Corticotrophin-Releasing Hormone Type 1 Receptor Gene (CRHR1) Variants Predict Posttraumatic Stress Disorder Onset and Course in Pediatric Injury Patients

Ananda B Amstadter,Nicole R Nugent,Jordan W Smoller,Alisa Miller,Glenn Saxe,Jesen Fagerness,Aditi Basu,Richie Siburian,Bao-Zhu Yang,Stephen Haddad,Priya Moorjani,Karestan C Koenen

doi:10.1155/2011/928497

Abstract

Posttraumatic stress disorder (PTSD) is a common and disabling anxiety disorder that may occur in the aftermath of exposure to potentially traumatic life events. PTSD is moderately heritable, but few specific molecular variants accounting for this heritability have been identified. Genes regulating the hypothalamic-pituitary-adrenal (HPA) axis, such as corticotrophin-releasing hormone type 1 receptor gene (CRHR1), have been implicated in traumatic-stress related phenotypes but have yet to be studied in relation to PTSD. The present study sought to examine the relation between 9 single nucleotide polymorphisms (SNPs) in theCRHR1gene and posttraumatic stress symptoms in a prospective study of pediatric injury patients (n= 103) who were first assessed in the acute aftermath of their injury at the hospital. Results indicated that multiple SNPs were associated with acute symptoms at a univariate level, and after correction for multiple testing, rs12944712 was significantly related to acute PTSD symptoms. Longitudinal latent growth curve analyses suggest that rs12944712 is also related to both acute symptom level and trajectory of symptoms over time. The present study adds support for the role ofCRHR1in the stress response following potentially traumatic event exposure in youth. It should be noted that the sample size in this study was small, and therefore statistical power was low; following, results from this study should be considered preliminary. Although results are not definitive, the findings from this study warrant future replication studies on how variation in this gene relates to response to traumatic event exposure in youth.

Highlights

Stressful experiences involve the recruitment of the body’s major stress systems, including the hypothalamic-pituitary-adrenal (HPA) axis
As we have argued elsewhere [25], genes implicated in the development or onset of symptoms of posttraumatic stress disorder (PTSD) may differ from genes implicated in the maintenance or course of symptoms of PTSD
Results suggest that polymorphisms in the corticotrophinreleasing hormone type 1 receptor gene (CRHR1) gene, which is involved in activation of the HPA pathway, are related to acute PTSD symptoms in pediatric injury patients

Summary

Introduction

Stressful experiences involve the recruitment of the body’s major stress systems, including the hypothalamic-pituitary-adrenal (HPA) axis. The HPA axis, activated by corticotrophin-releasing hormone (CRH), regulates the release of stress hormones such as cortisol [1]. In many individuals, this normative stress response is followed by a return to baseline once the stressor has passed. There is reason to hypothesize that genes regulating the HPA axis would be relevant to study in relation to posttraumatic stress symptom trajectory. These findings suggest that the HPA axis may be dysregulated in individuals with PTSD, but they are not specific to PTSD. Many phenotypes are common following exposure to traumatic events, such as depression and other anxiety disorders, and many of these disorders evidence HPA axis dysregulation

Results

Discussion

Conclusion