TNF-α in schizophrenia: Associations with cholesterol and genetic variations

Tumor necrosis factor-α (TNF-α), a pro-inflammatory factor is involved in the pathophysiology of schizophrenia. The roles of antipsychotics, cholesterol, and TNFA single nucleotide polymorphisms (SNPs) on elevation of TNF-α in schizophrenia have been inadequately evaluated. Therefore, the present study aimed to compare serum TNF-α level between Malaysian patients with schizophrenia and healthy controls, as well as to investigate the effects of antipsychotics, cholesterol, and TNFA SNPs (rs361525, rs1800629, and rs1800630) on serum TNF-α level in schizophrenia. This study involved 150 medicated outpatients with schizophrenia and 139 healthy controls. Their blood was collected and processed into serum. Serum TNF-α, high-density lipoprotein cholesterol (HDLC), and low-density lipoprotein cholesterol (LDL-C) levels were measured. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to genotype TNFA SNPs. After covariate adjustment, our findings demonstrated significantly increased serum TNF-α and HDL-C levels in patients, and there was a significant association between serum LDL-C and TNF-α levels in this group. Meanwhile, there was no significant association between antipsychotics and serum TNF-α levels. This could be due to the overlapping pro- or anti-inflammatory effects of each antipsychotic as some of the patients were not on monotherapy. However, TNFA rs361525 polymorphism significantly modified the association between schizophrenia and serum TNF-α level. In conclusion, this study suggested that the elevated level of TNF-α in schizophrenia may be influenced by cholesterol and TNFA polymorphisms.