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184 Biobehavioral Resilience to Stress

PBMC gene expression for transcription activators among PTSD-vulnerable
individuals, and also found that the genes, which differentiated PTSD sub-

jects from non-PTSD subjects included stress-related response genes. More-
over, these same expression patterns correlated with the severity of each of
three PTSD symptom clusters that were assessed at 4 months postexposure
(Segman et al., 2005).

Although findings such as those reported by Segman et al. (2005) are
of great interest and potentially informative, it is important to note that
there remain unresolved issues and questions surrounding the use of gene
expression microarrays and blood cells to identify genes that infl uence com-
plex traits such as PTSD risk or resilience. For example, to the extent that

a specific disorder or disease has its source in lesions that aff ect the brain,

the tissue specificity of gene expression raises the question of whether gene
variations derived from a peripheral blood source are biologically relevant.

Issues and Approaches to the Study of PTSD

Several authors have addressed challenges inherent to the design of studies
that are intended to identify and characterize the combined eff ects of genes
and environmental factors on phenotypic expression (Eaves & Erkanli, 2003;
Grigorenko, 2005; Kelada, Eaton, Wang, Rothman & Khoury, 2003; Kramer

et al., 2005; Rutter, 2005). Moffitt, Caspi, and Rutter (2005) offer an espe-
cially useful discussion of the feasibility of such studies with respect to neu-

ropsychiatric phenotypes. Moffitt et al. (2005) discuss seven specifi c strategic
“steps” that should be taken in the conduct of such research. In this section,
we apply this same series of strategic recommendations as an approach to
address the challenges and limitations associated with the scientifi c eff ort to
identify genetic factors that contribute to PTSD.

Step 1: Consult quantitative behavioral-genetic models. Th is first step calls
upon prospective researchers to first consider existing evidence that a behav-

ioral trait may have any genetic basis at all (Moffitt et al., 2005). In the case of

PTSD, twin studies provide initial evidence that risk and resilience to PTSD
are heritable tendencies. Additional evidence can be found in retrospec-

tive studies of probands from families whose members suffer from PTSD or
other mental illnesses such as depression, anxiety disorders, and even psy-
chosis (Breslau, Davis, Andreski & Peterson, 1991; Breslau, Davis, Peterson &
Schultz, 1997; Bromet, Sonnega & Kessler, 1998; Cottler, Nishith & Compton,
III, 2001; Reich, Lyons & Cai, 1996; Sack, Clarke & Seeley, 1995; Skre, Onstad,
Torgersen, Lygren & Kringlen, 1993). However, no such effect has been found

for individuals from families with alcohol or illicit substance abuse (Breslau
et al., 1997; Cottler et al., 2001).

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