Chacko Thomas P, Toole J Tory, Richman Spencer, Spink Garry L, Reinhard Matthew J, Brewster Ryan C, Costanzo Michelle E, Broderick Gordon
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.
Front Psychol. 2022 Jul 26;13:941019. doi: 10.3389/fpsyg.2022.941019. eCollection 2022.
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.
应激诱导的创伤后应激障碍（PTSD）与肥胖症同时出现的情况很常见，尤其是在军事人员中，但这些病症之间的联系尚不清楚。患有PTSD和肥胖症合并症的个体还表现出其他身体和心理问题，这显著降低了他们的生活质量。目前对连接应激与PTSD和肥胖症的途径的理解主要集中在行为调节因子上，而很少考虑其同时出现背后的生物调节机制。在这项工作中，我们利用先验知识系统地突出这些生物行为机制，并为验证性试点研究的设计提供信息。我们使用自然语言处理（NLP）从超过800万篇同行评审论文中提取与应激代谢反应及其对肥胖症和PTSD的影响相关的已记录调节相互作用。由此产生的网络通过34种代谢调节因子描述了应激向PTSD和肥胖症的传播，使用了302种有超过10000次引用支持的已记录调节相互作用。应激通过21条不同的途径共同影响这两种病症，在通过该网络的总共76条可用途径中，仅涉及两种中间代谢调节因子。此外，催产素（OXT）、神经肽Y（NPY）和皮质醇支持应激向PTSD和肥胖症的几乎直接传播，但具有不同的净效应。虽然应激上调了NPY和皮质醇，但据报道这两种标志物的下游效应均可减轻PTSD的严重程度，但会加重肥胖症。然而，发现应激介导的催产素释放会同时下调这两种病症的严重程度。这些发现突出了一种利用先验知识的网络信息方法如何能够有效地用于识别像OXT这样的关键调节因子，不过需要通过实验验证每条途径的信号传递动态，以确定每个标志物参与的实际可能性和程度。
