Polygenic risk and childhood adversity as moderators of drug and alcohol withdrawal symptoms.

Abstract

Reducing or stopping substance use can result in withdrawal symptoms in physically dependent individuals. Appropriate management of withdrawal symptoms may be critical to the safety of individuals with substance use disorders (SUDs) and could help prevent a return to substance use. Although childhood adversity and genetic factors contribute to the development of SUDs, their individual and joint effects on withdrawal symptoms and severity are less clear. This study is a secondary analysis of existing data in which we examined the main and interactive effects of genetic variation and adverse childhood events (ACEs) on the severity of withdrawal from tobacco, alcohol, and opioids. Participants were 10,275 individuals (4851 of African-like (AFR) ancestry and 5424 of European-like (EUR) ancestry) from the Yale-Penn sample. Tobacco, alcohol, and opioid withdrawal symptoms and 10 ACEs were measured using a semi-structured diagnostic instrument. Multivariate regression models examined the association of SUD polygenic scores (PGS), ACEs, and their interaction with withdrawal severity and individual withdrawal symptoms. ACEs were positively associated with withdrawal severity, except for opioid withdrawal among AFR individuals. Among EUR individuals, PGS were positively associated with tobacco and alcohol withdrawal severity. There was a negative interaction between ACEs and PGS on tobacco withdrawal severity and specific tobacco withdrawal symptoms. Individuals who experience ACEs and, to a lesser extent, those with higher PGS for SUDs, are susceptible to more severe withdrawal symptoms. In EUR individuals, there was evidence for a complex interplay of genetic and environmental factors on substance withdrawal. These exploratory findings require independent validation.