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Objective: Brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4) are neuro-trophins and they are critical regulators of the survival, differentiation, growth and plasticity of neuronal networks. There is plenty of evidence suggesting the involvement of altered levels of expression of neurotrophic factors in the pathophysiology of neuropsychiatric disorders. However, the relationship between neurotrophins and major depression (MD) remains unclear. In this study, we assessed the relationship between the BDNF, NT-3, NT-4 gene expression levels in blood cells and MD. Methods: In a case-control study, total RNA was obtained from blood cells, 51 MD patients (diagnosed according to the DSM-5 criteria) and 75 healthy controls. Detected with quantitative Real Time PCR, expression levels of BDNF, NT-3, NT-4 genes were compared between the groups. Results: In this study, BDNF expression levels of the patients with MD were significantly higher than the control group but no statistically significant difference between NT-3 and NT-4 expression levels. There was no differences in expression levels of BDNF, NT-3 and NT-4 genes in MD patients with family history. There was no statistically significant difference in the BDNF, NTF-3 and NTF-4 expression levels among the sex groups for the patient group and no statistically significant difference between MD patients according to antidepressant usage time. Discussion: Not only in understanding the pathogenesis of MD but also in the follow-up of treatment, expression level changes of BDNF gene in blood cells of MD patients must be considered because of the bidirectional movement of BDNF between the periphery and the brain and effect of changing serum BDNF levels. [Anadolu Psikiyatri Derg 2019; 20(6.000): 581-588]