Mar 26, 2016

Onset, timing, and exposure therapy of stress disorders: mechanistic insight from a mathematical model of oscillating neuroendocrine dynamics

Biology Direct
Lae U KimTom Chou

Abstract

The hypothalamic-pituitary-adrenal (HPA) axis is a neuroendocrine system that regulates numerous physiological processes. Disruptions in the activity of the HPA axis are correlated with stress-related diseases such as post-traumatic stress disorder (PTSD) and major depressive disorder. In this paper, we characterize "normal" and "diseased" states of the HPA axis as basins of attraction of a dynamical system describing the inhibition of peptide hormones such as corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) by circulating glucocorticoids such as cortisol (CORT). In addition to including key physiological features such as ultradian oscillations in cortisol levels and self-upregulation of CRH neuron activity, our model distinguishes the relatively slow process of cortisol-mediated CRH biosynthesis from rapid trans-synaptic effects that regulate the CRH secretion process. We show that the slow component of the negative feedback allows external stress-induced reversible transitions between "normal" and "diseased" states in novel intensity-, duration-, and timing-dependent ways. Our two-step negative feedback model suggests a mechanism whereby exposure therapy of stress disorders such as PTSD may act to ...Continue Reading

  • References57
  • Citations2

Citations

Mentioned in this Paper

Corticosterone Assay
Biochemical Pathway
Biological Adaptation to Stress
Ultradian Rhythm
Coombs Test
Growth Hormone Activity
Human Platelet Antigens
Neuroendocrine Tumors
Physiologic Pulse
Pituitary Hormones, Anterior

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