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Genome to Phenome: A Systems Biology Approach to PTSD Using an Animal Model

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Neuroproteomics

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1598))

Abstract

Post-traumatic stress disorder (PTSD) is a debilitating illness that imposes significant emotional and financial burdens on military families. The understanding of PTSD etiology remains elusive; nonetheless, it is clear that PTSD is manifested by a cluster of symptoms including hyperarousal, reexperiencing of traumatic events, and avoidance of trauma reminders. With these characteristics in mind, several rodent models have been developed eliciting PTSD-like features. Animal models with social dimensions are of particular interest, since the social context plays a major role in the development and manifestation of PTSD.

For civilians, a core trauma that elicits PTSD might be characterized by a singular life-threatening event such as a car accident. In contrast, among war veterans, PTSD might be triggered by repeated threats and a cumulative psychological burden that coalesced in the combat zone. In capturing this fundamental difference, the aggressor-exposed social stress (Agg-E SS) model imposes highly threatening conspecific trauma on naïve mice repeatedly and randomly.

There is abundant evidence that suggests the potential role of genetic contributions to risk factors for PTSD. Specific observations include putatively heritable attributes of the disorder, the cited cases of atypical brain morphology, and the observed neuroendocrine shifts away from normative. Taken together, these features underscore the importance of multi-omics investigations to develop a comprehensive picture. More daunting will be the task of downstream analysis with integration of these heterogeneous genotypic and phenotypic data types to deliver putative clinical biomarkers. Researchers are advocating for a systems biology approach, which has demonstrated an increasingly robust potential for integrating multidisciplinary data. By applying a systems biology approach here, we have connected the tissue-specific molecular perturbations to the behaviors displayed by mice subjected to Agg-E SS. A molecular pattern that links the atypical fear plasticity to energy deficiency was thereby identified to be causally associated with many behavioral shifts and transformations.

PTSD is a multifactorial illness sensitive to environmental influence. Accordingly, it is essential to employ the optimal animal model approximating the environmental condition that elicits PTSD-like symptoms. Integration of an optimal animal model with a systems biology approach can contribute to a more knowledge-driven and efficient next-generation care management system and, potentially, prevention of PTSD.

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Authors and Affiliations

  1. Integrative Systems Biology, Geneva Foundation, USACEHR, 568 Doughten Drive, Fredrick, MD, 21702-5010, USA

    Nabarun Chakraborty & James Meyerhoff

  2. Integrative Systems Biology, US Army Center for Environmental Health Research, USACEHR, 568 Doughten Drive, Frederick, MD, 21702-5010, USA

    Marti Jett & Rasha Hammamieh Ph.D.

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  1. Nabarun Chakraborty
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  2. James Meyerhoff
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  3. Marti Jett
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  4. Rasha Hammamieh Ph.D.
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Corresponding author

Correspondence to Rasha Hammamieh Ph.D. .

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Editors and Affiliations

  1. Department of Psychiatry, University of Florida McKnight Brain Institute, Gainesville, Florida, USA

    Firas H. Kobeissy

  2. Department of Cell Biology, Microbiology, & Molecular Biology, University of South Florida, Tampa, Florida, USA

    Stanley M. Stevens, Jr.

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Chakraborty, N., Meyerhoff, J., Jett, M., Hammamieh, R. (2017). Genome to Phenome: A Systems Biology Approach to PTSD Using an Animal Model. In: Kobeissy, F., Stevens, Jr., S. (eds) Neuroproteomics. Methods in Molecular Biology, vol 1598. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6952-4_6

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  • DOI: https://doi.org/10.1007/978-1-4939-6952-4_6

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6950-0

  • Online ISBN: 978-1-4939-6952-4

  • eBook Packages: Springer Protocols

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