Linking affective symptoms and brain morphology in cocaine use disorder: An integrated network approach

Background: Cocaine use disorder (CUD) often co-occurs with depressive and anxiety symptoms, suggesting shared neurobiological bases. This study aimed to understand the relationship between these heterogeneous individual symptoms and structural brain characteristics in CUD using an integrated network approach. Method: Data from 116 individuals (17 women) with CUD (SUDMEX project) were analyzed. We used item-level depression and anxiety scores from the SCL-90-R, along with measures of cortical thickness (insula, inferior/middle frontal gyrus, anterior cingulate cortex) and hippocampal volume. Four brain-behavior integrated networks were estimated: (1) brain regions with depressive symptoms, (2) brain regions with anxiety symptoms, (3) brain regions with global depression scores, and (4) brain regions with global anxiety scores. Results: The symptom-level networks revealed specific associations. The insula was a central finding, showing negative associations in the depression network with Crying (partial r = −0.078) and Self-blame (partial r = −0.024), and in the anxiety network with Being/Feeling Scared (partial r = −0.058). Furthermore, insular thickness was negatively associated with the global depression score (partial r = −0.068). These associations were not moderated by duration of cocaine use. Conclusions: The findings identify the insula as a potential neural hub linking affective symptoms with brain morphology in CUD. This integrated approach offers a more nuanced understanding of the complex relationships between psychiatric symptoms and brain structure in CUD.