Unlike state-dependent biomarkers, markers of environmentally induced susceptibility are temporally stable traits that identify those who have become vulnerable to disorder as a consequence of environmental exposure (W. G. Iacono, 1985). Acquired characteristics, such as those secondary to perinatal complications or substance abuse, or those arising subsequent to trauma, fall into this category. Investigations of posttraumatic stress disorder (PTSD) have shown that traumatic exposure may generate such susceptibility markers. Comparing monozygotic twins discordant for combat exposure, Orr et al. (2003) found that elevated heart rate response to startling sounds was evident only in the exposed twins, suggesting that the cardiac response represents an acquired marker of PTSD rather than a sign of pre-existing genetic vulnerability. In a MEG study, combat veterans with PTSD and resilient combat veterans exposed to trauma without developing PTSD showed distinctly different patterns of neural network activity that were interpreted as accounting for differences in how trauma was encoded in the brain (James et al., 2013). Such environmentally mediated heart rate and MEG responses have many of the qualities of an endophenotype, but because they are
