Impairment of inhibitory control of the hypothalamic pituitary adrenocortical system in epilepsy

Abstract

Excess comorbidity between depression and epilepsy proposes common pathophysiological patterns in both disorders. Neuroendocrine abnormalities were often observed in depression as well as in epilepsy. Lack of inhibitory control of the hypothalamic pituitary adrenocortical (HPA) system is a core feature of depression; main relay stations of this system are located in the amygdala and hippocampus, which are key regions for both disorders. Therefore we explored the feedback mechanism of the HPA system in epilepsy. In order to control for the impact of depression we focused on epilepsies without depression. We compared patients with epilepsy (subdivided by medication with or without hepatic enzyme inducing antiepileptic medication) with 16 healthy controls and 16 patients with unipolar major depression but without epilepsy. We observed a lack of inhibitory control of the HPA system in patients with epilepsy, also in the absence of enzyme inducing medication. An impact of the temporal lobe location of the epileptic focus could not be observed. Thus, epilepsies share with depression the deficiencies in the feedback mechanism of the HPA system, proposing common pathophysiological features of up to now unknown nature.

Interleukin-1beta Causes Fluoxetine Resistance in an Animal Model of Epilepsy-Associated Depression

“…Concrete mechanisms of epilepsy-associated depression remain by and large elusive, although some studies have implicated the dysregulation of the HPA axis [10], and the upregulation of presynaptic 5-HT1A receptors [11].…”

5-HT1A Receptor Binding in Temporal Lobe Epilepsy Patients With and Without Major Depression

“…Bidirectional temporal relationships of comorbid conditions suggest shared etiologic explanations (27). Both conditions are associated with common biological characteristics including reduced hippocampal volume (18), neuropathological changes in amygdale (1,10), and hypothalamic-pituitary-adrenal (HPA) axis dysfunction (21,53).…”

Ghrelin Regulation in Epilepsy

“…In fact, in these patients increased circulating levels of cortisol and adrenocorticotropic hormone (ACTH) are measured, relating to a deficient inhibitory feedback system after the suppression by dexamethasone (Zobel et al, 2004). These data have been confirmed by Galimberti and co-workers who reported decreased levels of dehydroepiandrosterone sulphate (DHEAS), in women with frequent seizures; this is not merely due to enzymeinducing antiepileptic drugs (Galimberti et al, 2005).…”

“…Increased basal cortisol levels, measured in salivary samples, have been recently described in patients with psychogenic nonepileptic seizures as independent of the acute occurrence of seizures; in addition, a basal hypercortisolism is present in patients with a trauma history, underling an involvement of psychological stress factors (Bakvis et al, 2010). However, further studies about the time of the onset of a blunted inhibitory control of hypothalamicpituitary-adrenocortical system, are important to understand if this discharge is only a secondary effect of seizures or whether it also determines a susceptibility to epilepsy (Zobel et al, 2004). At this regard, it is known that the hypercortisolism observed in several neuropsychiatric disorders is partially due to reduced neuronal outgrowth and plasticity with a lower hippocampus volume and cognitive deficits (McEwen et al, 1992;Sapolsky, 2000;Sapolsky et al, 1986;Sheline et al, 1996).…”