Influence of early adversity on cortisol reactivity, SLC6A4 methylation and externalizing behavior in children of alcoholics

Abstract Background Children of parents with alcoholism face considerable stress, and often have externalizing behaviors. Early adversity is known to affect DNA methylation and the functioning of the HPA axis. We investigated the association of early adversity with cortisol reactivity, 5HTTLPR genotype, site specific DNA methylation in the SLC6A4 gene and externalizing behavior in children of alcoholics (COA), and a matched sample of control children. Methods We examined children of alcoholics (N = 50) and age matched control children (N = 50) for exposure to early adversity (both prenatal and postnatal), assessed their salivary cortisol reactivity and evaluated their levels of emotional and behavioral difficulty in terms of externalizing and internalizing behavior. Site-specific DNA methylation at a previously characterized SLC6A4 region was determined in salivary DNA using pyrosequencing. The 5HTTLPR region of the SLC6A4 gene was also genotyped. Results COA had significantly higher experience of early adversity than control children. Cortisol reactivity was reduced in COA, and negatively correlated with early adversity. Both early adversity and cortisol reactivity correlated with externalizing behavior. SLC6A4 methylation was higher in COA, and correlated with early adversity. SLC6A4 genotype did not show association with any of the variables. Conclusion Our study provides further evidence that early adversity is associated with blunted cortisol reactivity, increased site-specific CpG DNA methylation at the SLC6A4 gene, and high externalizing behavior.