The biological subsystem interactions underlying the stress response of the human body: A dynamic modeling approach

Abstract

The dynamic stress response of the human body to stressors is produced by nonlinear interactions among its physiological subsystems. The evolutionary function of the response is to enable the body to cope with stress. However, depending on the level, duration, and frequency of the stressors, the mechanism may lose its function and the body can go into a pathological state. Three subsystems of the body play the most essential role in the stress response: endocrine, immune and neural systems. In this study, we construct a simulation model of these three subsystems to imitate the stress response dynamics under different types of external stimuli. Cortisol, glucocorticoid receptors, proinflammatory cytokines, serotonin, and serotonin receptors are the main variables of the model. Using both qualitative and quantitative physiological data, the model is structurally and behaviorally well-validated. Model’s capability of capturing the role of internal interactions in the system is authenticated with sensitivity analysis revealing bifurcations with respect to stress stimulus level and duration parameters. In subsequent scenario runs, we have successfully replicated the development of stress re lated abnormalities in the body. Depression-like dynamics, response sensitivity change as a result of earlier stress experience, and cytokine-induced sickness behavior are the real-life cases we simulate in this study. The model provides a quantitative represen tation of very well acknowledged qualitative hypotheses about the stress response of the body. This is a novel quantitative step towards the comprehension of stress re sponse in relation with other disorders, and it provides us with a tool to design and test treatment methods.