Basal and suppressed salivary cortisol in female Vietnam nurse veterans with and without PTSD

Abstract

It has been suggested that discrepant findings regarding low basal cortisol levels and enhanced suppression of cortisol in response to dexamethasone (DEX) administration in post-traumatic stress disorder (PTSD) may reflect individual differences in gender, trauma type, stage of development at trauma occurrence (e.g., childhood vs. adulthood), early pre-traumatic risk factors, or other individual differences. This study examined salivary cortisol levels at 08.00h and 16.00h as well as cortisol response to 0.50 mg DEX in 40 female Vietnam nurse veterans who had current, chronic PTSD (Current) vs. 43 who never had PTSD (Never). Repeated measures analyses of covariance did not reveal significant group differences in cortisol levels or cortisol suppression. Given that nurses who served in Vietnam had similar exposures, ages at exposure, and duration since exposure to previously studied male Vietnam combat veterans, the present lack of evidence for low cortisol and cortisol hyper-suppression in nurses with PTSD suggests that previous findings of low cortisol and cortisol hyper-suppression in male Vietnam veterans, females sexually abused as children, and other populations may reflect risk factors beyond simply having PTSD.

Introduction

As a unifying concept, post-traumatic stress disorder (PTSD) was intended to capture a universal response to any life-threatening event. Consequently, studies examining biological alterations in PTSD have not typically included subgroup analyses addressing whether the type of trauma exposure, chronicity of the PTSD, or other individual difference factors might explain heterogeneous biological findings (Yehuda, 2002, Yehuda, 2006). And, yet, the type of event to which the person has been exposed is (among other things) a potential source of individual variability that might explain different biological phenotypes in this disorder.

The earliest biological investigations in PTSD were performed in combat veterans, who seemed to be a prototypic PTSD group in that their symptom manifestations appeared to generalize to survivors of other types of traumatic exposures. The first published neuroendocrine study demonstrated significantly lower 24-h mean urinary cortisol excretion in Vietnam combat veterans with PTSD compared with veterans with other psychiatric disorders (Mason et al., 1986). To determine whether low cortisol levels reflected altered regulation of the hypothalamic-pituitary-adrenal axis, studies using the low dose dexamethasone suppression test (DST) were performed. Most found evidence for an exaggerated suppression of cortisol following 0.50 mg dexamethasone (DEX), reflecting a greater negative feedback inhibition in PTSD (reviewed in Yehuda, 2002).

With subsequent studies, discrepant observations about cortisol levels and, to a lesser degree, the cortisol response to DEX administration, emerged. Generally, evidence for lower basal urinary and plasma cortisol, and increased plasma cortisol suppression on the DST, has come from studies that compared relatively homogeneous PTSD and trauma-exposed groups (e.g., combat veterans, Holocaust survivors, victims of domestic violence, adult survivors of childhood sexual abuse, and children exposed to earthquakes) (e.g., Yehuda, 2002, Yehuda, 2005, Yehuda, 2006, Bremner et al., 2007, Heim et al., 2001, Griffin et al., 2005), whereas negative findings were more likely in studies in which more heterogeneous or epidemiological samples have been compared with a control group consisting of non-trauma-exposed persons without PTSD (Wessa et al., 2006, Young and Breslau, 2004a, Young and Breslau, 2004b, de Kloet et al., 2007). It may be that in the latter studies the “noise” associated with individual differences in gender, PTSD duration, type of exposure, and/or age overwhelms the neuroendocrine “signal” associated with PTSD. Alternatively, previously reported neuroendocrine correlates of PTSD might actually reflect specific PTSD risk factors. Consequently, the reliability and generality of cortisol findings is difficult to ascertain due to the sometimes substantive sample differences between studies that produce differing results.

Gender, in particular, is a potentially important mediator/moderator of basal cortisol levels and hyper-suppression of cortisol. There is some evidence suggesting that gender may be an important variable in differentiating different cortisol-related phenotypes. For example, Gill et al. (2005) observed that studies of male veterans have more consistently supported lower cortisol in PTSD than studies of females. However, studies of men have typically involved more chronic PTSD, thereby confounding gender and chronicity. The confounding of gender, trauma heterogeneity and PTSD chronicity makes it difficult to test which of these variables, or their combinations, contribute to cortisol alterations in PTSD.

The present study examined basal cortisol and cortisol suppression in a unique, homogeneous sample of female nurse veterans who served in Vietnam. This group closely paralleled previously studied male Vietnam combat veterans with respect to age at time of trauma (early adulthood), exposure to the culture of the Vietnam War experience, time elapsed since trauma, and duration of PTSD (30 + years). We hypothesized that female nurse Vietnam veterans with PTSD would show lower basal cortisol and higher cortisol suppression compared with nurse veterans without PTSD.