Transcriptional control of monocyte gene expression in post-traumatic stress disorder

Issue title: Molecular Biology of Post Traumatic Stress Disorder

Article type: Research Article

Authors: O'Donovan, Aoife^{; ;} | Sun, Bing^{; ;} | Cole, Steve | Rempel, Hans^; | Lenoci, Maryann^{; ;} | Pulliam, Lynn^{; ;} | Neylan, Thomas^{; ;}

Affiliations: Veteran's Affairs Medical Center, San Francisco, CA, USA | Northern California Institute for Research and Education, San Francisco, CA, USA | Department of Psychiatry, University of California, San Francisco, CA, USA | Department of Laboratory Medicine, University of California, San Francisco, CA, USA | Department of Medicine, University of California, Los Angeles, CA, USA

Note: [] Corresponding author: Aoife O'Donovan, Department of Psychiatry, University of California, San Francisco, San Francisco Veteran's Affairs Medical Center, San Francisco CA 94121, USA. Tel.: +1 415 221 4810 (Extn: 4959); E-mail: aoife.odonovan@ucsf.edu

Abstract: Post-traumatic stress disorder (PTSD) confers an increased risk for disorders with an inflammatory etiology. PTSD-related dysregulation of the sympathetic nervous system (SNS) and hypothalamic-pituitary adrenal (HPA) axis and associated alterations in inflammatory activity may contribute to this increased risk. However, little is known about convergent SNS, HPA and inflammatory signaling at the level of the immune cell transcriptome in PTSD. To explore such signaling, we examined the prevalence of specific transcription factor binding motifs in the promoter regions of differentially expressed genes in monocytes from individuals with PTSD and matched controls. Participants included 49 men (24 PTSD+ and 25 trauma-exposed controls) and 18 women (10 PTSD+ and 8 controls). Men with PTSD showed up-regulation of target genes for the NF-κB/Rel family of transcription factors, which convey inflammatory signals, up-regulation of target genes for CREB/ATF transcription factors, which convey adrenergic signals from the SNS, and down-regulation of target genes for the glucocorticoid receptor, which conveys glucocorticoid signals from the HPA axis. Women with PTSD also showed significant up-regulation of target genes for NF-κB and non-significant down-regulation of target genes for GR, but significant down-regulation of target genes for CREB/ATF. Altered transcriptional control of monocyte gene expression could contribute to exaggerated inflammatory activity in PTSD.

DOI: 10.3233/DMA-2011-0768

Journal: Disease Markers, vol. 30, no. 2-3, pp. 123-132, 2011