Methylation of OXTR is associated with participation in SAAF through its effect on substance use initiation. This both illustrates an avenue by which family-based prevention programs may become biologically embedded, and highlights methylation of OXTR as a potentially useful biomarker of the impact of such programs. Methylation of the oxytocin receptor (OXTR), a gene known to be involved in social skills and cognition relating to empathy, trust, and optimism (MacDonald & MacDonald, 2010), was a natural choice as a biomarker of SAAF induced change. In keeping with prior research on genetic susceptibility for behavioral effects of SAAF, the current study investigated whether carriers of the “s” allele of the 5-HTTLPR would also show a different pattern of epigenetic change at OXTR in response to SAAF. Given the strong connection between serotonergic and oxytonergic systems (Galfi, et al., 2005), we posited that methylation of OXTR would be greater for those initiating early substance use to the extent they also carried the “s” allele, but would be less for those protected against early substance use initiation by participation in SAAF, or who