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Posttraumatic Stress Disorder 191

(Swerdlow et al., 2005). More consistent and interpretable results are likely
when startle changes are elicited by an experimental stimulus (e.g., prepulse
or stressor), which permits baseline normalization (percentage change) and
baseline matching (Baas, Nugent, Lissek, Pine & Grillon, 2004; Cornwell,
Johnson, Berardi & Grillon, 2006; de Jongh, Groenink, van der Gugten &
Olivier, 2003; Swerdlow et al., 2005; Walker & Davis, 2002b).
The startle response can also be used to measure fear learning or stress

recovery, which have been found to be altered in individuals with PTSD and
other anxiety disorders (Lissek et al., 2005; Orr et al., 2000; Rothbaum &
Davis, 2003). In this way, the startle response may be used as a more spe-

cific means to identify genes or systems that mediate PTSD. For example,
enhanced fear conditioning and reduced fear extinction can be measured
by acquisition and extinction of FPS (Jovanovic et al., 2005; Orr et al., 2000;
Walker & Davis, 2002a), stress-induced sensitization of startle (Grillon &
Morgan, 1999; Yilmazer-Hanke, Faber-Zuschratter, Linke & Schwegler,
2002; Yilmazer-Hanke, Roskoden, Zilles & Schwegler, 2003; Yilmazer-
Hanke, Wigger, Linke, Landgraf & Schwegler, 2004), or delayed behavioral
recovery from stress (Adamec, 1997; Shalev et al., 2000). Divergent endophe-
notypes of highly heritable traits (e.g., FPS; Falls, Carlson, Turner & Willott,
1997; McCaughran, Bell & Hitzemann, 2000; Risbrough, Brodkin & Geyer,
2003; Risbrough & Geyer, 2005) may provide a basis for the modeling of
genetic mechanisms. Cohen and Zohar (2004) observed that only a small
percentage of rats demonstrate exaggerated and prolonged stress responses

after “trauma” (in this case, predator odor). Selective breeding of trauma-
responsive and trauma-nonresponsive rats could support the development of
an animal model of genetic vulnerability to PTSD.

Animal Models of Fear Learning

Animal models of fear responding (e.g., conditioned fear) have revealed a
wealth of new candidate genes and systems that may be important for acquir-
ing, maintaining, and inhibiting conditioned fear responses. For example,
researchers at the Eric Kandel Research Laboratory have recently discovered
two genes, gastrin-related peptide (GRP) and oncoprotein 18/stathmin, that
modulate performance in learned fear (amygdala dependent) tasks without

affecting spatial working memory (hippocampus dependent) (Shumyatsky

et al., 2002, 2005). The stathmin gene appears to be required for normal fear
learning, while the GRP appears to inhibit anxiety and learned fear respon-
siveness. The apparent specificity of these genes for fear-related memory

functions (versus cognition in general) is very exciting, because it suggests

that these genes might also be specifically involved with anxiety disorders
such as PTSD, or with putative alterations in fear learning and extinction.
The impact of functional mutations to these genes on anxiety in human

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