New Study Explores How Childhood Adversity and Genetics Influence Withdrawal Symptoms in Substance Use Disorders

A new study published in Drug and Alcohol Dependence examined the relationship between childhood adversity, genetic risk, and the severity of withdrawal symptoms from tobacco, alcohol, and opioids. The study used data from more than 10,000 participants collected through a multi-site collaboration across academic institutions, including Yale University, UConn Health, the University of Pennsylvania, the Medical University of South Carolina, and McLean Hospital.

“ACEs are an important risk factor for the development of SUD, and assessing for them can assist healthcare providers in better treating patients," says Dr. Redonna Chandler, former Director of HIV Research Program (HRP) at the National Institute on Drug Abuse and current member of the Addiction Policy Forum’s Scientific Advisory Board. "Additionally, new information regarding the potential connection between ACEs and withdrawal severity could also be important in tailoring treatment to better meet the needs of patients.”

Researchers assessed how ACEs and polygenic risk scores (PGS) — a measure of genetic vulnerability — were associated with withdrawal severity in individuals with African and European ancestry. ACEs included exposures such as physical abuse, neglect, and household substance use before age 18. PGS were derived from genome-wide association studies related to substance use traits. The analysis focused on withdrawal symptoms reported during tobacco, alcohol, or opioid cessation, including anxiety, irritability, insomnia, and cravings.

Key Findings

• ACEs were associated with more severe withdrawal symptoms for individuals of African ancestry for tobacco and alcohol.

• For individuals with European ancestry, genetic risk was also associated with withdrawal severity, particularly for alcohol and tobacco.

• ACEs were more strongly associated with withdrawal severity than polygenic risk scores.

• Individuals who experienced severe withdrawal from one substance were also more likely to report intense symptoms when withdrawing from other substances, indicating shared underlying biological, psychosocial, or environmental risk factors.

• Tobacco withdrawal showed the strongest association with both ACEs and PGS in both individuals with African and European ancestry, followed by alcohol for individuals with European ancestry. Although opioid withdrawal symptoms were reported more frequently overall, they showed fewer associations with either ACEs or genetic risk.

• The associations of ACEs and PGS with withdrawal severity and symptoms differed across substances and ancestry groups.

Adverse childhood experiences may be important to consider in evaluating withdrawal risk and planning treatment, noted the authors. They also acknowledge several limitations, including reliance on self-reported withdrawal symptoms and a genetic sample composed primarily of individuals of European ancestry. Additional research is needed to examine these associations in more diverse populations and across a broader range of substances.

Because this study was a secondary analysis of existing data with eligibility requirements based on level of substance use, certain potentially relevant variables—such as duration of substance use—were not controlled for. The authors acknowledge these constraints and emphasize the need for replication using prospective designs and more diverse samples.

Read More

The Article

Han, A., Davis, C. N., Jinwala, Z., SooHoo, J., Gelernter, J., Feinn, R., & Kranzler, H. R. (2025). Polygenic risk and childhood adversity as moderators of drug and alcohol withdrawal symptoms. Drug and Alcohol Dependence, 273, 112712. https://doi.org/10.1016/j.drugalcdep.2025.112712