The application proposes a series of projects to extend our current understanding of psychoneuroendocrine abnormalities in PTSD. During the years of the funded project we demonstrated differences between Holocaust survivors with and without PTSD on several neuroendocrine measures. Some of these changes (i.e., low urinary cortisol levels) were similar, but others (i.e., low catecholamine activity) were different than previously observed in other trauma survivors with PTSD. Holocaust survivors afford a unique opportunity to examine enduring effects of catastrophic trauma on neuroendocrine systems in men, and women who are similar in the type, severity, and length of time since trauma, as well as other sociodemographic factors, but who are free of confounds such as comorbid substance abuse, chronic treatment seeking behavior and disability. To better understand the mechanisms underlying the low cortisol and low catecholamine activity that we have recently observed in Holocaust survivors, we will examine the hormonal responses to neuroendocrine challenges and basal plasma neurohormonal release over a 24-hr period in three groups; Holocaust survivors with PTSD; Holocaust survivors without PTSD : and age and demographically comparable individuals who did not experience the Holocaust. We will perform two neuroendocrine challenge tests. The low dose dexamethasone suppression test will be used to evaluate negative feedback inhibition of the hypothalamic-pituitary-adrenal (HPA). The metyrapone stimulation test will be used to assess suprapituitary activation of the HPA axis. In both tests, we will characterize lymphocyte glucocorticoid receptor number under basal conditions and in response to dexamethasone and metyrapone administration. We will also characterize tahe circadian rhythm of cortisol, adrenocorticotropin (ACTH), norepinephrine (NE), and MHPG. By comparing the three groups using these paradigms we will be able to differentiate biological abnormalities that are specifically associated with PTSD from those that may be present as a result of trauma exposure, and take a critical step towards elucidating a general pathophysiology for PTSD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH049555-05
Application #
2675060
Study Section
Violence and Traumatic Stress Review Committee (VTS)
Project Start
1992-06-01
Project End
2001-04-30
Budget Start
1998-05-13
Budget End
1999-04-30
Support Year
5
Fiscal Year
1998
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
Grossman, Robert; Yehuda, Rachel; Golier, Julia et al. (2006) Cognitive effects of intravenous hydrocortisone in subjects with PTSD and healthy control subjects. Ann N Y Acad Sci 1071:410-21
Yehuda, R (2005) Neuroendocrine aspects of PTSD. Handb Exp Pharmacol :371-403
Golier, Julia A; Yehuda, Rachel; De Santi, Susan et al. (2005) Absence of hippocampal volume differences in survivors of the Nazi Holocaust with and without posttraumatic stress disorder. Psychiatry Res 139:53-64
Yehuda, Rachel; Golier, Julia A; Yang, Ren-Kui et al. (2004) Enhanced sensitivity to glucocorticoids in peripheral mononuclear leukocytes in posttraumatic stress disorder. Biol Psychiatry 55:1110-6
Yehuda, Rachel; Golier, Julia A; Halligan, Sarah L et al. (2004) The ACTH response to dexamethasone in PTSD. Am J Psychiatry 161:1397-403
Yehuda, Rachel; Halligan, Sarah L; Golier, Julia A et al. (2004) Effects of trauma exposure on the cortisol response to dexamethasone administration in PTSD and major depressive disorder. Psychoneuroendocrinology 29:389-404
Yehuda, Rachel (2003) Hypothalamic-pituitary-adrenal alterations in PTSD: are they relevant to understanding cortisol alterations in cancer? Brain Behav Immun 17 Suppl 1:S73-83
Yehuda, Rachel; Yang, Ren-Kui; Guo, Song Ling et al. (2003) Relationship between dexamethasone-inhibited lysozyme activity in peripheral mononuclear leukocytes and the cortisol and glucocorticoid receptor response to dexamethasone. J Psychiatr Res 37:471-7
Grossman, Robert; Yehuda, Rachel; New, Antonia et al. (2003) Dexamethasone suppression test findings in subjects with personality disorders: associations with posttraumatic stress disorder and major depression. Am J Psychiatry 160:1291-8
Yehuda, Rachel; Halligan, Sarah L; Yang, Ren Kui et al. (2003) Relationship between 24-hour urinary-free cortisol excretion and salivary cortisol levels sampled from awakening to bedtime in healthy subjects. Life Sci 73:349-58

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