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194 Biobehavioral Resilience to Stress

mice exhibit slightly prolonged recovery from CRF effects on startle and exag-

gerated effects of CRF on PPI (Risbrough, Hauger, Coste, Stenzel, Geyer, 2005);
this supports the hypothesis that CRF-R2 receptors inhibit CRF-R1 eff ects on
startle behavior.
It has been suggested that CRF-R2 receptor functions may be impor-
tant for stress recovery or “stress coping” and “resilience” (Coste, Heard,
Phillips & Stenzel-Poore, 2006; Coste, Murray & Stenzel-Poore, 2001; Reul
& Holsboer, 2002; Valdez, Sabino & Koob, 2004). CRF receptor genes have

been identified as good candidates for future genetic association studies
of anxiety phenotypes and startle phenotypes. To date, few association

studies have reported finding CRF system gene abnormalities in patients
with anxiety disorders. However, one interesting observation is that
polymorphism in the CRF gene is associated with behavioral inhibition,
which is a risk factor for the development of clinical anxiety (Smoller et al.,
2003, 2005). This area of research is new, but promising. Next, we consider

novel approaches to the identification of putative genetic links between

biological systems and PTSD.

Genomic Approaches to the Study of PTSD and Resilience

Contemporary large-scale DNA sequencing and polymorphism discovery
initiatives such as the Human Genome Project (HGP; www.genome.gov), the
ENCODE project (www.genome.gov), and the IHP (www.genome.gov and
www.hapmap.org) provide researchers with access to a wealth of informa-
tion and resources useful for the identifi cation of genes that are involved in
traits and diseases of all sorts. These resources can also be useful to the study

of PTSD and resilience, provided that researchers recognize specifi c caveats,
cautions, and guidelines.

Genome-Wide Human Association Studies
In the absence of prior knowledge concerning specific genes or polymorphic

DNA markers, one can “search” the genome for functionally relevant varia-
tions. Although family-based genome-wide linkage analyses have long been
used to support human gene discovery initiatives, the idea of sequentially
testing individual polymorphic sites directly for their possible association
with a particular trait was only recently proposed as a viable alternative to

studies based on prior knowledge of specific genes or polymorphic markers.*

* Lander and Schork (1994) provide a useful description of human gene discovery strate-
gies. See Risch and Merikangas (1996) for a discussion of the feasibility and merits of
linkage-based versus association-based genome-wide approaches to gene discovery.

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