PTSD and the HPA axis: Differences in response to the cold pressor task among individuals with child vs. adult trauma

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Summary

Hypothalamic pituitary adrenal (HPA) axis and subjective stress response to a cold-water immersion task, the cold pressor task (CPT), in individuals (N=89) with post-traumatic stress disorder (PTSD) were examined. All tests were conducted at 08:00 h after an overnight hospital stay. Plasma adrenocorticotrophin hormone (ACTH), cortisol, and subjective stress were examined at baseline and five post-task time points in controls (n=31), subjects with PTSD as a result of an index trauma during childhood (i.e. before age 18; n=25), and subjects with PTSD as a result of an index trauma as an adult (n=33). Approximately, 50% of individuals in both trauma groups were alcohol dependent, and the impact of this comorbidity was also examined. Subjects with PTSD, regardless of age of index trauma, had a less robust ACTH response as compared to controls. Regardless of the presence or absence of comorbid alcohol dependence, subjects with childhood trauma had lower cortisol at baseline and at all post-task measurement points and did not demonstrate the decrease in cortisol over the course of the 2 h monitoring period seen in subjects with adult index trauma and controls. The findings reveal differences in the neuroendocrine response to the CPT in individuals with PTSD compared to control subjects, and differences in PTSD subjects when examined by age of index trauma.

Introduction

There has been much progress made in the past 20 years in understanding the neurobiology of post-traumatic stress disorder (PTSD). The hypothalamic pituitary adrenal (HPA) axis has been the focus of many investigations and inconsistencies in study findings emphasize both the heterogeneity of PTSD and the complexity of the regulation of the HPA axis (Yehuda, 2002). Discrepancies in the literature concerning HPA function in individuals with PTSD are likely to be the result of differences in the experimental paradigm utilized, sample collection timing or procedures and/or characteristics of the individuals being studied.

In this regard, one interesting area is the comparison of individuals traumatized during childhood to those traumatized as adults. A number of preclinical and clinical studies suggest that early life stress is associated with long-lasting neurobiologic changes that may predispose to the development of depression, anxiety disorders and substance use disorders (DeBellis et al., 1999, Heim and Nemeroff, 2001). As such, there may be differences in the neurobiologic profile of individuals with PTSD depending on the timing of the index trauma which could help to explain heterogeneity of results across studies. Yehuda et al. (2001) found an inverse relationship between childhood emotional abuse and serum cortisol levels in adult children of Holocaust survivors. However, Young et al. (2004) recently reported finding no differences in salivary cortisol levels between women with childhood and adulthood trauma.

PTSD is often comorbid with substance use disorders and other psychiatric disorders (Jacobsen et al., 2001). This comorbidity may impact neurobiology and contribute to discrepancies in the literature. In a series of studies of HPA axis function in women with a history of childhood abuse, the cortisol and ACTH response varied depending on the presence or absence of depression and on the experimental paradigm used (Heim and Nemeroff, 2001, Heim et al., 2000, Heim et al., 2001). PTSD and alcohol use disorders are also commonly comorbid. Chronic alcohol consumption is also associated with abnormalities in the HPA axis response (Adinoff et al., 2005, Bernardy et al., 1996, Errico et al., 1993, Gianoulakis et al., 2003, Krystal et al., 1996). While increased ACTH/cortisol secretion is typically seen during acute alcohol withdrawal (Kirkman and Nelson, 1988), alcohol dependent individuals who have been abstinent for up to 1 month demonstrate an attenuated ACTH and cortisol response to a variety of stressors including chemical challenge, mental arithmetic, cold pressor, and isometric handgrip (Adinoff et al., 2005, Bernardy et al., 1996). The impact of comorbid alcohol dependence on HPA axis function in individuals with PTSD has not been studied.

The present study is a subanalysis of a larger study of HPA axis response to a classic physical stress task, the Cold Pressor Task (CPT), in individuals with PTSD, alcohol dependence and PTSD, and controls. Individuals with current major depression were excluded to allow for the study of the interaction of PTSD and alcohol use, without the confound of depression. The stressor employed in this study is a cold-water immersion task that has been used in a number of studies to test sympathetic nervous and HPA reactivity (Peters et al., 1998, Velasco et al., 1997, Victor et al., 1987). Much of the work using provocative tests in individuals with PTSD has employed pharmacologic probes and psychological stressors, so it was reasoned that response to a well-defined physical stressor might contribute further to our understanding of PTSD. In this analysis, we primarily investigated the impact of age of index trauma on the neuroendocrine and subjective stress response to the CPT.

Section snippets

Participants

The sample included men (n=43) and women (n=46), aged 18–60 years, with PTSD (n=58), and a control group (n=31). For this analysis, subjects were divided into two groups: individuals with PTSD as a result of an index trauma during childhood (i.e. before age 18; n=25) and individuals with PTSD as a result of an index trauma as an adult (n=33). Twenty-eight individuals with PTSD also met criteria for alcohol dependence. Thirteen alcohol-dependent subjects were in the childhood trauma group and 15

Demographic comparisons

Table 1 presents the demographic and clinical characteristics of the 89 participants divided by age of index trauma. As can be seen, the groups were equivalent on all demographic and clinical characteristics except age. For the childhood trauma vs. adult trauma groups, there were no significant differences on measures of baseline PTSD symptoms or alcohol dependence/use.

Cortisol

Panel A of Fig. 1 depicts the childhood trauma, adult trauma, and control group mean cortisol values adjusted for age and

Discussion

In this study, the impact of age at the time of index trauma (childhood vs. adult) and the presence of comorbid alcohol dependence on neuroendocrine and subjective response to the CPT in individuals with PTSD was investigated. PTSD symptoms and alcohol use indices were also examined. Of interest, there were few differences in clinical presentation of PTSD or alcohol dependence between groups. This is in contrast to one study that demonstrated that women with a history of childhood abuse were

Acknowledgements

This study was completed with grant support from NIAAA no.2P50AA10761 and the General Clinical Research Center USPHS Grant no.M01RR01070.

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