Abstract
Background: Decreased basal cortisol levels have been reported in individuals with
posttraumatic stress disorder (PTSD). There is evidence for enhanced negative feedback
sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis in PTSD, which could
account for this, but other possible mechanisms have not been ruled out. We examined
the HPA axis employing a metyrapone-cortisol infusion protocol designed to study negative
feedback sensitivity.
Methods: Vietnam combat trauma-exposed subjects met DSM-IV criteria for PTSD. Exclusion
criteria included substance abuse and most medications. Endogenous feedback inhibition
was removed by blocking cortisol synthesis with oral metyrapone and reintroduced by
intravenous infusion of cortisol. In a placebo condition, subjects received oral placebo
and normal saline infusion. Serial blood samples drawn over 4 hours were assayed for
adrenocorticotrophic hormone (ACTH), cortisol, and 11-deoxycortisol. Selected samples
were assayed for cortisol binding globulin (CBG) and dehydroepiandrosterone (DHEA).
Results: Basal plasma cortisol was significantly decreased in PTSD subjects (n = 13) compared with control subjects (n = 16). No significant difference in the ACTH response to cortisol infusion following
metyrapone was observed; however 11-deoxycortisol was significantly decreased in PTSD
subjects. In addition, CBG was significantly increased in PTSD subjects, and DHEA
was significantly decreased in both PTSD and combat-exposed control subjects.
Conclusions: These observations suggest decreased adrenocortical responsiveness may
be an additional or alternative mechanism accounting for low cortisol in PTSD.
Keywords
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Article info
Publication history
Accepted:
March 22,
2001
Received in revised form:
March 19,
2001
Received:
September 29,
2000
Identification
Copyright
© 2001 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
