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Generalized and specific whole-brain white matter abnormalities in human cocaine and heroin use disorders

Neuroimaging studies in substance use disorder have shown widespread impairments in white matter (WM) microstructure suggesting demyelination and axonal damage. However, substantially fewer studies explored generalized vs. acute/specific drug effects on WM. Our study assessed whole-brain WM integrity in three subgroups of addicted individuals, encompassing cocaine (CUD) and heroin (HUD) use disorder, compared to healthy controls (CTL). Diffusion MRI was acquired in 58 CTL, 28 current cocaine users/CUD+, 32 abstinent cocaine users/CUD-, and 30 individuals with HUD (positive urine for cocaine in CUD+ and opiates used for treatment in HUD). Tract-Based Spatial Statistics allowed voxelwise analyses of diffusion metrics [fractional anisotropy/FA, mean diffusivity/MD, radial diffusivity/RD, and axial diffusivity/AD]. Permutation statistics (p-corrected<.05) were used for between-group t-tests. Compared to CTL, all drug-addicted individuals showed widespread FA reductions, and increased MD, RD, and AD (19-57% of WM skeleton, p<.05). The HUD showed the most impairments, followed by the CUD+, with only minor FA reductions in CUD- (<.2% of skeleton, p=.05). Longer periods of regular use were associated with decreased FA and AD, and higher subjective craving was associated with increased MD, RD, and AD, across all drug-addicted individuals (p<.05). These findings demonstrate extensive WM impairments in drug-addicted individuals characterized by decreased anisotropy and increased diffusivity, thought to reflect demyelination and lower axonal packing. Extensive abnormalities in both groups with positive urine status (CUD+ and HUD), and correlations with craving, suggest greater WM impairments with recency of use. Results in CUD-, and correlations with regular use, further imply cumulative and/or persistent WM damage.