Neurophysiological Correlates and Differential Drug Response in Subjects With a Family History of an Alcohol Use Disorder

Abstract

A family history of an alcohol use disorder (AUD) has been shown to increase one’s risk of developing an AUD. Additionally, a positive family history of AUD (family history positive (FHP)) has neurobiological and neuropsychopharmacological consequences, and this review summarizes differential drug response as well as neuroanatomical and neurocognitive correlates. FHP status is related to altered responses to a number of drugs, including substances with abuse liability like alcohol, opioids, amphetamines, and ketamine. FHP individuals demonstrate fewer aversive effects and more rewarding response to both alcohol and subanesthetic dose ketamine. Ketamine is a rapid-acting antidepressant, and several studies have reported that ketamine is more effective for FHP treatment-resistant depressed individuals. In short, the reviewed neurophysiological differences may contribute to ketamine’s enhanced antidepressant efficacy in FHP patients. Volumetric differences in the amygdala, nucleus accumbens, neocortex, and cerebellum are commonly reported. Furthermore, FHP has also been associated with altered neurocognitive performance, e.g., increased impulsivity. The imaging and psychological literature supports a neurodevelopmental lag hypothesis in FHP youth. The review will further discuss these findings in depth.