Homocysteine, but not MTHFR gene polymorphism, influences depressive symptoms in patients with schizophrenia.

Background: Methylenetetrahydrofolate reductase (MTHFR) is the key enzyme of folate metabolism in the process of one-carbon cycle and its deficiency results in elevated homocysteine concentration. In this study, we hypothesized that MTHFR C677T polymorphism and homocysteine concentration may play important roles in the development of depressive symptoms in schizophrenia.

Methods: We recruited 715 patients with stable schizophrenia, and among them, 197 schizophrenia patients under olanzapine monotherapy were enrolled for homocysteine concentration analysis. The Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS) were employed to evaluate psychiatric and depressive symptoms.

Results: When the 715 schizophrenia patients were evaluated by CDSS, 326 individuals (45.6%) had depressive symptoms. No significant differences were observed in C677T genotype and allele distributions between the schizophrenia with or without depression groups. Schizophrenia patients with depression have higher levels of homocysteine than those without depression (P = 0.019). There was a positive correlation between the homocysteine levels and CDSS score (r = 0.22, P = 0.002).

Conclusion: Our findings suggested that higher levels of homocysteine may be a risk factor for the development of depressive symptoms in schizophrenia patients.