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Article Excerpt
POSTTRAUMATIC STRESS DISORDER (PTSD) is a stress-related disorder that affects approximately 8% of individuals in the United States and is commonly comorbid with alcohol-use disorders (Kessler et al., 1995). Clinical observations, animal models, and prominent theories of addiction implicate stress as a contributing factor in the initiation or maintenance of substance-use disorders (Goeders, 2003; Karlsgodt et al., 2003; Kreek and Koob, 1998; Stewart, 1996). Although underlying mechanisms by which stress contributes to substance use are unclear, animal models of stress-induced relapse implicate activity of the hypothalamic-pituitary-adrenal (HPA) axis, one of the main hormonal systems involved in the response to stress. Dysregulation of the HPA axis response is found in both PTSD and alcohol dependence and may provide a mechanistic link between these two disorders.
Dysregulation of HPA axis function is hypothesized to be an important factor in the pathophysiology of PTSD (Vermetten and Bremner, 2002). Although the data across studies are somewhat inconsistent, corticotropin-releasing hormone (CRH) is increased in individuals with PTSD (Bremner et al., 1997), and several studies have demonstrated blunted adrenal corticotropic hormone (ACTH) and cortisol response to CRH in individuals with PTSD (De Bellis et al., 1994; Smith et al., 1989). The response to other provocative stimuli is less consistent, with some studies showing decreased (Liberzon et al., 1999) and others increased ACTH and cortisol response to a variety of provocative stimuli in individuals with PTSD (Bremner et al., 2003; Heim et al., 2000).
Interestingly, unlike individuals with major depression, individuals with PTSD may have normal or decreased basal cortisol levels (Heim et al., 1998; Resnick et al., 1995; Yehuda et al., 1993), and several studies suggest increased sensitivity of the pituitary gland to negative feedback from cortisol (Yehuda et al., 1993). As such, individuals with PTSD may have high CRH levels with low or normal ACTH and cortisol levels. In animal models, increased CRH has an anxiety-inducing effect (Koob and Britton, 1996), and CRH antagonists have been shown to prevent stress-induced relapse to drug-seeking behavior in rats (Erb et al., 1998).
Chronic alcohol consumption is also associated with abnormalities in HPA axis function. Although increased ACTH or cortisol secretion is typically seen during acute alcohol withdrawal (Kirkman and Nelson, 1988), abstinent alcohol-dependent individuals after the acute withdrawal period demonstrate an attenuated ACTH and cortisol response to a variety of stimuli, including chemical challenge, mental arithmetic, cold pressor, and isometric handgrip. Whether these neuroendocrine abnormalities in abstinent individuals are biological markers of underlying susceptibility to alcohol dependence or the result of chronic exposure to alcohol is unknown. It is possible that HPA axis abnormalities are involved in vulnerability to relapse, and this may be particularly important for individuals with comorbid alcohol dependence and PTSD.
Despite the relatively high comorbidity of PTSD and alcohol dependence and evidence that HPA abnormalities are associated with both disorders, there are no studies of HPA axis function in individuals with comorbid PTSD and alcohol dependence. The cold pressor task (CPT) is a coldwater immersion task that has been used in a number of studies to test sympathetic nervous and HPA activity (Peters et al., 1998; Vescovi et al., 1997). Because HPA axis abnormalities may provide a mechanistic link between PTSD and alcohol dependence, this study sought to address the gap in the research literature concerning comorbid PTSD and alcohol dependence by investigating the response to a classic HPA axis challenge paradigm (CPT) in men and women with PTSD only, PTSD and comorbid alcohol dependence, alcohol dependence only, and a control group. The hypothesis to be tested was that individuals with comorbid PTSD and alcohol dependence would experience a greater disturbance HPA axis response to the CPT than individuals with either PTSD or alcohol dependence alone.
Method
Research participants
Participants were men and women ages 18-60 years recruited primarily via media advertisements over a 36-month period for a human laboratory study of the impact of acute treatment with an opiate antagonist on HPA axis response in individuals with alcohol dependence and PTSD. Each participant was scheduled for two laboratory sessions. Data from the first session are presented in this study. After the first session, individuals were randomized to receive 50 mg of naltrexone or placebo for 7 days after which a second session was scheduled. Participants were placed in the following diagnostic groups based on a structured clinical interview: alcohol dependence and PTSD (n = 28), alcohol dependence and no current or lifetime PTSD (n = 31), PTSD and no current or lifetime alcohol-use disorder (n = 30), and no current or history of PTSD or an alcohol-use disorder (control group; n = 30). Following a brief telephone screening, candidates were scheduled for a clinical interview to assess eligibility requirements. The study was fully explained...
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