Background: Antidepressants have variable efficacies in subjects with major depressive disorder (MDD). Nerve growth factor (NU.) has been suggested to play an important role in the pathogenesis of depressive symptoms and the response to antidepressant therapy. The aim of this study was to examine whether NGF gene polymorphisms are associated with the antidepressant therapeutic efficacy in subjects with MDD.Methods: A naturalistic follow-up study was carried out on 557 subjects with MDD. Of the enrolled patients, 304 completed the 8-week open-label antidepressant treatment. Seven single-nucleotide polymorphisms (SNPs) of the NGF gene were genotyped. The 21-item Hamilton Depression Rating Scale was used to assess depressive severity from baseline to endpoint. Tridimensional Personality Questionnaire was used to assess baseline personality traits. Single marker and haplotype analyses were conducted. Binary logistic regression was used to calculate odds ratios of remission. Structural equation modeling was used to analyze the predicted mediation effect.Results: A significant difference in genotype frequencies between remitters and non-remitters was observed in three NGF SNPs (rs12760036, rs7523654, and rs17033692). The haplotype analysis revealed that the CCC haplotype (rs2254527-rs6678788-rs12760036) was associated with a higher remission rate, while the CCA haplotype was associated with a lower remission rate. The harm avoidance psychological factor partially mediated the effect of NGF variants on antidepressant efficacy. Limitations: The selected SNPs may not cover whole NGF gene.Conclusions: NGF variants are associated with remission rates after 8-week antidepressant treatment, and harm avoidance partially mediated the effect of NGF variants on treatment outcomes. (C) 2015 Elsevier B.V. All rights reserved