title: Elevated prenatal homocysteine levels as a risk factor for schizophrenia.
abstract: 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.
authors.affiliation: 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
authors.forename: Alan S
authors.initials: AS
authors.lastname: Brown
authors.forename: Teodoro
authors.initials: T
authors.lastname: Bottiglieri
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Schaefer
authors.forename: Charles P
authors.initials: CP
authors.lastname: Quesenberry
authors.forename: Liyan
authors.initials: L
authors.lastname: Liu
authors.forename: Michaeline
authors.initials: M
authors.lastname: Bresnahan
authors.forename: Ezra S
authors.initials: ES
authors.lastname: Susser
mesh_terms: 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
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D006710:Homocysteine