1. I think that the mechanism that leads to increased cortisol response in pups reared in a low “maternal licking and grooming” environment is highly relevant to humans. In humans the most analogous maternal behavior is breastfeeding of newborns in the first year of life. The biological connection made between mothers and their newborns in the first year of life is analogous to the biological connection engendered by “maternal licking and grooming” in the first week of the pup’s life. In both cases the connection is deeper than the operational outcome (i.e., getting fed, or cleaned). Both behaviors require touching that triggers cellular sensing mechanisms linked to gene expression pathways, and nurturing communication that affects neuroendocrine pathways.
2. I think that the Gruenewald findings in humans are consistent with extrapolation of the Weaver findings in rats. The findings of Weaver et al provide a mechanistic understanding of how the absence or presence of one maternal behavior (licking and grooming) affects epigenetic regulation of a single gene at a single developmental window in the pup. The alteration found in the single gene for the glucocorticoid receptor in the pup then affects its cortisol reactivity into adulthood. Similarly, the findings of Gruenewald can be explained as the altered expression of many genes that are triggered by signals specific to low or high SES conditions at different times in the life course. Based on the findings of Weaver genes responsible for the outcomes found in Gruenewald likely have different windows of susceptibility to epigenetic regulation, this regulation could be reversible, and the change in expression of one gene could lead to changes in other genes explaining the complex trends found.
3. I think that GxE interactions play a significant role in health disparities because it is the interplay between a person’s individual genetics and personal environments that lead to disease. In particular, different biological, social, and physical components of GxE interactions can drive disparities. For example, with respect to racial/ethnic disparities the individual’s admixture (biological) and their relative rank in society (social) can affect health outcomes. With respect to SES, individuals with genetic predispositions to particular diseases (biological) can succumb to these predispositions in low SES environments if they fail to have access to screening/treatment (social), and/or are exposed to triggering toxins (physical). With respect to geographic dimensions it is important to remember that because of human evolution and migration genetic variations (biological) that predispose humans to disease are geographically clustered. These are passed on, or not, through cultural practices (social) that are specific to particular geographic locations. Moreover, different geographic locations have varying levels of toxins (physical) that can trigger susceptibility. In all cases, however, the susceptibility of individuals to disease because of their own GxE interactions can be reduced or eliminated by improving the social/physical environment in which they live. This is the best target for prevention of health disparities.