The relevance of differential response to trauma in an animal model of posttraumatic stress disorder

Background: Posttraumatic stress disorder affects 20%-30% of those exposed. Clinical studies employ stringent inclusion-exclusion criteria, yet animal studies include the entire exposed population as the study population. We examined the effect of grouping prestressed rats according to magnitude of response on the statistical analysis of results. Method: Response magnitude to predator exposure was assessed and used to group the animals into "diagnostic" groups. Two extremes were studied (clearly "maladapted" and clearly "well adapted" rats) using arbitrarily selected cutoff behavioral criteria (CBC). The data for the middle group were discarded for reasons of clarity. Hypothalamic-pituitary-adrenal axis and heart-rate variability were analyzed for the entire exposed population and then according to the CBC. Results: A single 10-min exposure to a predator caused fear-related behaviors in only 25.3% of exposed rats. Compared with control subjects and well-adapted exposed rats, maladapted rats exhibited significantly higher plasma corticosterone and corticotropin concentrations, increased sympathetic activity, diminished vagal tone, and increased sympathovagal balance. These differences surfaced only when data were analyzed according to CBC. Conclusions: Animals respond to stress heterogeneously, resembling humans. Overlooking this heterogeneity may obscure the results of data analysis. Animals can be divided into distinct groups according to magnitude of response and be studied accordingly.