Neuroendocrine studies examining hypothalamic-pituitary adrenal (HPA) activity under both baseline conditions and in response to neuroendocrine challenges have suggested a dysregulation of this axis in war veterans with chronic post-traumatic stress disorder (PTSD). To date, there is much debate regarding whether these alterations suggest a specific pathophysiology of PTSD, or rather, reflect a comorbid major depressive disorder (MDD). Our previous work has shown that HPA axis abnormalities are present in PTSD, and that these abnormalities appear to be distinct from those observed in MDD. For example, in two separate studies from our laboratory, a lower mean 24-hour urinary cortisol excretion was observed in combat veterans with PTSD compared to patients with MDD and normal males. Two studies are proposed to further characterize HPA axis abnormalities in PTSD. The first study will examine basal circadian secretion of cortisol and corresponding changes in lymphocyte glucocorticoid receptors (GR) in combat veterans with PTSD compared to patients with MDD and both combat and nonveteran nonpsychiatric, healthy males. Based on our pilot data, it is hypothesized that combat veterans with PTSD will show an increased number of lymphocyte GR compared to all other groups, which is consistent with low ambient levels of circulating glucocorticoids. In the second study, the possibility of an enhanced negative feedback sensitivity of the HPA axis in PTSD will then be investigated using a low-dose dexamethasone (DEX) challenge paradigm. For this study, cortisol and corresponding changes in lymphocyte CR in response to 0.50 mg and 0.25 mg of DEX will be measured. Based on pilot data, it is hypothesized that patients with PTSD will show an enhanced suppression of cortisol to both doses of DEX compared to both patients with MDD and nonpsychiatric controls. Furthermore, a significant relationship between lymphocyte GR number and the cortisol response to DEX is hypothesized (i.e., patients with high GR numbers will show low cortisol secretion following low dose DEX).

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Small Research Grants (R03)
Project #
5R03MH049536-02
Application #
2248944
Study Section
Mental Health Small Grant Review Committee (MSM)
Project Start
1991-09-30
Project End
1994-08-31
Budget Start
1992-09-15
Budget End
1994-08-31
Support Year
2
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Psychiatry
Type
Schools of Medicine
DUNS #
114400633
City
New York
State
NY
Country
United States
Zip Code
10029
Golier, J A; Yehuda, R; Schmeidler, J et al. (2001) Variability and severity of depression and anxiety in post traumatic stress disorder and major depressive disorder. Depress Anxiety 13:97-100
Yehuda, R (1998) Psychoneuroendocrinology of post-traumatic stress disorder. Psychiatr Clin North Am 21:359-79
Yehuda, R; Resnick, H S; Schmeidler, J et al. (1998) Predictors of cortisol and 3-methoxy-4-hydroxyphenylglycol responses in the acute aftermath of rape. Biol Psychiatry 43:855-9
Yehuda, R; Schmeidler, J; Siever, L J et al. (1997) Individual differences in posttraumatic stress disorder symptom profiles in Holocaust survivors in concentration camps or in hiding. J Trauma Stress 10:453-63
Golier, J; Yehuda, R; Cornblatt, B et al. (1997) Sustained attention in combat-related posttraumatic stress disorder. Integr Physiol Behav Sci 32:52-61
Yehuda, R; Levengood, R A; Schmeidler, J et al. (1996) Increased pituitary activation following metyrapone administration in post-traumatic stress disorder. Psychoneuroendocrinology 21:1-16
Yehuda, R; Elkin, A; Binder-Brynes, K et al. (1996) Dissociation in aging Holocaust survivors. Am J Psychiatry 153:935-40
Yehuda, R; Teicher, M H; Trestman, R L et al. (1996) Cortisol regulation in posttraumatic stress disorder and major depression: a chronobiological analysis. Biol Psychiatry 40:79-88
Yehuda, R; Boisoneau, D; Lowy, M T et al. (1995) Dose-response changes in plasma cortisol and lymphocyte glucocorticoid receptors following dexamethasone administration in combat veterans with and without posttraumatic stress disorder. Arch Gen Psychiatry 52:583-93
Yehuda, R; Kahana, B; Binder-Brynes, K et al. (1995) Low urinary cortisol excretion in Holocaust survivors with posttraumatic stress disorder. Am J Psychiatry 152:982-6

Showing the most recent 10 out of 23 publications