Animal Models of Anxiety Vulnerability - The Wistar Kyoto Rat

1.1 Anxiety Anxiety disorders are the most common psychiatric disorders with a worldwide lifetime prevalence of 16-29% (Kessler et al., 2005; Somers et al., 2006). People with anxiety disorders are likely to suffer from depression and drug (or alcohol) abuse in an effort to gain relief from their symptoms, therefore, eliciting secondary disorders (Kessler et al., 2005). Although each subtype (i.e. generalized anxiety disorder, obsessive-compulsive disorder (OCD), panic disorder, post traumatic stress disorder (PTSD) and social phobia) has unique features, the core symptom of all anxiety disorders is excessive avoidance. The etiology of anxiety disorders remains elusive (the presumed role of trauma in PTSD notwithstanding). What is abundantly clear is anxiety disorders arise as a complex interaction of genetic, epigenetic, sociocultural factors with life experiences; that is, anxiety disorders are best explained with diathesis models (Kendler et al., 2002; Mineka and Zinbarg, 2006; Zinbarg and Barlow, 1996). Among a variety of neurobiological and neurobehavioral factors representing a source of risk for anxiety disorders, inhibited temperament is consistently linked to anxiety disorders (Biederman et al., 1993; Fox et al., 2005a; Hirshfeld et al., 1992; Hirshfeld-Becker et al., 2007; Kagan et al., 1987; Rosenbaum et al., 1993; Smoller et al., 2003). Behavioral inhibition is characterized as extreme withdrawal in the face of social and nonsocial challenges (Fox et al., 2005b; Kagan et al., 1989; Rosenbaum et al., 1991). Those with inhibited temperament exhibit excessive physiological reactivity to environmental challenges (Kalin et al., 2000; Kalin and Shelton, 2003; Keltikangas-Jarvinen et al., 1999; Perez-Edgar et al., 2007; Schwartz et al., 2003; Smoller et al., 2005; Tyrka et al., 2006; Tyrka et al., 2008). Although there is support for temperament as a risk factor, the translation of risk to actualized disorder is unclear. Acquisition, expression and retention of avoidance may be the final common pathway to anxiety disorders. The particularly debilitating feature of avoidance is that, left untreated, avoidance increases over time and leads to a worsening of symptoms. Avoidance acquisition is more apparent in PTSD; the growth of avoidance traces the full expression of PTSD (Karamustafalioglu et al., 2006; Kashdan et al., 2006; North et al., 2004; O'donnell et al., 2006a). Given this prominent position, avoidance learning may represent an endophenotype for anxiety disorders (Gould and Gottesman, 2006).