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Open Access Research article

Core modular blood and brain biomarkers in social defeat mouse model for post traumatic stress disorder

Ruoting Yang156, Bernie J Daigle Jr2, Seid Y Muhie5, Rasha Hammamieh5, Marti Jett5, Linda Petzold123 and Francis J Doyle14*

Author Affiliations

1 Institute for Collaborative Biotechnologies, University of California Santa Barbara, Santa Barbara, CA 93106-5080, USA

2 Department of Computer Science, University of California Santa Barbara, Santa Barbara, CA 93106-5080, USA

3 Department of Mechanical Engineering, University of California Santa Barbara, Santa Barbara, CA 93106-5080, USA

4 Department of Chemical Engineering, University of California Santa Barbara, Santa Barbara, CA 93106-5080, USA

5 US Army Center for Environmental Health Research, Fort Detrick, MD, 21702-5010, USA

6 Advanced Biomedical Computing Center, Frederick National Laboratory for Cancer Research, Frederick, MD 21702-5010, USA

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BMC Systems Biology 2013, 7:80  doi:10.1186/1752-0509-7-80

Published: 20 August 2013

Abstract

Background

Post-traumatic stress disorder (PTSD) is a severe anxiety disorder that affects a substantial portion of combat veterans and poses serious consequences to long-term health. Consequently, the identification of diagnostic and prognostic blood biomarkers for PTSD is of great interest. Previously, we assessed genome-wide gene expression of seven brain regions and whole blood in a social defeat mouse model subjected to various stress conditions.

Results

To extract biological insights from these data, we have applied a new computational framework for identifying gene modules that are activated in common across blood and various brain regions. Our results, in the form of modular gene networks that highlight spatial and temporal biological functions, provide a systems-level molecular description of response to social stress. Specifically, the common modules discovered between the brain and blood emphasizes molecular transporters in the blood-brain barrier, and the associated genes have significant overlaps with known blood signatures for PTSD, major depression, and bipolar disease. Similarly, the common modules specific to the brain highlight the components of the social defeat stress response (e.g., fear conditioning pathways) in each brain sub-region.

Conclusions

Many of the brain-specific genes discovered are consistent with previous independent studies of PTSD or other mental illnesses. The results from this study further our understanding of the mechanism of stress response and contribute to a growing list of diagnostic biomarkers for PTSD.