The findings of this study were as follows: (1) serum irisin levels in patients with depression were lower compared with those in patients without depression; (2) reduced serum levels of irisin were powerful biological markers of risk of developing PSD even after adjustment by variables, and thus, it may be used as a future therapeutic target in patients with ischemic stroke; and (3) irisin showed a significantly greater discriminatory ability to predict PSD as compared with other biomarkers, such as Hs-CRP, HCY, age, and serotonin. This evidence concerns the gene FNDC5 and major depressive disorder.