Level of Expression and Functional Properties of Lymphocyte Corticosteroid Receptors as Biological Correlates of PTSD, Trauma-Exposure, or Resilience to PTSD

Abstract

This chapter summarizes current research on glucocorticoid receptor (GR) functional alterations associated with trauma exposure, posttraumatic stress disorder (PTSD) psychopathology, and resilience and vulnerability to PTSD. Special attention is paid to hormone-binding activity of the receptor, the level of its expression, its ratio to mineralocorticoid receptor (MR), and the interactions of corticosteroid receptors with heat shock protein chaperones, Hsp90 and Hsp70. Determinations of GR number (Bmax) and assessments of lymphocyte sensitivity to glucocorticoids in trauma-exposed individuals with and without PTSD have yielded rather inconsistent results. The contribution of most other factors determining tissue responsiveness to glucocorticoid hormones to PTSD pathophysiology is currently under investigation. Thus, increased GR protein level in peripheral lymphocytes from current and lifetime PTSD patients in comparison to trauma-exposed non-PTSD individuals (trauma controls) appeared to be a possible correlate of vulnerability to PTSD. Besides, PTSD patients displayed the lowest and trauma controls the highest fractional occupancy of the GR, suggesting that the receptor redox status may be a factor contributing to vulnerability/resilience to PTSD. Estimates of the GR hormone-binding potency (Bmax/KD ratio) and of strength of correlation between Bmax and KD pointed to deterioration of glucocorticoid signaling in the lymphocytes as a characteristic of PTSD patients. Lymphocyte MR protein level, MR/GR ratio, and Hsp90 and Hsp70 levels were found to be unaffected by traumatic events and past or current PTSD symptoms. However, the association of GR and Hsp90 expression levels appeared as a candidate marker of trauma exposure, while that of MR and Hsp70 levels of vulnerability to PTSD.