HOMOZYGOUS THERMOLABILE METHYLENETETRAHYDROFOLATE REDUCTASE IN SCHIZOPHRENIA-LIKE PSYCHOSIS

The gene for methylenetetrahydrofolate reductase (MTHFR) has shown pol ymorphism in the general human population. In its homozygous form, a C 677T mutation occurs in more than 5% of the grown-up population and pr oduces a thermolabile variant which reduces the overall enzyme activit y to less than 30% of normal. We investigated patients with schizophre nia-like psychosis. If hyperhomocysteinemic, their DNA-genotype for th ermolabile C677T mutation was determined. Seven of 11 patients, six ma les and one female, were homozygous for thermolabile MTHFR. One male p atient was heterozygous and all three normal homozygotes were females. In the patients who were homozygous for the C677T mutation, the homoc ysteine concentrations did not respond to vitamin B12 but were normali zed by folate supplementation. In the normal homozygotes, however, the homocysteine concentrations were reduced by vitamin B12 alone. Our re sults suggest that homozygosity for thermolabile MTHFR is a risk facto r for schizophrenia-like psychosis. Possibly, this risk may be reduced by folate supplementation.