Effect of the MTHFR C677T Polymorphism on Antipsychotic Drug Dosage and Treatment Response of Psychotic Patients in a Naturalistic Setting

Abstract

The T allele of the methylene tetrahydrofolate reductase (MTHFR) C667T polymorphism (rs1801133) encodes an enzyme with decreased activity, increased folic acid requirements and elevated plasma homocysteine concentration. The same allele has been associated in the past with lower age of onset of schizophrenia and better response to antipsychotic treatment in patients of northern European descent. In this study, we have examined the association of MTHFR C667T with the age of onset, dose requirements and response to treatment in a group of Greek patients suffering from schizophrenia and other psychotic disorders. One hundred and four patients were recruited from the 2nd Department of Psychiatry of the Psychiatric Hospital of Thessaloniki, from July 2014 until October 2015, of which 96 were successfully genotyped for the polymorphism with a PCR-RFLP method. Response to antipsychotic treatment involving typical and atypical antipsychotics, with doses converted to chorpromazine equivalents (CPZeqs), was estimated by a follow-up assessment with PANSS after 4 weeks of treatment. In patients suffering from psychotic disorders other than schizophrenia the T allele of rs1801133 was significantly associated (P = 0.034) with better response to antipsychotic medication. Also, carriers of the T allele tended to receive lower drug doses than non-carriers (P = 0.069). These associations were independent of the effect of CYP2D6 genotype. No associations were detected in the subgroup of patients with diagnosis of schizophrenia. The polymorphism was not associated with age of onset in either subgroup. The MTHFR C667T polymorphism appears to affect response to treatment and antipsychotic dosage requirements but its effect is modulated by diagnosis and, presumably, the strength of the intervention.