Integrative Epigenomic Mapping of Co-Morbid OUD and PTSD

项目总结

Project Summary Opioid use disorder (OUD) often co-occurs with post-traumatic stress disorder (PTSD), particularly in the veteran population. People with comorbid OUD and PTSD (OUD+PTSD) exhibit worse health and physical outcomes and poor treatment response. Previous studies have found that dopaminergic signaling (DAergic) within the prefrontal cortex (PFC) plays a key role in the modulation of the cognitive and affective effects of stress exposure (i.e., PTSD) in opioid abuse vulnerability. PFC neuronal modulation involved in drug abuse and stress response may be mediated by epigenetic mechanisms. PAS-18-625 calls for research to investigate the mechanisms of psychosocial stress on opioid use patterns. In this study, we hypothesize that the PFC’s modulatory role on cognitive and affective effects of comorbid OUD+PTSD may be mediated by epigenetic mechanisms. For this, we will examine neuron-specific epigenetic profiles within the DAergic system and at a genome-wide level, in postmortem PFC of people with comorbid OUD+PTSD. A total of 48 postmortem brain samples from the Veteran Affair’s National PTSD Brain Bank (VA-NPBB) will be examined. We will investigate the methylome, hydroxymethylome, and transcriptome in the context of comorbid OUD+PTSD and will integrate the different –omics datasets generated to identify gene networks associated with these disorders. This study will increase our understanding on the biological mechanisms that underlie comorbid OUD+PTSD needed to uncover novel targets for preventative, prognostic, and treatment efforts.