The neural representation of the association between comorbid drug use disorders and childhood maltreatment

Background: Comorbidity of drug use disorders (DUD) with other psychopathology is associated with worse functional and treatment outcomes than DUD alone. The present study sought to identify altered functional neural circuitry underlying DUD comorbidity with other psychiatric disorders, and model the relationship of these alterations to childhood trauma (Childhood Trauma Questionnaire) and negative self-beliefs (Beck Depression Inventory). Methods: A sample of adult men and women (mean = 36.8 years) with childhood maltreatment histories (n = 81) was allocated into the following groups based on psychiatric diagnoses and drug use history: no current or past psychiatric disorders (trauma control sample, n = 20), DUD only (n = 22), psychopathology only (n = 20), and DUD comorbid with other psychiatric illness (DCoP, n = 25). Results: Multiple regression of seed-based resting-state fMRI, controlling for age and sex, identified a functional connection between the right rostral anterior cingulate cortex (rACC) and left temporoparietal junction (TPJ) that was significantly increased in DCoP females, relative to the other clinical and control groups. Within the DCoP female sample, mediation analysis demonstrated that strength of connectivity between the subgenual cingulate cortex and both the right anterior insula and rostral lateral prefrontal cortex significantly mediated the relationship between increasing physical abuse and self-criticism with age as a moderator. Conclusions: This study related sex-dependent alterations in functional organization of the prefrontal cortex with DCoP that are, in turn, related to magnitude of negative self-beliefs to childhood trauma exposure. Additionally, DCoP-selective alterations in rACC connectivity suggest that the neural correlates of DCoP do not represent linear additive contributions from two independent disorders.