In this study, we revealed the significant differences in serum BDNF, GDNF, 5-HT, and IL-1β among the HC, PWE, and PWECD groups, along with the negative correlation with depression severity in serum GDNF and 5-HT levels, supporting their role in epilepsy and comorbid depression. This evidence concerns the gene BDNF and depressive symptom measurement.