Interaction between BDNF and TNF-α genes in schizophrenia

Our recent work reported that tumor necrosis factor-α (TNF-α) is negatively correlated with brain-derived neurotrophic factor (BDNF) in patients with schizophrenia. A previous study has shown that TNF-α could regulate the extracellular secretion of BDNF. Therefore, we hypothesized that the TNF-α gene (TNF-α) may interact with the BDNF gene (BDNF) to influence schizophrenia risk. We recruited 694 patients with schizophrenia from three mental hospitals in Eastern China and 725 healthy controls. The Positive and Negative Syndrome Scale (PANSS) was employed to evaluate symptom severity. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to assess cognitive function. The SNPs rs6265 in BDNF and rs1799964 in TNF-α were genotyped. There were no significant differences in allele and genotype frequencies in either rs6265 or rs1799964 between the case and control groups. A significant association of rs6265 AA + AG × rs1799964 CC + CT with schizophrenia was observed (OR = 1.14, 95%CI: 1.02-1.27; P = .02). There were significant differences in the RBANS attention and total scores between the patients with rs6265A and rs1799964C alleles and those without these two alleles (P = .03 and P = .03 after Bonferroni correction, respectively). Our findings provided preliminary evidence that the interaction of BDNF and TNF-α may confer susceptibility to schizophrenia and cognitive dysfunction.