Second, unmeasured confounders are pervasive in this literature and challenge the validity of existing studies in the area. Confounders are third variables that predict both exposure and outcome, but that do not mediate the relationship between them.[31,32] In studies about the relation between epigenetic modification and psychopathology it is plausible that environmental factors that both cause epigenetic change and independently cause psychiatric outcomes may confound the relationship in question. For example, studies in animal models have demonstrated that maternal social support during infancy, but also social support from others, including fathers, siblings, and extended family members throughout youth produces epigenetic changes that influence social behavior in adult life.[33] Extending to observational studies about psychopathology in humans where experimentation is not possible, it is necessary, then, to differentiate the social influences of peer support in later life from the influences of epigenetic modifications resulting from maternal care or child maltreatment on outcomes of interest.
