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

Abstract

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.

Keywords: blood serum; brain-derived neurotrophic factor; cortisol; focal epilepsy; glial cell line-derived neurotrophic factor; hypothalamic–pituitary–adrenocortical axis; lacrimal fluid; major depressive disorder; tumor necrosis factor-α.

Figure 1

Neurotrophic factors in biological fluids (lacrimal fluid and blood serum) of patients with focal epilepsy (FE), epilepsy and comorbid depression (FE + MDD), and major depressive disorder (MDD) and of healthy controls (HC): GDNF in blood serum (a); GDNF in lacrimal fluid (b); and BDNF in blood serum (c). Kruskal–Wallis test (with post hoc Dunn’s test) for GDNF in BS and GDNF in LF as well as one-way ANOVA (with post hoc Tukey test) for BDNF were used to compare multiple unrelated groups. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.

Figure 2

Cortisol (a) and TNF-α (b) in blood serum of patients with focal epilepsy (FE), epilepsy and comorbid depression (FE + MDD), and major depressive disorder (MDD) and of healthy controls (HC). For the comparisons of unrelated groups, Kruskal–Wallis test adjusted for multiple comparisons and post hoc Dunn’s test were used. ** p < 0.01, **** p < 0.0001.

Figure 3

Dependence of changes in GDNF in LF (a) and BDNF (b) levels on the likelihood of developing epilepsy. Vertical lines along the x-axis indicate observations; gray bar along the blue line indicates a 95% confidence interval.

Figure 4

Dependence of changes in GDNF in LF (a), cortisol (b) and TNF-α (c) levels on the likelihood of developing depression. Vertical lines along the x-axis indicate observations; gray bar along the blue line indicates a 95% confidence interval.

Figure 5

Dependence of changes in GDNF in LF (a), TNF-α (b), and BDNF (c) levels on the likelihood of developing comorbid depression and epilepsy. Vertical lines along the x-axis indicate observations; a gray bar along the blue line indicates a 95% confidence interval.