Common and distinct fronto-striatal volumetric changes in heroin and cocaine use disorders.

Different drugs of abuse impact the morphology of fronto-striatal dopaminergic targets in both common and unique ways. While dorsal striatal volume tracks with addiction severity across drug classes, opiates impact ventromedial prefrontal cortex (vmPFC) and nucleus accumbens (NAcc) neuroplasticity in preclinical models, and psychostimulants alter inhibitory control, rooted in cortical regions such as the inferior frontal gyrus (IFG). We hypothesized parallel gray matter volume (GMV) changes associated with human heroin or cocaine use disorder (HUD/CUD): lower GMV of vmPFC/NAcc in HUD and IFG in CUD, and putamen GMV to be associated with addiction severity measures (including craving) across both. In this cross-sectional study, we quantified GMV (p < 0.05-corrected) in age/sex/IQ-matched individuals with HUD (n = 32; 7 women), CUD (n = 32; 6 women), and healthy controls (HC; n = 32; 6 women) and compared fronto-striatal volume between groups using voxelwise general linear models and non-parametric permutation based tests. Overall, individuals with HUD had smaller vmPFC and NAcc/putamen volumes than HC. Bilateral lower IFG GMV patterns were specifically evident in CUD vs. HUD. Correlations between addiction severity measures and putamen GMV did not reach nominal significance level in this sample. These results indicate alterations in dopamine-innervated regions (in the vmPFC and NAcc) in heroin addiction. For the first time we demonstrate lower IFG GMV specifically in CUD as compared to HUD, suggesting a signature of reduced inhibitory control, which remains to be tested directly using select behavioral measures. Overall, results suggest substance-specific volumetric changes in human psychostimulant or opiate addiction, with implications for fine-tuning biomarker and treatment identification by primary drug of abuse.