Abstract
Substance use disorders (SUD) have been shown to be associated with gray matter (GM) loss, particularly in the frontal cortex. However, unclear is to what degree these regional GM alterations are substance-specific or shared across different substances, and if these regional GM alterations are independent of each other or the result of system-level processes at the intrinsic connectivity network level. The T1 weighted MRI data of 65 treated patients with alcohol use disorder (AUD), 27 patients with opioid use disorder (OUD) on maintenance therapy, 21 treated patients with stimulant use disorder comorbid with alcohol use disorder (polysubstance use disorder patients, PSU), and 21 healthy controls were examined via data-driven vertex-wise and voxel-wise GM analyses. Then, structural covariance analyses and open-access fMRI database analyses were used to map the cortical thinning patterns found in the three SUD groups onto intrinsic functional systems. Among AUD and OUD, we identified both common cortical thinning in right anterior brain regions as well as SUD-specific regional GM alterations that were not present in the PSU group. Furthermore, AUD patients had not only the most extended regional thinning but also significantly smaller subcortical structures and cerebellum relative to controls, OUD and PSU individuals. The system-level analyses revealed that AUD and OUD showed cortical thinning in several functional systems. In the AUD group the default mode network was clearly most affected, followed by the salience and executive control networks, whereas the salience and somatomotor network were highlighted as critical for understanding OUD. Structural brain alterations in groups with different SUDs are largely unique in their spatial extent and functional network correlates.
Highlights
Moderate to severe substance use disorder (SUD) is routinely associated with gray matter (GM) alterations, usually GM loss, in SUD individuals relative to controls [1,2,3] and with impairments in cognition and mood [4,5,6,7]
All three SUD subgroups scored higher than controls in amount and severity (AUDIT) of alcohol drinking
As the polysubstance use disorder (PSU) did not differ significantly from controls in regional Cortical Thickness (CT), and our planned follow-up analyses required the coordinates of the peak vertices of the two clusters with the most significant cortical thinning as input, we only report the following results for the alcohol use disorder (AUD) and opioid use disorder (OUD) groups
Summary
Moderate to severe substance use disorder (SUD) is routinely associated with gray matter (GM) alterations, usually GM loss, in SUD individuals relative to controls [1,2,3] and with impairments in cognition and mood [4,5,6,7]. A recent mega-analysis [2] compared cortical thickness and subcortical GM volume in 1,100 healthy controls and 2,140 SUD individuals using one of five different substances (alcohol, nicotine, cocaine, methamphetamine, or cannabis). Seven brain regions consisting of bilateral insula and middle temporal gyrus, left inferior parietal cortex, and supramarginal gyrus as well as right medial orbitofrontal cortex showed cortical thinning across all five SUDs; a common subcortical structure with GM volume loss, could not be identified [2]. In a follow-up study with a somewhat larger sample of 2,277 SUD individuals and 1,628 controls, the same authors used more fine-grained morphological shape analyses of subcortical GM structures to identify substance-specific and substancegeneral alterations in the same five SUD subgroups [1]. The authors did not find any subcortical shape alterations unique to the other three investigated SUD subgroups [1]
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