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.

Our previous studies showed that in patients with brain diseases, neurotrophic factors in lacrimal fluid (LF) may change more prominently than in blood serum (BS). Since glial cell line-derived neurotrophic factor (GDNF) is involved in the control of neuronal networks in an epileptic brain, we aimed to assess the GDNF levels in LF and BS as well as the BDNF and the hypothalamic-pituitary-adrenocortical and inflammation indices in BS of patients with focal epilepsy (FE) and epilepsy and comorbid depression (FE + MDD) and to compare them with those of patients with major depressive disorder (MDD) and healthy controls (HC). GDNF levels in BS were similar in patients and HC and higher in FE taking valproates. GDNF levels in LF were significantly lower in all patient groups compared to controls, and independent of drugs used. GDNF concentrations in LF and BS positively correlated in HC, but not in patient groups. BDNF level was lower in BS of patients compared with HC and higher in FE + MDD taking valproates. A reduction in the GDNF level in LF might be an important biomarker of FE. Logistic regression models demonstrated that the probability of FE can be evaluated using GDNF in LF and BDNF in BS; that of MDD using GDNF in LF and cortisol and TNF-α in BS; and that of epilepsy with MDD using GDNF in LF and TNF-α and BDNF in BS.

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

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.

Brain-derived neurotrophic factor in blood serum and lacrimal fluid of patients with focal epilepsy.

OBJECTIVE: To evaluate brain-derived neurotrophic factor (BDNF) level in blood serum (BS) and lacrimal fluid (LF) of people with epilepsy (PWE). METHODS: It was a case-control study of 72 consecutive patients with focal epilepsy (cases, Epilepsy group) and 60 age- and gender-matched healthy volunteers (controls). Based on comorbid depression, two subgroups of PWE were formed. BDNF level was measured by enzyme-linked immunosorbent assay (ELISA) in BS and LF. RESULTS: Compared to controls, BDNF level (pg/mL) in PWE was lower both in BS (22,520 ± 3810 vs. 26,360 ± 3090, P < 0.000) and in LF (100.8 ± 23.3 vs. 113.4 ± 19.3, P = 0.001). However, no significant correlation was found between BDNF level in BS and LF either in the Epilepsy group or in controls. No impact of comorbid depression on BDNF level was found either in BS or LF of PWE. We revealed a higher BDNF level in LF of men as compared to women in controls and a similar non-significant trend in PWE. Higher BDNF level in BS of PWE receiving valproates versus other AEDs was found, however, a relatively small number of observations and use of polytherapy in most cases should be taken into account. SIGNIFICANCE: In patients with focal epilepsy, BDNF level is decreased both in BS and LF, though with no correlation between them. No association of BDNF levels with age and epilepsy characteristics, as well as the occurrence of depression, was found. Low BDNF level in LF could be considered as a non-invasive biomarker of focal epilepsy.