Enhanced sensitivity to glucocorticoids in peripheral mononuclear leukocytes in posttraumatic stress disorder.
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60 mL of blood was withdrawn at 8:00 am, and mononuclear leukocytes were isolated from the blood of 26 men with, and 18 men without, PTSD.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 (IC(50-DEX)) (PTSD+ = 4.9 +/-.53; PTSD- group = 7.2 +/-.64). The lysozyme IC(50-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.
Yehuda
Rachel
R
Department of Psychiatry, Mount Sinai School of Medicine, and Bronx Veterans Affairs Medical Center, New York, New York 10468, USA.
Golier
Julia A
JA
Yang
Ren-Kui
RK
Tischler
Lisa
L
D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D002452:Cell Count / Q000379:methods; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D020128:Inhibitory Concentration 50; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009113:Muramidase / Q000378:metabolism; D011869:Radioligand Assay / Q000379:methods; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D013313:Stress Disorders, Post-Traumatic / Q000097:blood / Q000473:pathology*
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D009113:Muramidase; D006854:Hydrocortisone