Objective:To compare the serum levels of neuropeptide and cytokines in first episode depressive patients before and after citalopram treatment. Methods:The serum levels of neuropeptide[neuropeptide Y (NPY),β-endorphin (β-EP) and Motilin (MTL)]and cytokines[tumor necrosis factor α(TNF-α) and insulin-like growth factorsⅡ(IGF-Ⅱ)] were measured using radioimmunoassay in 50 first-episode drug-naive depressive patients before and after antidepressant treatment and 40 healthy controls. Severity of depression and treatment efficacy were assessed according to the Hamilton Depression Scale (HAMD-17) and Hamilton Anxiety Scale (HAMA),and analyzed with the SPSS17.0 statistical package. Results:The serum levels of β-EP (340.31 ± 94.97 pg/ml),TNF-α(14.64 ± 9.23 ng/ml) and IGF-II (0.80 ± 0.30 ng/ml) were significantly higher in first-episode drug-naive depression patients than controls (all P < 0.0001),and serum levels of NPY (96.41 ± 32.98 pg/ml) in depressive patients were significantly lower than control group (P < 0.0001). The serum levels of IGF-II reduced (P < 0.0001) after 6-week of therapy,while NPY increased (P < 0.05). Regression analysis showed that the serum NPY was the important risk factor of depressive (P = 0.012),and the change of MTL was the association factor influencing the therapeutic effect (P = 0.016). Conclusion:The change of serum neuropeptide and cytokines may be involved in pathophysiology of the first episode depressive patients. The low serum NPY may be a potential predictive index for the depressive episode,while the increase of MTL can predict the antidepressant efficacy.