Higher Levels of Basal Serial CSF Cortisol in Combat Veterans With Posttraumatic Stress Disorder

VA San Diego Healthcare System, San Diego, California, United States
American Journal of Psychiatry (Impact Factor: 12.3). 06/2005; 162(5):992-4. DOI: 10.1176/appi.ajp.162.5.992
Source: PubMed

ABSTRACT Results of basal peripheral cortisol measures in posttraumatic stress disorder (PTSD) have been variable. The authors' goal was to measure CSF cortisol concentrations, which more accurately reflect brain glucocorticoid exposure, in subjects with or without PTSD.
CSF was withdrawn from a subarachnoid catheter and plasma from a venous catheter, both indwelling, over a 6-hour interval to determine hourly plasma ACTH and cortisol concentrations and hourly CSF cortisol levels in eight well-characterized combat veterans with PTSD and eight matched healthy volunteers.
Mean CSF cortisol concentrations were significantly higher in the subjects with PTSD (3.18 ng/ml, SD=0.33) than in the normal volunteers (2.33 ng/ml, SD=0.50), largely due to higher CSF cortisol concentration nadirs. No group differences were observed in either plasma ACTH or peripheral (plasma or urinary free) cortisol. CSF corticotropin-releasing hormone and CSF cortisol concentrations were positively and significantly correlated.
Despite normal peripheral cortisol indexes in the veterans with PTSD, their CNS exposure to cortisol was greater than that of normal comparison subjects.

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Available from: Thomas D Geracioti, Sep 18, 2015
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    • "Thus, studying the relationship between regulatory genes of the HPA axis and PTSD may be useful. There are many genes that influence HPA axis reactivity (Amstadter, Koenen, et al., 2009; Amstadter, Nugent, & Koenen, 2009; Koenen, 2007); however, CRH genes are seemingly particularly consequential (Baker et al., 2005; Smoller et al., 2005; Tyrka et al., 2009; van Gaalen, Stenzel-Poore, Holsboer, & Steckler, 2002). Of candidate gene studies of PTSD to date, few have examined genes influencing the HPA axis (Bachmann et al., 2005; Binder et al., 2008), with one prior study examining a CRH gene (Amstadter et al., 2011). "
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    Journal of anxiety disorders 08/2013; 27(7):678-683. DOI:10.1016/j.janxdis.2013.08.003 · 2.68 Impact Factor
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    • "F-S and F-R lines therefore provide a translational tool for identifying underlying determinants of fear memory strength as well as susceptibility and resistance to fearrelated psychopathology. Alterations in circadian corticosteroid rhythms are proposed endophenotypes of anxiety disorders, affective disorders, and PTSD (Baker et al., 2005; Wichers et al., 2008; Lok et al., 2012). In nonhuman primates, cortisol levels correlate with defensive freezing (Kalin et al., 1998), whereas in humans, higher basal cortisol levels are positively correlated with fear learning (Pineles et al., 2012), fear anticipation, amygdala activation (Grillon et al., 2006; Merz et al., 2012), and fear-potentiated startle (Grillon et al., 2006). "
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    European Journal of Neuroscience 08/2013; 38(9). DOI:10.1111/ejn.12337 · 3.18 Impact Factor
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    • "The finding of a blunted corticosterone response to acute footshock exposure is of particular interest. Studies have shown that a substantial corticosterone response is necessary for homeostatic adaptation to stressors (McEwen and Gianaros, 2010; Rao et al, 2012), and a pathologically blunted cortisol response to stress in humans is believed to contribute to disorders such as post-traumatic stress disorder (Baker et al, 2005; LaBar and Cabeza, 2006; Luo et al, 2012). Therefore, a blunted initial corticosterone response and a failure to show changes with repeated exposure could contribute to the pathological responses to stress seen in the MAM model. "
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