The Crux of Addiction Comorbidity: fMRI analysis of How Childhood Trauma Affects Network Functional Connectivity in the Comorbid Brain

Abstract

DUD co-occurring with other psychopathology (DCoP) is clinically prevalent, with up to 72% of patients treated for addiction having an additional mental health disorder. This dissertation sought to characterize functional neural network reorganization underlying DCoP compared to other psychopathology and its relationship to the developmental risk factor of childhood trauma. To better elucidate the relationship between childhood trauma, brain functional connectivity (FC), and DCoP, we hypothesized that functional neural network reorganization associated with childhood trauma induces a graded “susceptible” brain state that contributes to the development of drug use disorders (DUD) and multiple types of non-DUD mental health disorders (MHD), so that individuals who experience more severe traumatic experiences during childhood are more susceptible to developing psychopathology, including DCoP. We further hypothesized that DCoP is associated with modes of unique functional network reorganization that do not occur in individuals with either DUD or MHD alone, and that more extensive functional network reorganization underlying DCoP is associated with greater maladaptive behavior. In Chapter 1 we found that increased resting-state functional connectivity (rsFC) between the rostral anterior cingulate (rACC) and the temporoparietal junction (TPJ) uniquely distinguished a sample of trauma-exposed females with DCoP from trauma-exposed individuals with MHD, DUD, or no psychopathology. We then found for the DCoP sample that rsFC between subgenual cingulate and right anterior insula was related to severity of experienced physical abuse and negative self-criticism. In Chapter 2, we used dynamic causal modeling (DCM) to identify physical abuse-related alterations in DCoP circuitry underlying error processing and adaptation. Specifically, trauma-related FC from the left putamen to the left anterior insula was uniquely increased in DCoP females and acted on circuitry conferring post-error adaptive behavior. Finally, in Chapter 3 we developed a multivariate neural pattern classifier that accurately discriminated between rsFC of healthy comparison subjects and individuals with psychopathology, as well as between DCoP and other psychopathology. Using successive interrelated computational modeling approaches, we repeatedly show that severity of childhood trauma is closely tied to functional network reorganization underlying DCoP, and that increasing trauma severity is associated with greater changes in the DCoP brain.