Do maternal folate and homocysteine levels play a role in neurodevelopmental processes that increase risk for schizophrenia?
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Picker
Jonathan D
JD
Department of Genetics, Harvard Medical School; McLean Hospital, Belmont, MA, USA. jonathan.picker@childrens.harvard.edu
Coyle
Joseph T
JT
D001921:Brain / Q000196:embryology / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005315:Fetal Diseases / Q000453:epidemiology / Q000209:etiology* / Q000503:physiopathology*; D005492:Folic Acid / Q000097:blood*; D006710:Homocysteine / Q000097:blood*; D006712:Homocystinuria / Q000453:epidemiology; D006801:Humans; D020138:Hyperhomocysteinemia / Q000453:epidemiology / Q000235:genetics; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D009035:Mothers; D011247:Pregnancy; D011263:Pregnancy Trimester, Third / Q000502:physiology; D011295:Prenatal Care; D012307:Risk Factors; D012559:Schizophrenia / Q000453:epidemiology / Q000503:physiopathology* / Q000517:prevention & control
D006710:Homocysteine; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)