Cingulate cortical thickness in cocaine use disorder: mediation effect between early life stress and cocaine consumption.

Objective: The cingulate gyrus is implicated in the neurobiology of addiction, such as chronic cocaine consumption. Early life stress (ELS) is an important moderator of cocaine use disorder (CUD). Therefore, we investigated the effect of CUD on cingulate cortical thickness and tested whether a history of ELS could influence the effects of CUD.

Methods: Participants aged 18-50 years (78 with CUD due to crack cocaine consumption and 53 healthy controls) underwent magnetic resonance imaging and the cingulate thickness (rostral anterior, caudal anterior, posterior, and isthmus regions) was analysed. The clinical assessment comprised the Childhood Trauma Questionnaire (CTQ) and the Addiction Severity Index. Group comparisons adjusting by sex, age, and education were performed. Mediation models were generated where lifetime cocaine use, CTQ score, and cortical thickness corresponded to the independent variable, intermediary variable, and outcome, respectively.

Results: Group comparisons revealed significant differences in six out of eight cingulate cortices, showing lower thickness in the CUD group. Furthermore, years of regular cocaine use was the variable most associated with cingulate thickness. Negative correlations were found between CTQ scores and the isthmus cingulate (right hemisphere), as well as with the rostral anterior cingulate (left hemisphere). In the mediation analysis, we observed a significant negative direct effect of lifetime cocaine use on the isthmus cingulate and an indirect effect of cocaine use mediated by CTQ score.

Conclusion: Our findings suggest that a history of ELS could aggravate the negative effects of chronic cocaine use on the cingulate gyrus, particularly in the right isthmus cingulate cortex.