Gray and white matter morphology in substance use disorders: A neuroimaging systematic review and meta-analysis

Abstract

Substance use disorders (SUDs) are characterized by a compulsion to seek and consume one or more substances of abuse, with a perceived loss of control and negative emotional state. Repeated use of a substance results in synaptic and morphological changes, secondary to toxicity and SUD pathology in the dopamine striato-thalamo-cortical and limbic pathways. These neuroadaptations seem to vary between studies, which could be related to divergent effects of substances, consumption severity or other unknown factors. We therefore identified studies investigating the effects of SUDs using volumetric whole-brain voxel-based morphometry (VBM) in gray (GM) and white matter (WM). We performed a systematic review and meta-analysis of VBM studies using the anatomic likelihood estimation (ALE) method implemented in GingerALE (PROSPERO pre-registration CRD42017071222). Fifty studies met inclusion criteria and were included in the final quantitative meta-analysis, with a total of 538 foci, 88 experiments and 4370 participants. We found convergence and divergence in brain regions and volume effects (higher vs lower volume) in GM and WM depending on the severity of consumption pattern and type of substance. Convergent pathology was evident across substances in GM of the insula, anterior cingulate cortex, putamen, and thalamus, and in WM of the thalamic radiation and internal capsule bundle. Divergent pathology between occasional use (cortical pathology) and addiction (cortical-subcortical pathology) provides evidence of a possible top-down neuroadaptation. Our findings indicate distinctive brain morphometry alterations in SUDs, which may inform our understanding of disease progression and ultimately therapeutic approaches.MANUSCRIPT Pando-Naude, Victor Garza-Villarreal, Eduardo A.MANUSCRIPT Pando-Naude, Victor Garza-Villarreal, Eduardo A. 5 terms for articles published to the end of July 2018. No restrictions were placed on study design, but in order to be eligible for inclusion, the studies must have reported whole-brain VBM analyses. Screening and data extraction were performed using the Covidence tool 31 . The main outcome to extract was any change in gray and/or white matter analyzed using VBM, in stereotactic coordinates, comparing a substance user group and a healthy control group (details in Supplementary information). Quality assessment of MRI studies.Criteria for MRI quality reporting was selected from a set of guidelines for the standardized reporting of MRI studies [32][33][34] . Such guidelines dictate a more consistent and coherent policy for the reporting of MRI methods to ensure that methods can be understood and replicated. Analysis and meta-analytic technique.Statistically significant foci from between-group contrasts were extracted and recorded for each study. If necessary, coordinates were converted from Talairach coordinates to MNI space using the Lancaster transform (icbm2tal) incorporated in GingerALE (www.brainmap.org/). All metaanalyses were performed using anatomic likelihood estimation (ALE), implemented ...

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

“…Finally, it should be noted that the results of our analysis are not consistent with those of another recent meta-analysis 26 , where a pattern of convergent WM volumetric alterations in AUD in the corticospinal tract and anterior thalamic radiation has been identified. However, this meta-analysis was not explicitly designed to investigate WM alterations in AUD but reported respective findings as a part of a subanalysis in a broader context based on four studies only.…”

“…This is possible because the ALE method itself tests directionally independent since it is not based on effect sizes 28 , which is particularly useful in the context of clinical samples, where the effects may vary over the course of the disorder (e.g. as a function of the duration of abstinence or changes in the proportion of grey to white matter) 23,26 . A close inspection of the contributing foci revealed that the ALE convergence clusters identified in our meta-analysis are largely based on studies that report a WM reduction in AUD patients.…”

“…This important work showed small to moderate effect sizes (g = .304, SD = 0.134) but did not test for convergence of imaging results in order to draw conclusions about the location of altered WM in AUD. A recent large-scale meta-analysis focused on gray and white matter morphology across all substance use disorders and indicates general and substance-specific structural brain changes in patients compared with healthy controls 26 . Sub-analysis regarding AUD in specific revealed convergent WM alterations in regions of the corticospinal tract and anterior thalamic radiation.…”

Disrupted functional connectivity of the brain reward system in substance use problems: a meta-analysis of functional neuroimaging studies

“…In line with these findings, studies using structural imaging method found that grey matter deficits in subjects with SUDs are not restricted to regions implicated in the brain reward system (e.g. striatum and vmPFC/mOFC), and are also frequently observed in the anterior insula, thalamus, ACC and the amygdala 18-21 . Finally, in functional brain connectivity studies (both task-based and resting-state modalities), researchers found impaired connectivity between brain regions of the reward system in individuals with SUDs 22 , with possible alterations in other brain networks such as the frontoparietal and the default-mode networks 23-25 .…”

Common and distinct cortico-striatal volumetric changes in cocaine and heroin use disorder

“…. In an opposite direction but still common to drug-addicted individuals (i.e., spanning different drug classes), volumetric increases have been reported for the dorsal striatum (15) that regulates habit formation (16,17), potentially related to its dopaminergically-mediated role in cue sensitivity and craving (18).…”