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Stress and Epilepsy: Multiple Models, Multiple Outcomes

Sawyer, Nikki T.; Escayg, Andrew

Journal of Clinical Neurophysiology: December 2010 - Volume 27 - Issue 6 - p 445-452
doi: 10.1097/WNP.0b013e3181fe0573
Invited Review

Human studies show a link between stress and epilepsy, with stress causing an increase in seizure frequency and severity in patients with epilepsy. Many different animal model systems have been used to better understand this connection and the possible mechanisms involved. This review highlights the results of such studies relating stress and seizure susceptibility, with a focus on the hypothalamic-pituitary-adrenal axis and its relationship to seizure generation. The effects of hypothalamic-pituitary-adrenal axis mediators, acute stress, chronic stress, and early life stress on the seizure phenotype are summarized. Results suggest that stress has both anticonvulsive and proconvulsive properties, depending on the animal strain and the stress/seizure induction paradigm used. Attempts to interpret the stress-epilepsy literature must take these variables into account. The growing availability of genetically modified mice that carry either human epilepsy mutations or mutations in stress pathway genes now provide the opportunity to examine the relationship between stress and epilepsy more directly.

From the Department of Human Genetics, Emory University, Atlanta, Georgia, U.S.A.

Supported by National Institutes of Health grants NS066155 and NS065187 (to A.E.) and a predoctoral training grant T32 GM 08605-13 (to N.T.S.).

Address correspondence and reprint requests to Andrew Escayg, PhD, Department of Human Genetics, Emory University, 615 Michael Street, Whitehead Building, Suite 301, Atlanta, GA 30322, U.S.A.; e-mail:

Copyright © 2010 American Clinical Neurophysiology Society