Neuroclinical Framework for the Role of Stress in Addiction

Addiction has been conceptualized as a three-stage cycle—binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation—that worsens over time and involves allostatic changes in hedonic function via changes in the brain reward and stress systems. Using the withdrawal/negative affect stage and negative reinforcement as an important source of motivation for compulsive drug seeking, we outline the neurobiology of the stress component of the withdrawal/negative affect stage and relate it to a derivative of the Research Domain Criteria research construct for the study of psychiatric disease, known as the Addictions Neuroclinical Assessment. Using the Addictions Neuroclinical Assessment, we outline five subdomains of negative emotional states that can be operationally measured in human laboratory settings and paralleled by animal models. We hypothesize that a focus on negative emotionality and stress is closely related to the acute neurobiological alterations that are experienced in addiction and may serve as a bridge to a reformulation of the addiction nosology to better capture individual differences in patients for whom the withdrawal/negative affect stage drives compulsive drug taking.