Pre-Existing High Glucocorticoid Receptor Number Predicting Development of Posttraumatic Stress Symptoms After Military Deployment

Department of Psychiatry , University Medical Center Utrecht, Utrecht, Utrecht, Netherlands
American Journal of Psychiatry (Impact Factor: 12.3). 11/2010; 168(1):89-96. DOI: 10.1176/appi.ajp.2010.10050706
Source: PubMed


The development of posttraumatic stress disorder (PTSD) is influenced by preexisting vulnerability factors. The authors aimed at identifying a preexisting biomarker representing a vulnerability factor for the development of PTSD. To that end, they determined whether the dexamethasone binding capacity of leukocytes, as a measure of glucocorticoid receptor (GR) number, before exposure to trauma was a predictor of development of PTSD symptoms. In addition, the authors analyzed mRNA expression for GR subtypes and GR target genes.
Participants were selected from a large prospective study on deployment-related disorders, in which peripheral blood mononuclear cells (PBMCs) were obtained prior to and 1 and 6 months after military deployment. Participants included armed forces personnel with high levels of PTSD symptoms 6 months after deployment (N=34) and comparison subjects without high levels of PTSD or depressive symptoms (N=34) matched for age, rank, previous deployments, educational level, and function during deployment.
Before military deployment, the GR number in PBMCs was significantly higher in participants who developed high levels of PTSD symptoms after deployment relative to matched comparison subjects. Logistic regression analysis showed that the risk for inclusion in the PTSD group after deployment increased 7.5-fold with each GR increase of 1,000. No group differences were observed in mRNA expression of GR-α, GR-P, GR-β, glucocorticoid-induced leucine zipper (GILZ), serum and glucocorticoid-inducible kinase-1 (SGK-1), and FKBP5. The higher GR number in the PTSD group was maintained at 1 and 6 months after deployment.
These results demonstrate that a preexisting high GR number in PBMCs is a vulnerability factor for subsequent development of PTSD symptoms.

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Available from: Elbert Geuze, Sep 09, 2015
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    • "This inhibitory signaling is mediated by glucocorticoid receptor proteins encoded by the gene NRC31 (DeRijk et al., 2008; McEwen, 2012; Meaney, 2001; Sapolsky, Romero, & Munck, 2000). Dysregulated glucocorticoid signaling disrupts HPA axis response to and recovery from a wide range of stressors, and has been implicated in child and adult manifestations of externalizing psychopathology (Fardet, Petersen, & Nazareth, 2012; Hawes, Brennan, & Dadds, 2009; Lopez-Duran et al., 2009; McBurnett et al., 1991; Savitz, Lucki, & Drevets, 2009; Stadler, Poustka, & Sterzer, 2010; van Zuiden et al., 2011). Particularly relevant to the current study is evidence that children exhibiting low cortisol reactivity to experimental challenge respond less favorably than high cortisol-reactive children to an intervention designed to reduce disruptive behavior (van de Wiel et al., 2004). "
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    • "The increased sensitivity of the HPA axis, including altered baseline cortisol levels and an increased sensitivity of the GR, can also be induced by adulthood trauma exposure independent of PTSD [22,23]. The increased sensitivity of GRs and the receptor expression may be a consequence of specific genetic backgrounds associated with GR genotypes [24,25]. Although a number of studies have also shown that GR polymorphisms are associated with changes in GCs sensitivity or altered cortisol [24,26,27], few studies have indicated that PTSD is associated with the presence of single nucleotide polymorphisms (SNPs) in genes associated with GR. "
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    • "At T1, exposure to combat stressors was assessed with a 13-item Deployment Stressors Checklist that was specifically developed for this study (Van Zuiden et al., 2011a). Items refer to specific events, for example " Exposure to enemy fire (yes/no) " , " Being the target of enemy fire (yes/no) " , and " Being held at gunpoint (yes/no) " . "
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