ABSTRACT
Introduction ........................................................................................................ 178 Historical Overview ........................................................................................... 180
Genetic Epidemiology................................................................................... 180 Gene Association Studies ............................................................................. 182 Gene Expression Pro ling ........................................................................... 183
Issues and Approaches to the Study of PTSD ................................................ 184 Model Systems and the Genetic Basis of PTSD ............................................. 188
e Startle Response ..................................................................................... 188 e Startle Response as a Tool for Translational Research ..................... 189 Startle Endophenotypes Speci c to the Genetic Basis of Human PTSD ............................................................................................ 189 Animal Models of Fear Learning .................................................................191 Combining Behavioral and Biological Markers of PTSD Pathology ........................................................................................ 192 Pharmacologic Manipulation of CRF Systems and Startle Response ..................................................................................... 193
Genomic Approaches to the Study of PTSD and Resilience ........................ 194 Genome-Wide Human Association Studies .............................................. 194 Bioinformatically Informed Candidate Gene Studies ............................. 197 Pharmacological Studies and the Exploitation of Genetic Network Information ................................................................ 198
Conclusions and Recommendations ............................................................... 200 Acknowledgments .............................................................................................. 201 References ............................................................................................................ 201
Civilian exposure to accidents, physical and sexual assaults, human-made and natural disasters, and other life-threatening and traumatic events is common. In societies where rates of exposure have been measured, the lifetime prevalence of experiencing such events is reported to be between 17% and 80% (Alonso et al., 2004; Creamer, Burgess & McFarlane, 2001; Frans, Rimmo, Aberg & Fredrikson, 2005; Kessler, Sonnega, Bromet, Hughes & Nelson, 1995; Norris et al., 2003; Perkonigg, Kessler, Storz & Wittchen, 2000). Individuals working in professions such as re ghting, law enforcement, or the military are potentially confronted with random, ubiquitous life-threatening events as a part of their jobs. Exposure to traumatic or life-threatening events is associated with a subsequent increase in psychiatric illness, including posttraumatic stress disorder (PTSD) (Green, Lindy, Grace & Leonard, 1992; Kang, Dalager, Mahan & Ishii, 2005; Kang, Natelson, Mahan, Lee & Murphy, 2003). Longitudinal data from the Vietnam Veteran Twin Registry demonstrate that this link persists over time (Roy-Byrne et al., 2004). Indeed a causal link between the experience of a traumatic event and the diagnosis of PTSD is codi ed as part of the diagnostic de nition (designated Category A1 criterion) in Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV; American Psychiatric Association, 1994).
