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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.

Substance-Specific and Shared Gray Matter Signatures in Alcohol, Opioid, and Polysubstance Use Disorder