Brown Alan S, Bottiglieri Teodoro, Schaefer Catherine A, Quesenberry Charles P, Liu Liyan, Bresnahan Michaeline, Susser Ezra S
College of Physicians and Surgeons of Columbia University and New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, USA.
Arch Gen Psychiatry. 2007 Jan;64(1):31-9. doi: 10.1001/archpsyc.64.1.31.
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.
We examined whether elevated maternal levels of homocysteine during the third trimester were associated with adult schizophrenia risk.
Nested case-control study of a large birth cohort, born from 1959 through 1967 and followed up for schizophrenia from 1981 through 1997.
Population-based birth cohort and health plan.
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.
Archived maternal serum samples were assayed for homocysteine levels during pregnancies of cases and matched controls.
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).
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.
孕期同型半胱氨酸水平升高可能是精神分裂症的一个风险因素，因为在生理甘氨酸浓度下它对N-甲基-D-天冬氨酸受体具有部分拮抗作用，且与胎盘功能异常及妊娠并发症相关。
我们研究了孕晚期母体同型半胱氨酸水平升高是否与成人精神分裂症风险相关。
对1959年至1967年出生的大型出生队列进行巢式病例对照研究，并于1981年至1997年对精神分裂症进行随访。
基于人群的出生队列和健康计划。
病例组（n = 63）被诊断为精神分裂症及其他谱系障碍（大多为精神分裂症和分裂情感性障碍）。对照组（n = 122）来自该出生队列；未被诊断患有精神分裂症谱系或重度情感障碍；并根据出生日期、性别、队列中的时间长度以及母体血清样本的可用性与病例组匹配。
对病例组和匹配对照组孕期的存档母体血清样本进行同型半胱氨酸水平检测。
在一个测试孕晚期同型半胱氨酸水平阈值效应的模型中，同型半胱氨酸水平升高与精神分裂症风险在统计学上显著增加2倍以上相关（优势比，2.39；95%置信区间，1.18 - 4.81；P = .02）。
这些发现表明，孕晚期同型半胱氨酸水平升高可能是精神分裂症的一个风险因素。孕晚期同型半胱氨酸水平升高可能通过对脑结构和功能的发育影响和/或通过对胎盘血管系统的细微损害，从而损害向胎儿的氧气输送，进而增加精神分裂症风险。如果未来的研究既重复了这种关联又支持因果联系，那么补充叶酸作为预防后代精神分裂症的一种策略将值得评估。
