Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

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

Lae Kim, Maria D’Orsogna, Tom Chou
doi: https://doi.org/10.1101/042887
Lae Kim
1Dept. of Biomathematics, Univ of California, Los Angeles, Los Angeles, USA.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maria D’Orsogna
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tom Chou
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

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 many 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. Crucially we find that the slow regulation mechanism mediates external stress-driven transitions between the stable states in novel, intensity, duration, and timing-dependent ways. These results indicate that the timing of traumatic events may be an important factor in determining if and how patients will exhibit hallmarks of stress disorders. Our model also suggests a mechanism whereby exposure therapy of stress disorders such as PTSD may act to normalize downstream dysregulation of the HPA axis.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted March 08, 2016.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Onset, timing, and exposure therapy of stress disorders: mechanistic insight from a mathematical model of oscillating neuroendocrine dynamics
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Onset, timing, and exposure therapy of stress disorders: mechanistic insight from a mathematical model of oscillating neuroendocrine dynamics
Lae Kim, Maria D’Orsogna, Tom Chou
bioRxiv 042887; doi: https://doi.org/10.1101/042887
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Onset, timing, and exposure therapy of stress disorders: mechanistic insight from a mathematical model of oscillating neuroendocrine dynamics
Lae Kim, Maria D’Orsogna, Tom Chou
bioRxiv 042887; doi: https://doi.org/10.1101/042887

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Physiology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4091)
  • Biochemistry (8772)
  • Bioengineering (6487)
  • Bioinformatics (23356)
  • Biophysics (11756)
  • Cancer Biology (9154)
  • Cell Biology (13257)
  • Clinical Trials (138)
  • Developmental Biology (7418)
  • Ecology (11376)
  • Epidemiology (2066)
  • Evolutionary Biology (15095)
  • Genetics (10403)
  • Genomics (14014)
  • Immunology (9126)
  • Microbiology (22070)
  • Molecular Biology (8783)
  • Neuroscience (47395)
  • Paleontology (350)
  • Pathology (1421)
  • Pharmacology and Toxicology (2482)
  • Physiology (3705)
  • Plant Biology (8054)
  • Scientific Communication and Education (1433)
  • Synthetic Biology (2211)
  • Systems Biology (6017)
  • Zoology (1250)