Enhanced sensitivity to glucocorticoids in peripheral mononuclear leukocytes in posttraumatic stress disorder

Rachel Yehuda, Julia A. Golier, Ren Kui Yang, Lisa Tischler

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169 Scopus citations

Abstract

Background The aim of this study was to determine whether there is increased responsiveness to corticosteroids in posttraumatic stress disorder (PTSD) by examining the differential effects of dexamethasone (DEX) on the inhibition of lysozyme activity. Methods 60 mL of blood was withdrawn at 8:00 am, and mononuclear leukocytes were isolated from the blood of 26 men with, and 18 men without, PTSD. An aliquot of live cells was incubated with a series of concentrations of DEX to determine the rate of inhibition of lysozyme activity; a portion of cells was frozen for the determination of glucocorticoid receptors (GR). Results Subjects with PTSD showed evidence of a greater sensitivity to glucocorticoids as reflected by a significantly lower mean concentration (nmol/L) of dexamethasone at which 50% of lysozyme activity is inhibited (IC50-DEX) (PTSD+ = 4.9 ± .53; PTSD- group = 7.2 ± .64). The lysozyme IC50-DEX was significantly correlated with age at exposure to the first traumatic event in subjects with PTSD (r = .44, n = 26, p = .025). The number of cytosolic glucocorticoid receptors was also correlated with age at exposure to the focal traumatic event (r = -.44, n = 25, p = .03) in PTSD. Conclusions This is the first in vitro demonstration of an alteration in target tissue sensitivity to glucocorticoids in PTSD. The lower lysozyme IC 50-DEX might be related to the risk factor of prior exposure to trauma.

Original languageEnglish
Pages (from-to)1110-1116
Number of pages7
JournalBiological Psychiatry
Volume55
Issue number11
DOIs
StatePublished - 1 Jun 2004
Externally publishedYes

Keywords

  • PTSD
  • dexamethasone
  • glucocorticoid receptors
  • lymphocytes (mononuclear leukocytes)

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