Cortisol suppression by dexamethasone reduces exaggerated fear responses in posttraumatic stress disorder

Emory University School of Medicine, Department of Psychiatry and Behavioral Sciences, Atlanta, GA 30303, United States.
Psychoneuroendocrinology (Impact Factor: 4.94). 05/2011; 36(10):1540-52. DOI: 10.1016/j.psyneuen.2011.04.008
Source: PubMed


PTSD symptoms are associated with heightened fear responses in laboratory fear conditioning paradigms. This study examined the effects of dexamethasone administration on hypothalamic-pituitary-adrenal (HPA) function and fear-potentiated startle (FPS) in trauma-exposed individuals with and without PTSD. We used an established fear discrimination procedure, in which one visual stimulus (CS+, danger cue) was paired with aversive airblasts to the throat (unconditioned stimulus, US), and another stimulus (CS-, safety cue) was presented without airblasts. In addition to FPS, the dexamethasone suppression test (DST) was performed. The study sample (N=100) was recruited from a highly traumatized civilian population in Atlanta, GA. Half of the subjects (n=54, 16 PTSD, 38 controls) underwent conditioning at baseline and the other half (n=46, 17 PTSD, 29 controls) after DST, in a cross-sectional design. We found a significant interaction effect of diagnostic group and dexamethasone treatment. Under baseline conditions, subjects with PTSD showed more than twice as much fear-potentiated startle to the danger cue compared to traumatized controls, F(1,53)=8.08, p=0.006. However, there was no group difference in subjects tested after dexamethasone suppression. Furthermore, there was a significant treatment effect in PTSD subjects but not in controls, with dexamethasone reducing fear-potentiated startle to the CS+, F(1,32)=4.00, p=0.05. There was also a positive correlation between PTSD subjects' FPS and cortisol levels, r=0.46, p=0.01. These results suggest that transient suppression of HPA function via dexamethasone suppression may reduce exaggerated fear in patients with PTSD.

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Available from: Kerry Ressler, Sep 16, 2014
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    • "Inconsistency in measurement of cortisol (e.g., diurnal vs. baseline vs. reactivity, plasma vs. saliva, etc.) may account for variability in sex-related findings (Olff, Langeland, Draijer, & Gersons, 2007). Cortisol itself may have an effect on fear learning, with different patterns for males and females (Jovanovic et al., 2011; Van Ast, Vervliet, & Kindt, 2012). Thus, it would seem that both biological propensities and social constructions maintain this gender disparity. "
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    • "In addition to its role in emotional behaviors, the BNST also regulates hypothalamic–pituitary–adrenal (HPA) activity (Cullinan et al. 1993; Gray et al. 1993; Herman et al. 1994; Herman and Cullinan 1997; Sullivan et al. 2004; Choi et al. 2007, 2008a,b; Green et al. 2007). Because intra-BNST CGRP infusions increase fos immunoreactivity in the paraventricular nucleus of the hypothalamus (Sink et al. 2011)—a nodal point in the HPA axis—and because HPA activity can influence fear learning and expression (Roozendaal 2002; Aerni et al. 2004; Donley et al. 2005; Schelling et al. 2006; Soravia et al. 2006; Tronel and Alberini 2007; Taubenfeld et al. 2009; Jovanovic et al. 2011; Zohar et al. 2011; Atsak et al. 2012; de Oliveira et al. 2013), we also examined the contribution of BNST CGRP receptors to shockinduced corticosterone release. "
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    • "Besides the already mentioned causal link to SAM hyperdrive, a larger startle response was found to be positively associated with cortisol levels and negatively associated with the steroid hormone dehydroepiandrosterone (DHEA-S) [81]. Interestingly, cortisol suppression by dexamethasone reduces exaggerated startle responses in PTSD patients [82]. "
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