Schizophrenia Program, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Psychiatry, Jinhua Second Hospital, Jinhua, Zhejiang, China.
Psychoneuroendocrinology. 2018 Mar;89:1-6. doi: 10.1016/j.psyneuen.2017.12.024. Epub 2017 Dec 29.
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.
我们最近的研究报告称，肿瘤坏死因子-α（TNF-α）与精神分裂症患者的脑源性神经营养因子（BDNF）呈负相关。先前的研究表明，TNF-α可以调节 BDNF 的细胞外分泌。因此，我们假设 TNF-α基因（TNF-α）可能与 BDNF 基因（BDNF）相互作用，从而影响精神分裂症的风险。
我们从中国东部的三家精神病院招募了 694 名精神分裂症患者和 725 名健康对照者。采用阳性和阴性症状量表（PANSS）评估症状严重程度，采用重复性成套神经心理状态测验（RBANS）评估认知功能。检测 BDNF 基因 rs6265 和 TNF-α 基因 rs1799964 的 SNP。
病例组和对照组在 rs6265 或 rs1799964 中，等位基因和基因型频率均无显著差异。rs6265AA+AG×rs1799964CC+CT 与精神分裂症显著相关（OR=1.14，95%CI：1.02-1.27；P=0.02）。携带 rs6265A 和 rs1799964C 等位基因的患者的 RBANS 注意力和总分与不携带这两种等位基因的患者存在显著差异（P=0.03 和 P=0.03，分别在 Bonferroni 校正后）。
我们的研究结果初步提供了证据，表明 BDNF 和 TNF-α 的相互作用可能导致精神分裂症和认知功能障碍的易感性。
