Hypothalamic-pituitary-adrenocortical axis dysfunction in epilepsy

Physiol Behav. 2016 Nov 1:166:22-31. doi: 10.1016/j.physbeh.2016.05.015. Epub 2016 May 16.


Epilepsy is a common neurological disease, affecting 2.4million people in the US. Among the many different forms of the disease, temporal lobe epilepsy (TLE) is one of the most frequent in adults. Recent studies indicate the presence of a hyperactive hypothalamopituitary- adrenocortical (HPA) axis and elevated levels of glucocorticoids in TLE patients. Moreover, in these patients, stress is a commonly reported trigger of seizures, and stress-related psychopathologies, including depression and anxiety, are highly prevalent. Elevated glucocorticoids have been implicated in the development of stress-related psychopathologies. Similarly, excess glucocorticoids have been found to increase neuronal excitability, epileptiform activity and seizure susceptibility. Thus, patients with TLE may generate abnormal stress responses that both facilitate ictal discharges and increase vulnerability for the development of comorbid psychopathologies. Here, we will examine the evidence that the HPA axis is disrupted in TLE, consider potential mechanisms by which this might occur, and discuss the implications of HPA dysfunction for seizuretriggering and psychiatric comorbidities.

Keywords: CRH; Glucocorticoids; Psychopathologies; Stress; Temporal lobe epilepsy.

Publication types

  • Review

MeSH terms

  • Endocrine System Diseases / epidemiology
  • Endocrine System Diseases / etiology*
  • Epilepsy / complications*
  • Epilepsy / epidemiology
  • Humans
  • Hypothalamo-Hypophyseal System / physiopathology*
  • Pituitary-Adrenal System / physiopathology*