Altered gene expression of the innate immune, neuroendocrine, and nuclear factor-kappa B (NF-κB) systems is associated with posttraumatic stress disorder in military personnel

Pedro Guardado; Anlys Olivera; Heather L Rusch; Michael Roy; Christiana Martin; Natasha Lejbman; Hwyunhwa Lee; Jessica M Gill

doi:10.1016/j.janxdis.2015.12.004

Altered gene expression of the innate immune, neuroendocrine, and nuclear factor-kappa B (NF-κB) systems is associated with posttraumatic stress disorder in military personnel

J Anxiety Disord. 2016 Mar:38:9-20. doi: 10.1016/j.janxdis.2015.12.004. Epub 2015 Dec 10.

Authors

Pedro Guardado¹, Anlys Olivera¹, Heather L Rusch², Michael Roy³, Christiana Martin¹, Natasha Lejbman¹, Hwyunhwa Lee⁴, Jessica M Gill⁵

Affiliations

¹ National Institute of Nursing Research, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
² National Institute of Nursing Research, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA; Henry M Jackson Foundation for The Advancement of Military Medicine, 6720A Rockledge Drive #100, Bethesda, MD 20817, USA.
³ Uniformed Service University of the Health Science, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
⁴ University of Nevada, Las Vegas, School of Nursing, 4505 South Maryland Parkway, Las Vegas, NV 89154, USA.
⁵ National Institute of Nursing Research, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA. Electronic address: [email protected].

PMID: 26751122
DOI: 10.1016/j.janxdis.2015.12.004

Abstract

Whole transcriptome analysis provides an unbiased examination of biological activity, and likely, unique insight into the mechanisms underlying posttraumatic stress disorder (PTSD) and comorbid depression and traumatic brain injury. This study compared gene-expression profiles in military personnel with PTSD (n=28) and matched controls without PTSD (n=27) using HG-U133 Plus 2.0 microarrays (Affymetrix), which contain 54,675 probe sets representing more than 38,500 genes. Analysis of expression profiles revealed 203 differentially expressed genes in PTSD, of which 72% were upregulated. Using Partek Genomics Suite 6.6, differentially expressed transcription clusters were filtered based on a selection criterion of ≥1.5 relative fold change at a false discovery rate of ≤5%. Ingenuity Pathway Analysis (Qiagen) of the differentially expressed genes indicated a dysregulation of genes associated with the innate immune, neuroendocrine, and NF-κB systems. These findings provide novel insights that may lead to new pharmaceutical agents for PTSD treatments and help mitigate mental and physical comorbidity risk.

Keywords: Gene expression; Innate immune; NF-κB; Neuroendocrine; PTSD; Trauma.

MeSH terms

Adult
Brain Injuries / epidemiology
Case-Control Studies
Comorbidity
Depression / epidemiology
Female
Gene Expression Profiling
Gene Expression Regulation*
Humans
Immunity, Innate / genetics*
Immunity, Innate / physiology
Male
Military Personnel / psychology*
Military Personnel / statistics & numerical data
NF-kappa B / genetics*
NF-kappa B / physiology
Neurosecretory Systems / physiopathology*
Stress Disorders, Post-Traumatic / epidemiology
Stress Disorders, Post-Traumatic / genetics*

Substances

NF-kappa B