Low early morning plasma cortisol in posttraumatic stress disorder is associated with co-morbid depression but not with enhanced glucocorticoid feedback inhibition

Vythilingam, M.; Gill, J.M.; Luckenbaugh, D.A.; Gold, P.W.; Collin, C.; Bonne, O.; Plumb, K.; Polignano, E.; West, K.; Charney, D.

doi:10.1016/j.psyneuen.2009.08.006

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Volume 35, Issue 3 , Pages 442-450, April 2010

Low early morning plasma cortisol in posttraumatic stress disorder is associated with co-morbid depression but not with enhanced glucocorticoid feedback inhibition

M. Vythilingam
- Mood and Anxiety Disorders Program, National Institute of Mental Health, Bethesda, MD 20892, USA
- Corresponding author at: Psychological Health Strategic Operations, Force Health Protection & Readiness, Office of the Assistant Secretary of Defense (Health Affairs), Skyline 4, Suite 403, 5113 Leesburg Pike, Falls Church, VA 22041. Tel.: +1 301 594 1798; fax: +1 301 594 9959.
J.M. Gill
- National Institutes of Nursing Research, Bethesda, MD 20892, USA
D.A. Luckenbaugh
- Mood and Anxiety Disorders Program, National Institute of Mental Health, Bethesda, MD 20892, USA
P.W. Gold
- Mood and Anxiety Disorders Program, National Institute of Mental Health, Bethesda, MD 20892, USA
C. Collin
- Mood and Anxiety Disorders Program, National Institute of Mental Health, Bethesda, MD 20892, USA
O. Bonne
- Department of Psychiatry, Hadassah Hebrew University Medical Center, Jerusalem, Israel
K. Plumb
- Mood and Anxiety Disorders Program, National Institute of Mental Health, Bethesda, MD 20892, USA
E. Polignano
- Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA
K. West
- Mood and Anxiety Disorders Program, National Institute of Mental Health, Bethesda, MD 20892, USA
D. Charney
- Mount Sinai School of Medicine, New York, NY, USA

Received 6 January 2009; received in revised form 29 June 2009; accepted 13 August 2009.

Summary

Background

Co-morbid major depressive disorder (MDD) in individuals with posttraumatic stress disorder (PTSD) confers a more severe clinical course and is associated with distinct biologic abnormalities. Although dysregulation in the hypothalamic pituitary adrenal (HPA) axis has been well established in PTSD, the impact of commonly co-occuring MDD has received scant attention.

Methods

Overnight (7p.m. to 7a.m.) plasma cortisol, adrenocorticotropic hormone (ACTH), dehydroepiandrosterone sulphate (DHEA-S) were measured at 30min intervals in 9 participants with PTSD with MDD (PTSD+MDD), 9 with PTSD without MDD (PTSD−MDD) and 16 non-traumatized healthy controls. A low-dose dexamethasone suppression test was administered to evaluate feedback sensitivity to glucocorticoids. Linear mixed models with body mass index (BMI) and age as covariates and Bonferroni corrected post hoc tests assessed group differences.

Results

Compared to healthy controls, subjects with PTSD+MDD, but not those subjects with PTSD−MDD, exhibited lower basal plasma cortisol levels between 1:30a.m. and 3:30a.m. and at 4:30a.m. and 6:30a.m. (effect size d=0.75). Despite similar plasma ACTH levels between the three groups, the ACTH/cortisol ratio was higher in PTSD+MDD patients compared to controls. We obtained similar results when the patient and control groups were re-studied 1 week later, and when men and current smokers were excluded. Basal plasma DHEA-S levels, and cortisol and ACTH response to a low-dose dexamethasone suppression test were similar in all three groups.

Conclusions

Lower early morning plasma cortisol levels and a high ACTH/cortisol ratio in subjects with PTSD and co-morbid MDD may not be due to enhanced peripheral sensitivity to glucocorticoids. A central abnormality in glucocorticoid regulation could explain HPA axis dysfunction in this subgroup.

Keywords: PTSD, Depression, Cortisol, DHEA-S, ACTH