Neurocircuitry of clinical insight predicting relapse outcomes in opioid addiction

PROJECT SUMMARY Impaired self-awareness of illness severity (insight) is associated with increased morbidity and poorer treatment outcome across multiple neuropsychiatric diseases. Although the study of insight has traditionally been limited to psychotic disorders (e.g., schizophrenia, mania), emerging theory and evidence suggest that this construct may also be highly relevant to drug addiction. For example, drug-addicted individuals often overestimate their addiction-related self-control, underestimate their neurocognitive impairments, and often do not perceive a need for treatment despite the pervasive consequences precipitated by their drug use. For individuals with opioid use disorder (OUD) especially, because first-line treatment often involves medication- assisted therapy that must be taken for long and indefinite periods of time, a strong and sustained personal engagement with treatment is required to prevent relapse (which is the norm, not the exception). In this R01 application, we undertake the first systematic investigation of insight and its underlying neural circuitry as biomarkers and longitudinal predictors of relapse and treatment adherence in individuals with OUD. Recently- detoxified and medication-maintained OUD participants (primary drug: heroin) and matched healthy controls (HC) will complete a novel functional magnetic resonance imaging (fMRI) ‘insight’ task, during which they respond to statements about the severity of their drug use and perceived need for behavior change. Specific Aims include uncovering the behavioral and neural correlates of drug-related insight in OUD, and examining the ability of this circuitry (A) to predict future opioid use and (B) to recover functioning over time with abstinence. We hypothesize that lower opioid use and better treatment adherence (avoiding relapse) will be linked with more intact baseline functioning, and more improvements in functioning from baseline to 6-month follow-up, of the rostral anterior cingulate cortex extending into the ventromedial prefrontal cortex (rACC/vmPFC). This rACC/vmPFC region, insofar as it mediates personal relevance in health and is disrupted in drug addiction (and other psychopathologies), provides a plausible and a priori candidate region for studying insight circuitry. If the anticipated relationships are observed, our results will shed light on a critical construct in OUD – and in drug addiction, more generally – that has the potential to perpetuate drug use, but that to date has a very lean tradition of empirical study, especially with regard to underlying brain mechanisms. A better understanding of this circuitry can suggest novel treatment targets for increasing treatment adherence in OUD, which in turn can be beneficial for addressing the current opioid epidemic.