Document Detail

Elevated prenatal homocysteine levels as a risk factor for schizophrenia.
MedLine Citation:
PMID:  17199052     Owner:  NLM     Status:  MEDLINE    
CONTEXT: 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.
DESIGN: Nested case-control study of a large birth cohort, born from 1959 through 1967 and followed up for schizophrenia from 1981 through 1997.
SETTING: Population-based birth cohort and health plan.
PARTICIPANTS: 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.
MAIN MEASURES: 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.
Alan S Brown; Teodoro Bottiglieri; Catherine A Schaefer; Charles P Quesenberry; Liyan Liu; Michaeline Bresnahan; Ezra S Susser
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Archives of general psychiatry     Volume:  64     ISSN:  0003-990X     ISO Abbreviation:  Arch. Gen. Psychiatry     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2007-01-02     Completed Date:  2007-02-28     Revised Date:  2012-05-11    
Medline Journal Info:
Nlm Unique ID:  0372435     Medline TA:  Arch Gen Psychiatry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  31-9     Citation Subset:  AIM; IM    
College of Physicians and Surgeons of Columbia University and New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, USA.
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MeSH Terms
Case-Control Studies
Child of Impaired Parents / statistics & numerical data
Cohort Studies
Homocysteine / blood*,  metabolism,  physiology
Maternal-Fetal Exchange / physiology
Pregnancy Trimester, Third / blood
Prenatal Exposure Delayed Effects*
Psychotic Disorders / epidemiology,  etiology,  metabolism
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors,  blood
Risk Factors
Schizophrenia / epidemiology*,  etiology,  metabolism
Grant Support
1K02 MH 65422-01/MH/NIMH NIH HHS; 1R01 MH 63264-01A1/MH/NIMH NIH HHS; K02 MH065422/MH/NIMH NIH HHS; N01 HD 13334/HD/NICHD NIH HHS; N01 HD 63258/HD/NICHD NIH HHS
Reg. No./Substance:
0/Receptors, N-Methyl-D-Aspartate; 454-28-4/Homocysteine
Comment In:
Arch Gen Psychiatry. 2007 Aug;64(8):980-1   [PMID:  17679645 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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