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

Drugs of abuse impact cortico-striatal dopaminergic targets and their morphology across substance types in common and unique ways. While the dorsal striatum drives 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 in individuals with cocaine or heroin use disorder (CUD/HUD): decreased GMV of vmPFC/NAcc in HUD and IFG in CUD, and putamen GMV to be associated with addiction severity. We quantified GMV in age/sex/IQ-matched individuals with CUD (n=20; 5 women), HUD (n=20; 6 women), and healthy controls (HC; n=20; 5 women), further replicated in an extended sample (combined n=96). Overall, addicted individuals had smaller vmPFC volumes than HC ( p <0.05-corrected), driven by HUD ( p <0.05-corrected; similar NAcc reduction). Right IFG reductions were specifically evident in CUD vs. HUD ( p <0.05-corrected). Posterior putamen volume increased as a function of craving in CUD vs. HUD (p<0.05-corrected). These results indicate compression of dopamine-innervated regions (in the vmPFC and NAcc) across cocaine- or heroin-addicted individuals, more severely in the latter. For the first time we demonstrate IFG compression specifically in CUD. This group also showed a unique association between craving and increased putamen volume, together indicating a signature of enhanced cue-sensitivity and habit formation. Results suggest common and substance-specific morphometry volumetric changes in human psychostimulant or opiate addiction, with implications for fine-tuning biomarker and treatment identification by primary drug of abuse.