Brain structural differences in cocaine use disorder: Insights from multivariate and neurotransmitter analyses

Cocaine use disorder (CUD) is a chronic and relapsing neuropsychiatric disorder characterized by structural and functional brain lesions, posing a significant public health challenge. While the disruptive effects of cocaine on neurotransmitter systems (receptors/transporters) have been well established, the patterns of brain structural abnormalities in CUD and its interaction with other factors remain an ongoing topic of investigation. We employed source-based morphometry (SBM), a multivariate approach on 50 CUD participants and 50 matched healthy controls from the public SUDMEX CONN dataset. This method allowed us to identify co-varying patterns of brain tissue volume differences, and further explore the effect of average cocaine dosage through moderation analysis. Spatial correlation analysis was also performed to examine micro-macro structural consistency between tissue volume variations and chemoarchitectural distribution of dopamine and serotonin. Our SBM analysis findings were consistent with reward-related neuroadaptations in the striato-thalamo-cortical and limbic pathways and also exhibited co-localization with the distribution of dopamine and serotonin systems. The moderation analysis suggested that the average dosage positively strengthens cocaine consumption years' effect on brain structures. By integrating our findings of gray and white matter volume differences and corresponding neurotransmitter profiles, this comprehensive view not only strengthens our understanding of the brain's structural abnormalities in CUD, but also reveals potential mechanisms underlying its development and progression.