Evidence from many different lines of research supports the hypothesis that schizophrenia is a disorder of development with etiological factors implicated as early as the second trimester in utero. We suggest that low maternal folate, acting to increase homocysteine levels, may provide a functional link between many of the identified prenatal risk factors and the hypothesized mechanisms whereby neurodevelopmental patterning deviates toward a schizophrenic potential.
PubMed was searched from the present back to 1963, when elevated homocysteine was identified as a pathogen in homocystinuria as first described by Carson and colleagues (Arch Dis Child 1963;38:425–36). All articles for homocystinuria, homocysteine, folate, and development with schizophrenia were evaluated.
The findings from this review support the hypothesis that maternal low folate and high homocysteine levels may provide a potential teratogenic mechanism that increases the risk for developing schizophrenia.
The potential role of maternal folate deficiency and hyperhomocystinemia in the genesis of schizophrenia would extend the range of their known teratogenic effects. Given the potential for preventive treatment offered by this hypothesis, we believe further investigation into this mechanism is warranted.
1From the Departments of Genetics and Psychiatrys, Harvard Medical School; McLean Hospital, Belmont, MA
2Children's Hospital Boston, Boston, MA
†Correspondence: Jonathan D. Picker, Fegan 10, Children's Hospital Boston, 300 Longwood Ave., Boston, MA, 02115. Email:email@example.com
Original manuscript received 27 September 2004, accepted for publication subject to revision 21 January 2005; revised manuscript received 17 February 2005.