Circulating nerve growth factor as a neuroimmune biomarker in first-episode major depressive disorder: Integrative analysis of serum levels and NGF Ala273Val (rs6330) polymorphism

Abstract

Background: Major depressive disorder (MDD) has been increasingly recognized as a systemic disorder involving neuroimmune and biochemical dysregulation. Circulating neurotrophic factors, particularly nerve growth factor (NGF), may serve as potential laboratory biomarkers reflecting neurobiological alterations. Methods: This case–control study enrolled 47 drug-naïve patients with first-episode MDD and 40 age- and sexmatched healthy controls. Serum NGF concentrations were quantified using enzyme-linked immunosorbent assay (ELISA). The NGF Ala273Val (rs6330) polymorphism was genotyped via polymerase chain reaction and direct sequencing. Statistical analyses included group comparisons, correlation analysis, and genotype–phenotype association evaluation. Results: Serum NGF levels were significantly elevated in patients with MDD compared with controls (36.81 ± 7.11 vs. 29.74 ± 5.69 pg/mL, P < 0.001). However, no significant correlation was observed between NGF concentrations and HAMD-17 scores (r = 0.12, P = 0.42). Genotype and allele distributions of the NGF Ala273Val polymorphism did not differ significantly between groups (P > 0.05), and no genotype-dependent differences in serum NGF levels were detected. Conclusion: Circulating NGF is significantly altered in first-episode MDD, supporting its role as a neuroimmunerelated biochemical marker associated with disease presence rather than symptom severity. The NGF Ala273Val polymorphism does not appear to influence susceptibility or peripheral NGF expression. These findings highlight the potential utility of serum NGF as a laboratory biomarker in the biochemical characterization of MDD.