Varieties of Impulsivity in Opiate and Stimulant Users

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Project Summary Impulsivity has gained prominence as one of the cardinal etiological risk factors for the development and maintenance of addictive disorders. However, both impulsivity and addiction are highly heterogeneous, which has hampered progress in understanding the link between the two. To address this heterogeneity, we have developed a program of addiction research in Bulgaria, a major European center for production of synthetic amphetamine-type stimulants and a key transit country for heroin trafficking, due to its strategic geographical position on the Balkan Drug Route. Through our 17-yearlong collaboration with Bulgarian colleagues, we have accessed rare populations of predominantly monosubstance-dependent (‘pure’) heroin and amphetamine users, many in protracted abstinence. In the parent DA021421 study, we have tested >800 participants with a comprehensive assessment battery of clinical, personality, and neurocognitive tasks of impulsivity and related externalizing and internalizing phenotypes. We genotyped participants with the Smokescreen array and enrolled siblings discordant for opiate and stimulant addictions. We combined theory-driven (e.g. cognitive modeling, joint modeling) with data-driven (e.g. machine learning (ML)) computational approaches, which proved particularly informative and revealed distinct multivariate risk profiles characterizing opiate and stimulant addictions with high degree of accuracy. Findings from the parent study significantly informed our integrative multidisciplinary framework (Vassileva & Conrod, 2019), which highlights the potential for distinct dimensions of impulsivity to inform clinical assessment and intervention development for different types of addictions. Impulsivity also figures prominently in the neuroscience-based heuristic framework for the neuroclinical assessment of addictions (ANA; Kwako et al., 2016), which proposes that successful addiction treatment must accommodate the heterogeneity and different etiological mechanisms implicated in addictions, by performing multidimensional assessments focusing on three neurofunctional domains of impulsivity and compulsivity: executive function (EF), incentive salience (IS), and negative emotionality (NE). However, because the ANA framework is based primarily on findings in alcohol use disorder, it is not well understood how these domains might generalize to other SUD, such as opiate and stimulant use disorders. The current competing renewal application aims to address this critical gap with the following specific aims: Aim 1: Identify key personality, neurobehavioral, polygenic, and computational markers of opiate and stimulant addiction following the ANA framework, using the comprehensive assessment battery and computational methods developed in the parent DA021421 with 250 participants (100 with opiate use disorder, 100 with stimulant use disorder, and 50 healthy controls); Aim 2: Identify the brain signatures of the 3 ANA domains (EF, IS, NE) in opiate and stimulant addictions; Exploratory Aim 3: Combine data from Aims 1 and 2 to identify addiction biotypes based on neurocircuitry implicated in the ANA domains.