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Posttraumatic Stress Disorder 185

Step 2: Identify the candidate environmental pathogen. In the case of PTSD, the
proximal “pathogen” is defined as traumatic stress. There is robust evidence

suggesting that such traumatic stress is, in fact, causally related to PTSD. Th us,
when PTSD symptoms occur, they are reliably linked to trauma. Animal mod-
els provide additional evidence that behavioral changes subsequent to severe

stress are related to specific protein synthesis and neurotransmitter changes
that occur in the same brain circuits and neurotransmitters, which are known
to play a role in PTSD (Adamec, Blundell & Burton, 2005, 2006; Inda, gado-
Garcia & Carrion, 2005; Rattiner, Davis & Ressler, 2004; Weaver et. al., 2005).
Charney and his colleagues provide a comprehensive review of relevant stress
neuropeptides and neurocircuitry (Bonne, Grillon, Vythilingam, Neumeister
& Charney, 2004; Charney, 2004).

Step 3: Optimize environmental risk measurement. Reliable measurement of
environmental risk requires attention to a number of factors. Th ese include
the potential cumulative nature of environmental infl uences, age-specifi c

effects of environmental pathogens, and the scientific dangers of using ret-

rospective recall data (Moffitt et al., 2005). To date, instruments and meth-

ods that have been developed to assess trauma exposure rely upon subjective
recall of the trauma (Keane et al., 1989). Ideally, assessment should employ
some additional, objective evaluation to verify the occurrence of the event,
to understand its potential impact in the context of cumulative eff ect, and
to generate an informed estimate of its intensity or severity. In principle, it
should be possible to develop such an assessment in the context of military
combat. Data from World War II show that the number of acute psychiat-
ric (combat stress) casualties could be predicted by the intensity of fi ghting

(numbers of physical casualties), mediated by the nature of the fight and the
quality of the troops involved (Jones & Wessely, 2001). Although the precise
relationship between combat-related stress and PTSD is not yet fully under-
stood, it may be possible to develop an objective measure of environmen-
tal “pathogenesis” based on evidence that negative outcome and severity of
symptoms are generally related to the intensity of the precipitating traumatic
event(s) (Green et al., 1990; King et al., 2000; Stein et al., 2002; Wolfe et al.,
2000). To be fully informative, such a measure should also take into account
the potentially cumulative nature of combat experience and exposure. With
these goals in mind, objective assessment can be achieved by careful docu-
mentation of structured interviews with well-informed cohorts (e.g., fellow

soldiers, squad leaders). This approach could be used to support retrospec-
tive and prospective studies to elucidate the environmental pathogenesis of
PTSD and to identify specific conditions, behavior, or characteristics that

render individuals more or less resilient to the disorder.
Step 4: Identify candidate susceptibility genes. Certainly, it would be ideal
if a researcher were able to identify candidate genes that reliably moderate

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