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


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


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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