Mapping the network biology of metabolic response to stress in posttraumatic stress disorder and obesity.

Autor:	Chacko TP; Center for Clinical Systems Biology, Rochester General Hospital, Rochester, NY, United States.; Institute of Health Sciences and Technology, Rochester Institute of Technology, Rochester, NY, United States., Toole JT; Center for Clinical Systems Biology, Rochester General Hospital, Rochester, NY, United States.; Institute of Health Sciences and Technology, Rochester Institute of Technology, Rochester, NY, United States., Richman S; Center for Clinical Systems Biology, Rochester General Hospital, Rochester, NY, United States., Spink GL Jr; Rochester Regional Behavioral Health, Rochester, NY, United States., Reinhard MJ; War Related Illness and Injury Study Center, United States Department of Veterans Affairs, Washington, DC, United States., Brewster RC; War Related Illness and Injury Study Center, United States Department of Veterans Affairs, Washington, DC, United States., Costanzo ME; War Related Illness and Injury Study Center, United States Department of Veterans Affairs, Washington, DC, United States., Broderick G; Center for Clinical Systems Biology, Rochester General Hospital, Rochester, NY, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in psychology [Front Psychol] 2022 Jul 26; Vol. 13, pp. 941019. Date of Electronic Publication: 2022 Jul 26 (Print Publication: 2022).
DOI:	10.3389/fpsyg.2022.941019
Abstrakt:	The co-occurrence of stress-induced posttraumatic stress disorder (PTSD) and obesity is common, particularly among military personnel but the link between these conditions is unclear. Individuals with comorbid PTSD and obesity manifest other physical and psychological problems, which significantly diminish their quality of life. Current understanding of the pathways connecting stress to PTSD and obesity is focused largely on behavioral mediators alone with little consideration of the biological regulatory mechanisms that underlie their co-occurrence. In this work, we leverage prior knowledge to systematically highlight such bio-behavioral mechanisms and inform on the design of confirmatory pilot studies. We use natural language processing (NLP) to extract documented regulatory interactions involved in the metabolic response to stress and its impact on obesity and PTSD from over 8 million peer-reviewed papers. The resulting network describes the propagation of stress to PTSD and obesity through 34 metabolic mediators using 302 documented regulatory interactions supported by over 10,000 citations. Stress jointly affected both conditions through 21 distinct pathways involving only two intermediate metabolic mediators out of a total of 76 available paths through this network. Moreover, oxytocin (OXT), Neuropeptide-Y (NPY), and cortisol supported an almost direct propagation of stress to PTSD and obesity with different net effects. Although stress upregulated both NPY and cortisol, the downstream effects of both markers are reported to relieve PTSD severity but exacerbate obesity. The stress-mediated release of oxytocin, however, was found to concurrently downregulate the severity of both conditions. These findings highlight how a network-informed approach that leverages prior knowledge might be used effectively in identifying key mediators like OXT though experimental verification of signal transmission dynamics through each path will be needed to determine the actual likelihood and extent of each marker's participation. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Chacko, Toole, Richman, Spink, Reinhard, Brewster, Costanzo and Broderick.)
Databáze:	MEDLINE
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