Onset, Timing, and Exposure Therapy of Stress Disorders: Mechanistic Insight from a Mathematical Model of Oscillating Neuroendocrine Dynamics (Open Access)
Abstract
Background: 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 a 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) .Results: 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. Conclusion: Our two-step negative feedback model suggests a mechanism whereby exposure therapy of stress disorders such as PTSD may act to normalize downstream dysregulation of the HPA axis. Our analysis provides a causative rationale for improving treatments and guiding the design of new protocols.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 25, 2016
- Accession Number
- AD1042163
Entities
People
- Lae U. Kim
- Maria R D'Orsogna
- Tom Chou
Organizations
- University of California, Los Angeles