Folate, homocysteine, interleukin-6, and tumor necrosis factor alfa levels, but not the methylenetetrahydrofolate reductase C677T polymorphism, are risk factors for schizophrenia.

The methylenetetrahydrofolate reductase (MTHFR) C677T mutation has been associated to high homocysteine levels and schizophrenia. Since cytokines are altered in schizophrenia and increments of homocysteine could promote an inflammatory response, it was investigated whether interleukin-6 (IL-6) and tumor necrosis factor alfa (TNFalpha) levels are modulated by the MTHFR genotype. Serum levels of TNFalpha, IL-6, B(12), homocysteine, folate and red blood cell (RBC) folate as well as the MTHFR genotype were determined in a group of schizophrenic patients and compared to those of a control group. RBC folate levels were reduced and homocysteine and the two cytokines' concentrations were elevated in all patients as compared to controls. RBC folate in both heterozygous (CT) and homozygous (TT) patients was significantly different to that of their respective control groups. Homocysteine levels found in patients were significantly higher than those found in controls, only in individuals carrying the TT genotype. Cytokine levels were augmented in the group of patients irrespective of the genotype, and significant differences were found in all cases, except for TNFalpha levels in those subjects carrying the CC genotype. After adjusting for sex, low levels of RBC folate, high levels of homocysteine, both medium and high levels of TNFalpha and high IL-6 levels were associated with schizophrenia. MTHFR genotype was not a risk factor for developing the disease, although a larger sample is required to confirm this finding.