Genome-wide analysis of stress-exposure-associated and exposure-related individual differences associated amygdala gene expression in males and females.

Delineating the molecular basis of individual differences in the stress response is critical to understanding the pathophysiology and treatment of posttraumatic stress disorder (PTSD). In this study, 7 d after predator-scent-stress (PSS) exposure, male and female rats were classified into vulnerable (i.e., PTSD-like) and resilient (i.e.,minimally affected) phenotypes on the basis of their performance on a variety of behavioral measures. Genome-wide expression profiling in blood and two limbic brain regions (amygdala and hippocampus), followed by quantitative PCR validation, was performed in these two groups of animals, as well as in an unexposed control group. Differentially expressed genes were identified in blood and brain associated with PSS-exposure and with distinct behavioral profiles postexposure. There was a small but significant between-tissue overlap (421%) for the genes associated with exposure-related individual differences, indicating convergent gene expression in both sexes. To uncover convergent signaling pathways across tissue and sex, upstream activated/deactivated transcription factorswere first predicted for each tissue and then the respective pathways were identified. Glucocorticoid receptor (GR) signaling was the only convergent pathway associatedwith individual differences when using the most stringent statistical threshold.

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Daskalakis NP, Cohen H, Cai G, Buxbaum JD, Yehuda R