First, extant studies in the field have not incorporated data about the environmental exposures that are thought to initiate epigenetic change—in a recent review of the literature,[27] only 3 of 21 studies sought to assess the differential influence of epigenetic modifications on psychiatric outcomes among individuals with a history of a common environmental stressor.[23,28,29] Despite ample population data suggesting that psychopathology is environmentally determined,[30] our studies are not equipped to address dominant hypotheses about the mediating role of epigenetic changes in these relationships because they have not assessed epigenetic modification in relation to environmental exposures known to predict these outcomes. Moreover, it may not be sufficient to measure such exposures at one point in time. For example, it is plausible that cumulative exposure, the most extreme level of exposure at any time point, or exposure level during a particularly sensitive point in the life course may be more important in the etiology of outcomes of interest, and therefore, investigators should take care to operationalize exposures of interest in several different ways.
