Applying the Addictions Neuroclinical Assessment to derive neurofunctional domains in individuals who use methamphetamine.

The Addictions Neuroclinical Assessment (ANA) was proposed as a neuroscience-informed clinical framework to understand heterogeneity in addiction encompassing dysfunction in three domains: incentive salience, negative emotionality, and executive functions. The ANA has been validated in the alcohol field but has not been extended to other substances. Thus, the objective of the current study was to replicate and extend the ANA framework to methamphetamine use disorder. Non-treatment seeking individuals (N = 185) who reported regular methamphetamine use completed a deep phenotyping battery comprising self-report and behavioral measures that assessed methamphetamine craving and emotional withdrawal symptoms, mood and anxiety symptomatology, risk-taking behaviors, working memory, attention, and impulsivity. Factor analytic techniques were used in an iterative manner to derive latent factors that explained biobehavioral variation in the sample. The relationship between factor scores and demographic and clinical indicators of methamphetamine use were examined to assess the construct validity of the latent factors. Deep phenotyping combined with factor analytic techniques implicated three intercorrelated neurofunctional domains that map on to the proposed ANA domains: incentive salience, negative emotionality, and executive function. Each of the domains were associated with demographic and clinical indicators of methamphetamine use providing initial support for their construct validity. The ANA framework holds promise for explaining heterogeneity in addiction by identifying neuroscience-informed phenotypes. Knowledge from the ANA framework may be applied to advance precision medicine and inform medications development for a host of substance use disorders, particularly those with no approved pharmacotherapy such as methamphetamine.