Contribution of methylenetetrahydrofolate reductase (MTHFR) polymorphisms to negative symptoms in schizophrenia
Contribution of methylenetetrahydrofolate reductase (MTHFR) polymorphisms to negative symptoms in schizophrenia
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DOI：
10.1016/j.biopsych.2006.12.017
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发表时间：
2008-01-01
影响因子：
10.6
通讯作者：
Goff, Donald C.
中科院分区：
文献类型：
--
作者：
Roffman, Joshua L.;Weiss, Anthony P.;Goff, Donald C.
背景：叶酸缺乏可能导致精神分裂症的阴性症状，但其潜在机制仍不确定。我们检查了亚甲基四氢叶酸还原酶 (MTHFR) C677T 和 A1298C 功能多态性是否会导致阴性症状。方法：使用阳性和阴性症状量表 (PANSS) 对门诊精神分裂症患者 (n = 200) 进行评估。受试者还提供了 MTHFR 基因型和血清化学分析的血液样本。根据基因型对 PANSS 症状、叶酸和同型半胱氨酸状态进行比较。结果：677T 等位基因负载与阴性症状严重程度相关。与我们的预期相反，T 等位基因还被发现可以预防阳性症状。 A1298C 多态性不会导致阴性症状，仅微弱地导致阳性症状。通过单倍型分析证实了C677T多态性的具体作用。在 667T 等位基因纯合的患者中，血清叶酸水平与阴性症状严重程度相关。结论：MTHFR 677T 等位基因负荷增加会增加精神分裂症阴性症状的风险，同时降低阳性症状的严重程度。此外，低血清叶酸与 677T 变体 MTHFR 的生化相互作用可能会诱导下游效应，从而导致阴性症状的表达。
Background: Folate deficiency may contribute to negative symptoms in schizophrenia, but the underlying mechanism remains uncertain. We examined whether the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C functional polymorphisms contribute to negative symptoms.Methods: Outpatients with schizophrenia (n = 200) were evaluated with the Positive and Negative Syndrome Scale (PANSS). Subjects also provided a blood sample for MTHFR genotype and serum chemistries. Comparisons of PANSS symptoms, folate, and homocysteine status were conducted based on genotype.Results: The 677T allele load was associated with negative symptom severity. Contrary to our expectations, the T allele was also found to be protective against positive symptoms. The A1298C polymorphism did not contribute to negative symptoms, and only weakly to positive symptoms. The specific effects of the C677T polymorphism were confirmed with haplotype analysis. Among patients homozygous for the 667T allele, serum folate levels correlated with negative symptom severity.Conclusions: Increased MTHFR 677T allele load confers risk for negative symptoms in schizophrenia, while reducing severity of positive symptoms. Further, the biochemical interaction of low serum folate with 677T-variant MTHFR may induce downstream effects salient to the expression of negative symptoms.