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High Maternal Homocysteine Tied to Schizophrenia

By David Douglas

NEW YORK (Reuters Health) Jan 12 - Elevated third-trimester levels of homocysteine appear to be associated with an increased risk of offspring subsequently developing schizophrenia, researchers report in the January issue of the Archives of General Psychiatry.

Dr. Alan S. Brown told Reuters Health, "Our finding could have important implications for our understanding of causes of schizophrenia that affect the development of the brain in the prenatal period."

Elevated levels of homocysteine are associated with abnormal placental function and pregnancy complications, note Dr. Brown of Columbia University, New York and colleagues there and at the Kaiser Foundation Division of Research, Oakland, and the Public Health Institute, Berkeley, in California.

To investigate whether elevated maternal levels of homocysteine during the third trimester were also associated with adult schizophrenia risk in offspring, the researchers conducted a nested case-control study of a birth cohort with more than 12,000 members born from 1959 through 1967 and followed up for schizophrenia from 1981 through 1997.

In all, 63 were diagnosed with schizophrenia and other spectrum disorders. The 122 controls were matched members of the birth cohort without such a diagnosis.

In a model that tested for a threshold effect of third-trimester homocysteine levels, the researchers found that an elevated homocysteine level was associated with a significant increase in the risk of schizophrenia (odds ratio, 2.39).

The team suggests that homocysteine may have effects on brain structure and function or lead to subtle damage to the placental vasculature that compromises oxygen delivery to the fetus.

Should a causal link be confirmed, Dr. Brown concluded, "it has the potential to lead to prevention of cases of schizophrenia through relatively simple measures such as folic acid supplementation in the later part of pregnancy."

Arch Gen Psychiatry 2007;64:31-39.
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