Hydrocortisone responsiveness in Gulf War veterans with PTSD: Effects on ACTH, declarative memory hippocampal [18F]FDG uptake on PET

Rachel Yehuda; Julia A. Golier; Linda M. Bierer; Arthur Mikhno; Laura C. Pratchett; Charles L. Burton; Iouri Makotkine; D. P. Devanand; Gnanavalli Pradhaban; Philip D. Harvey; J. John Mann

doi:10.1016/j.pscychresns.2010.06.010

Hydrocortisone responsiveness in Gulf War veterans with PTSD: Effects on ACTH, declarative memory hippocampal [¹⁸F]FDG uptake on PET

Rachel Yehuda, Julia A. Golier, Linda M. Bierer, Arthur Mikhno, Laura C. Pratchett, Charles L. Burton, Iouri Makotkine, D. P. Devanand, Gnanavalli Pradhaban, Philip D. Harvey, J. John Mann

Research output: Contribution to journal › Article › peer-review

34 Scopus citations

Abstract

Neuroendocrine, cognitive and hippocampal alterations have been described in Gulf War (GW) veterans, but their inter-relationships and significance for posttraumatic stress disorder (PTSD) have not been described. Hydrocortisone (Hcort) was administered to GW veterans with (PTSD+ n=12) and without (PTSD+ n=8) chronic PTSD in a randomized, placebo-controlled, double-blind challenge. Changes in plasma ACTH, memory, and hippocampal [¹⁸F]FDG uptake on positron emission tomography were assessed. The low-dose dexamethasone suppression test was also administered. The PTSD+ group showed greater cortisol and ACTH suppression, reflecting greater peripheral glucocorticoid receptor (GR) responsiveness, and did not show an Hcort-induced decrement in delayed recall or retention. The groups had comparable relative regional hippocampal [¹⁸F]FDG uptake at baseline, but only the PTSD+ group had an Hcort-associated decrease in hippocampal [¹⁸F]FDG uptake. Asymmetry in hippocampal hemispheric volumes differed between PTSD+ and PTSD+ groups. This asymmetry was associated with cortisol, ACTH, retention and functional hippocampal asymmetry before, but not after, Hcort administration. Differences in brain metabolic responses between GW veterans with and without PTSD may reflect differences in peripheral and central GR responsiveness.

Original language	English
Pages (from-to)	117-127
Number of pages	11
Journal	Psychiatry Research - Neuroimaging
Volume	184
Issue number	2
DOIs	https://doi.org/10.1016/j.pscychresns.2010.06.010
State	Published - Nov 2010

Keywords

Cortisol
Episodic memory
Glucocorticoid receptors
Gulf War veterans
Hippocampus
PTSD
[F]FDG-PET

Access to Document

10.1016/j.pscychresns.2010.06.010

Cite this

Yehuda, R., Golier, J. A., Bierer, L. M., Mikhno, A., Pratchett, L. C., Burton, C. L., Makotkine, I., Devanand, D. P., Pradhaban, G., Harvey, P. D., & Mann, J. J. (2010). Hydrocortisone responsiveness in Gulf War veterans with PTSD: Effects on ACTH, declarative memory hippocampal [¹⁸F]FDG uptake on PET. Psychiatry Research - Neuroimaging, 184(2), 117-127. https://doi.org/10.1016/j.pscychresns.2010.06.010

@article{24e2ed8a36b04cd6ae27a3f37df12fbe,

title = "Hydrocortisone responsiveness in Gulf War veterans with PTSD: Effects on ACTH, declarative memory hippocampal [18F]FDG uptake on PET",

abstract = "Neuroendocrine, cognitive and hippocampal alterations have been described in Gulf War (GW) veterans, but their inter-relationships and significance for posttraumatic stress disorder (PTSD) have not been described. Hydrocortisone (Hcort) was administered to GW veterans with (PTSD+ n=12) and without (PTSD+ n=8) chronic PTSD in a randomized, placebo-controlled, double-blind challenge. Changes in plasma ACTH, memory, and hippocampal [18F]FDG uptake on positron emission tomography were assessed. The low-dose dexamethasone suppression test was also administered. The PTSD+ group showed greater cortisol and ACTH suppression, reflecting greater peripheral glucocorticoid receptor (GR) responsiveness, and did not show an Hcort-induced decrement in delayed recall or retention. The groups had comparable relative regional hippocampal [18F]FDG uptake at baseline, but only the PTSD+ group had an Hcort-associated decrease in hippocampal [18F]FDG uptake. Asymmetry in hippocampal hemispheric volumes differed between PTSD+ and PTSD+ groups. This asymmetry was associated with cortisol, ACTH, retention and functional hippocampal asymmetry before, but not after, Hcort administration. Differences in brain metabolic responses between GW veterans with and without PTSD may reflect differences in peripheral and central GR responsiveness.",

keywords = "Cortisol, Episodic memory, Glucocorticoid receptors, Gulf War veterans, Hippocampus, PTSD, [F]FDG-PET",

author = "Rachel Yehuda and Golier, {Julia A.} and Bierer, {Linda M.} and Arthur Mikhno and Pratchett, {Laura C.} and Burton, {Charles L.} and Iouri Makotkine and Devanand, {D. P.} and Gnanavalli Pradhaban and Harvey, {Philip D.} and Mann, {J. John}",

note = "Funding Information: This grant was primarily supported by a VA MERIT entitled “Glucocorticoid Responsivity in Gulf War Veterans.” In addition, partial support was obtained by a grant ( 5 MO1 RR00071 ) for the Mount Sinai General Clinical Research Center from the National Center for Research Resources, National Institutes of Health . The authors would like to acknowledge several colleagues for work on this project. First, thanks to Josef Machac, M.D. and Ash Rafique, B.S. at the Mount Sinai Hospital Clinical Neuroimaging Laboratory, to Janelle Wohltmann, B.A., Research Coordinator, to Lisa Tischler, Ph.D., Sharon Y. Jedel, Psy.D., and Ellen Labinsky, Ph.D. for psychological assessments of the subjects, to Ken Belzer, Ph.D., for statistical consultation, and most of all, the Gulf War Veterans who participated in this research.",

year = "2010",

month = nov,

doi = "10.1016/j.pscychresns.2010.06.010",

language = "English",

volume = "184",

pages = "117--127",

journal = "Psychiatry Research - Neuroimaging",

issn = "0925-4927",

publisher = "Elsevier Ireland Ltd",

number = "2",

}

Yehuda, R , Golier, JA, Bierer, LM, Mikhno, A, Pratchett, LC, Burton, CL, Makotkine, I, Devanand, DP, Pradhaban, G, Harvey, PD & Mann, JJ 2010, 'Hydrocortisone responsiveness in Gulf War veterans with PTSD: Effects on ACTH, declarative memory hippocampal [¹⁸F]FDG uptake on PET', Psychiatry Research - Neuroimaging, vol. 184, no. 2, pp. 117-127. https://doi.org/10.1016/j.pscychresns.2010.06.010

TY - JOUR

T1 - Hydrocortisone responsiveness in Gulf War veterans with PTSD

T2 - Effects on ACTH, declarative memory hippocampal [18F]FDG uptake on PET

AU - Yehuda, Rachel

AU - Golier, Julia A.

AU - Bierer, Linda M.

AU - Mikhno, Arthur

AU - Pratchett, Laura C.

AU - Burton, Charles L.

AU - Makotkine, Iouri

AU - Devanand, D. P.

AU - Pradhaban, Gnanavalli

AU - Harvey, Philip D.

AU - Mann, J. John

N1 - Funding Information: This grant was primarily supported by a VA MERIT entitled “Glucocorticoid Responsivity in Gulf War Veterans.” In addition, partial support was obtained by a grant ( 5 MO1 RR00071 ) for the Mount Sinai General Clinical Research Center from the National Center for Research Resources, National Institutes of Health . The authors would like to acknowledge several colleagues for work on this project. First, thanks to Josef Machac, M.D. and Ash Rafique, B.S. at the Mount Sinai Hospital Clinical Neuroimaging Laboratory, to Janelle Wohltmann, B.A., Research Coordinator, to Lisa Tischler, Ph.D., Sharon Y. Jedel, Psy.D., and Ellen Labinsky, Ph.D. for psychological assessments of the subjects, to Ken Belzer, Ph.D., for statistical consultation, and most of all, the Gulf War Veterans who participated in this research.

PY - 2010/11

Y1 - 2010/11

N2 - Neuroendocrine, cognitive and hippocampal alterations have been described in Gulf War (GW) veterans, but their inter-relationships and significance for posttraumatic stress disorder (PTSD) have not been described. Hydrocortisone (Hcort) was administered to GW veterans with (PTSD+ n=12) and without (PTSD+ n=8) chronic PTSD in a randomized, placebo-controlled, double-blind challenge. Changes in plasma ACTH, memory, and hippocampal [18F]FDG uptake on positron emission tomography were assessed. The low-dose dexamethasone suppression test was also administered. The PTSD+ group showed greater cortisol and ACTH suppression, reflecting greater peripheral glucocorticoid receptor (GR) responsiveness, and did not show an Hcort-induced decrement in delayed recall or retention. The groups had comparable relative regional hippocampal [18F]FDG uptake at baseline, but only the PTSD+ group had an Hcort-associated decrease in hippocampal [18F]FDG uptake. Asymmetry in hippocampal hemispheric volumes differed between PTSD+ and PTSD+ groups. This asymmetry was associated with cortisol, ACTH, retention and functional hippocampal asymmetry before, but not after, Hcort administration. Differences in brain metabolic responses between GW veterans with and without PTSD may reflect differences in peripheral and central GR responsiveness.

AB - Neuroendocrine, cognitive and hippocampal alterations have been described in Gulf War (GW) veterans, but their inter-relationships and significance for posttraumatic stress disorder (PTSD) have not been described. Hydrocortisone (Hcort) was administered to GW veterans with (PTSD+ n=12) and without (PTSD+ n=8) chronic PTSD in a randomized, placebo-controlled, double-blind challenge. Changes in plasma ACTH, memory, and hippocampal [18F]FDG uptake on positron emission tomography were assessed. The low-dose dexamethasone suppression test was also administered. The PTSD+ group showed greater cortisol and ACTH suppression, reflecting greater peripheral glucocorticoid receptor (GR) responsiveness, and did not show an Hcort-induced decrement in delayed recall or retention. The groups had comparable relative regional hippocampal [18F]FDG uptake at baseline, but only the PTSD+ group had an Hcort-associated decrease in hippocampal [18F]FDG uptake. Asymmetry in hippocampal hemispheric volumes differed between PTSD+ and PTSD+ groups. This asymmetry was associated with cortisol, ACTH, retention and functional hippocampal asymmetry before, but not after, Hcort administration. Differences in brain metabolic responses between GW veterans with and without PTSD may reflect differences in peripheral and central GR responsiveness.

KW - Cortisol

KW - Episodic memory

KW - Glucocorticoid receptors

KW - Gulf War veterans

KW - Hippocampus

KW - PTSD

KW - [F]FDG-PET

UR - http://www.scopus.com/inward/record.url?scp=78650204453&partnerID=8YFLogxK

U2 - 10.1016/j.pscychresns.2010.06.010

DO - 10.1016/j.pscychresns.2010.06.010

M3 - Article

C2 - 20934312

AN - SCOPUS:78650204453

SN - 0925-4927

VL - 184

SP - 117

EP - 127

JO - Psychiatry Research - Neuroimaging

JF - Psychiatry Research - Neuroimaging

IS - 2