Elevated prenatal homocysteine levels as a risk factor for schizophrenia.
BACKGROUND
Elevated prenatal homocysteine level is a plausible risk factor for schizophrenia because of its partial antagonism of N-methyl-D-aspartate receptors under physiologic glycine concentrations and its association with abnormal placental function and pregnancy complications.


OBJECTIVE
We examined whether elevated maternal levels of homocysteine during the third trimester were associated with adult schizophrenia risk.


METHODS
Nested case-control study of a large birth cohort, born from 1959 through 1967 and followed up for schizophrenia from 1981 through 1997.


METHODS
Population-based birth cohort and health plan.


METHODS
Cases (n = 63) were diagnosed with schizophrenia and other spectrum disorders (mostly schizophrenia and schizoaffective disorder). Controls (n = 122) belonged to the birth cohort; had not been diagnosed with a schizophrenia spectrum or major affective disorder; and were matched to cases on date of birth, sex, length of time in the cohort, and availability of maternal serum samples.


METHODS
Archived maternal serum samples were assayed for homocysteine levels during pregnancies of cases and matched controls.


RESULTS
In a model that tested for a threshold effect of third-trimester homocysteine levels, an elevated homocysteine level was associated with a greater than 2-fold statistically significant increase in schizophrenia risk (odds ratio, 2.39; 95% confidence interval, 1.18-4.81; P = .02).


CONCLUSIONS
These findings indicate that elevated third-trimester homocysteine levels may be a risk factor for schizophrenia. Elevated third-trimester homocysteine levels may elevate schizophrenia risk through developmental effects on brain structure and function and/or through subtle damage to the placental vasculature that compromises oxygen delivery to the fetus. If future studies both replicate this association and support a causal link, then the use of folic acid supplementation would merit evaluation as a strategy for prevention of schizophrenia in offspring.
Brown
Alan S
AS
College of Physicians and Surgeons of Columbia University and New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, USA. asb11@columbia.edu
Bottiglieri
Teodoro
T
Schaefer
Catherine A
CA
Quesenberry
Charles P
CP
Liu
Liyan
L
Bresnahan
Michaeline
M
Susser
Ezra S
ES
D000328:Adult; D016022:Case-Control Studies; D002648:Child; D016241:Child of Impaired Parents / Q000706:statistics & numerical data; D015331:Cohort Studies; D005260:Female; D006710:Homocysteine / Q000097:blood* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008431:Maternal-Fetal Exchange / Q000502:physiology; D011247:Pregnancy; D011263:Pregnancy Trimester, Third / Q000097:blood; D011297:Prenatal Exposure Delayed Effects; D011618:Psychotic Disorders / Q000453:epidemiology / Q000209:etiology / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000097:blood; D012307:Risk Factors; D012559:Schizophrenia / Q000453:epidemiology* / Q000209:etiology / Q000378:metabolism
D016194:Receptors, N-Methyl-D-Aspartate; D006710:Homocysteine