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Evidence suggests that brain-derived neurotrophic factor (BDNF) and glial cell line -derived neurotrophic factor (GDNF) are important in the regulation of synaptic plasticity, which plays a key role in the cognitive processes in psychiatric disorders. Our work aimed at exploring the associations between serum BDNF and GDNF levels and cognitive functions in first-episode drug-naïve (FEDN) patients with schizophrenia.The BDNF and GDNF levels of 58 FEDN patients and 55 age- and sex-matched healthy controls were measured and test subjects were examined using several neurocognitive tests including the verbal fluency test (VFT), the trail making test (TMT), the digit span test (DST), and the Stroop test.Patients performed significantly worse than controls in nearly all neurocognitive performances except the forward subscale part of the DST. BDNF levels were inversely correlated to TMT-part B scores and positively correlated to VFT-action in the FEDN group. GDNF levels showed a positive correlation with VFT-action scores and a negative correlation with TMT-part B scores of these patients.Current data suggests that cognitive dysfunction widely exists in the early stages of schizophrenia. BDNF and GDNF may be jointly contributed to the pathological mechanisms involved in cognitive impairment in FEDN patients with schizophrenia.First-episode drug-naïve schizophrenia patients performed significantly worse than controls on nearly all cognitive tests.Serum concentrations of BDNF and GDNF were markedly lower in these patients compared to heatlhy controls.For the patients only, BDNF and GDNF were both related to cognitive function.