Recalibrating 'Fight Or Flight'

Main Category: Biology / Biochemistry
Article Date: 23 Jan 2009 - 4:00 PDT

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A Canadian/U.S. research team has reported a novel approach to stimulating recovery from chronic stress disorders. Details of the therapeutic model, which exploits the natural dynamics of the body's "fight or flight" system, are published January 23 in the open-access journal PLoS Computational Biology. In contrast to conventional time-invariant therapy, the researchers propose a well-directed therapeutic push delivered according to an optimal treatment schedule.

The hypothalamic, pituitary, adrenal (HPA) axis constitutes one of the body's major control systems, serving to maintain body homeostasis with hormone feedback regulatory loops. If the HPA axis is driven very far from its natural homeostatic rest point, it may be unable to fully recover the healthy physiologic state. Under such conditions, the HPA axis dysfunction may become chronic. HPA axis dysfunction has been characterized in disorders including Chronic Fatigue Syndrome (CFS), depression, post- traumatic stress disorder and Alzheimer disease.

The research team, consisting of Drs. Amos Ben-Zvi, Suzanne D. Vernon, and Gordon Broderick, used a relatively simple mathematical description of the HPA axis to show how the complex dynamical behavior of this system could accommodate multiple stable resting states; some corresponding to chronic loss of function characterized by low cortisol, a hormone that modulates immune function. A robust treatment strategy was designed to take advantage of the body's existing homeostatic mechanism, using a short-duration intervention to assist the HPA axis in re-asserting homeostasis about a healthy equilibrium. Akin to pulling back a slingshot, temporarily reducing the bioavailability of cortisol pharmacologically causes the HPA axis to overcompensate and launch itself back into a correct regulatory regime.

The Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia estimates that between 1 and 4 million Americans suffer from CFS, and only half have consulted a physician for their illness. The CDC and DePaul University have estimated CFS costs the US economy approximately $30 billion each year in health care and lost productivity.

The researchers propose a theoretical, single intervention therapeutic model that is counter-intuitive and challenges the conventional time-invariant approach to many therapies. Validation of this model will require clinical collaboration.

CITATION:
"Model-Based Therapeutic Correction of Hypothalamic-Pituitary-Adrenal Axis Dysfunction."
Ben-Zvi A, Vernon SD, Broderick G (2009)
PLoS Comput Biol 5(1): e1000273. doi:10.1371/journal.pcbi.1000273
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