the course of the disorder and to what extent they are reversible with prolonged abstinence.

Alterations in white matter microstructure in alcohol and alcohol‐polydrug dependence: Associations with lifetime alcohol and nicotine exposure

“…In line with our primary hypothesis, we found lower FA in AD across the corpus callosum and extending into parts of the corona radiata. These findings are consistent with a recent meta‐analysis of white matter in AD highlighting convergent macro‐ and microstructural WM alterations in the corpus callosum 13 . We demonstrated that callosal effects are negatively associated with long‐term excessive alcohol consumption.…”

“…These findings are consistent with a recent meta-analysis of white matter in AD highlighting convergent macro-and microstructural WM alterations in the corpus callosum. 13 We demonstrated that callosal effects are negatively associated with long-term excessive alcohol consumption. The anterior corpus callosum has been highlighted as a vulnerable region to the effects of alcohol, and a negative association with consumption has been shown in a cohort of adult alcohol drinkers.…”

“…TBSS studies of AD have frequently reported lower FA in the corpus callosum, 5–12 with mixed findings implicating other tracts and regions. A meta‐analysis of white matter macro‐ and microstructural differences in AD further confirmed that alterations converge on the corpus callosum, cingulum bundle and internal capsule 13 . Considering only the 11 identified DTI studies, differences were solely found along the corpus callosum and fornix.…”

“…A meta-analysis of white matter macro-and microstructural differences in AD further confirmed that alterations converge on the corpus callosum, cingulum bundle and internal capsule. 13 Considering only the 11 identified DTI studies, differences were solely found along the corpus callosum and fornix. It is important to note that though most studies have examined recently abstinent patients, [5][6][7][8][9][10] similar disturbances in the corpus callosum have been found in long-term abstinent 8 and non-treatment-seeking patients.…”

Intracortical myelin in individuals with alcohol use disorder: An initial proof‐of‐concept study

“…Global deficits in white matter volume have been reported in numerous studies, as confirmed by a meta‐analysis of 19 studies with over 1300 participants (Monnig et al., 2013 ). A coordinate‐based meta‐analysis of 18 studies reported macro‐ and microstructural WM alterations in patients with AUD that were assigned to the genu and body of the corpus callosum, anterior and posterior cingulum, fornix, and the posterior limb of the internal capsule (Spindler et al., 2022 ). Evidence for disrupted myelin in AUD includes postmortem studies reporting demyelination in humans with a history of AUD and irregular folding and splitting of myelin membranes (Rice & Gu, 2019 ).…”