Elevated Serum Cortisol Levels in Patients with Focal Epilepsy, Depression, and Comorbid Epilepsy and Depression

Abstract

Background: The hypothalamic-pituitary-adrenal (HPA) axis, inflammatory processes and neurotrophic factor systems are involved in pathogenesis of both epilepsy and depressive disorders. The study aimed to explore these systems in patients with focal epilepsy (PWE, n = 76), epilepsy and comorbid depression (PWCED n = 48), and major depressive disorder (PWMDD, n = 62) compared with healthy controls (HC, n = 78). Methods: Parameters of the HPA axis, neurotrophic factors, and TNF-α were measured in blood serum along with the hemogram. Results: Serum cortisol level was augmented in PWE, PWCED, and PWMDD compared with HC and was higher in PWMDD than in PWE. Serum cortisol negatively correlated with Mini–Mental State Examination (MMSE) score in PWE, and positively with depression inventory–II (BDI-II) score in PWMDD. Only PWMDD demonstrated elevated plasma ACTH. Serum TNF-α, lymphocytes, and eosinophils were augmented in PWMDD; monocytes elevated in PWE and PWCED, while neutrophils were reduced in PWE and PWMDD. Serum BDNF was decreased in PWE and PWCED, CNTF was elevated in all groups of patients. In PWE, none of above indices depended on epilepsy etiology. Conclusions: The results confirm the involvement of HPA axis and inflammatory processes in pathogenesis of epilepsy and depression and provide new insights in mechanisms of epilepsy and depression comorbidity.

Reduced Levels of Lacrimal Glial Cell Line-Derived Neurotrophic Factor (GDNF) in Patients with Focal Epilepsy and Focal Epilepsy with Comorbid Depression: A Biomarker Candidate

“…In the present study, serum BDNF was reduced in all groups of patients compared with HC. Overall, these data confirm the results of other studies that suggest an involvement of BDNF in the pathogenesis of epilepsy [6] and depression [27] and those of our previous study [28].…”

“…When such groups of patients were compared in the present study, the cortisol level in the serum of the MDD group was insignificantly higher than that in FE, though showing a statistically significant trend (p < 0.09). However, similar to the previous data, the changes in levels of GDNF in LF and BDNF and cortisol in BS, assessed in the present study, did not depend on the etiology of epilepsy and were related to epilepsy in general, independent of its etiology [28].…”

“…Taking into consideration that epilepsy may be regarded as a model of chronic stress [4], the lack of pronounced cortisol activation in FE may be due to the deeper exhaustion of HPA axis in some patients with epilepsy. In our previous study, it was shown that, in MDD, serum GDNF and cortisol concentrations were significantly higher than those in FE [28]. When such groups of patients were compared in the present study, the cortisol level in the serum of the MDD group was insignificantly higher than that in FE, though showing a statistically significant trend (p < 0.09).…”

The Role of the Adrenal–Gut–Brain Axis on Comorbid Depressive Disorder Development in Diabetes

“…In fact, around 50% of depressed patients and 80% of severely depressed patients showed hyperactivity of the HPA axis [79,80]. In addition, depressive patients presented adrenal hypertrophy and an increase in the circulating levels of both ACTH and cortisol [81][82][83][84]. Furthermore, repeated exposure to short-term stress or injection of glucocorticoids induced depressive-like behavior in mice [85].…”

Molecular and Cellular Mechanisms of Epilepsy

“…As one of the hypotheses, the authors of the study propose that epilepsy is a model of chronic stress for human beings. This hypothesis is supported by the fact that patients with focal epilepsy have higher levels of cortisol in their blood serum than healthy people [2]. In addition, patients with epilepsy have a high incidence of comorbid depressive disorders, one of the causes of which is stress.…”