School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Am J Geriatr Psychiatry. 2009 Oct;17(10):847-55. doi: 10.1097/JGP.0b013e3181aad5b2.
The 5,10-methylenetetrahydrofolate reductase gene (MTHFR) has been linked to unipolar major depressive disorder (MDD) and magnetic resonance imaging (MRI) hyperintensities. The authors examined the relationship between the MTHFR C677T polymorphism (C677T) and a) geriatric depression, b) MRI hyperintense lesion volume, and c) neurocognitive test performance.
Cross-sectional.
Duke University Medical Center.
Depressed (N = 178) and comparison (N = 85) elderly subjects.
Subjects had blood drawn to assess MTHFR genotype, were imaged by MRI to determine their white matter hyperintense lesion (WML) and gray matter hyperintense lesion (GML) volume, and assessed using a comprehensive neurocognitive battery evaluating multiple domains of function. Linear regression models were fit to test the effect of genotype, a depression by genotype interaction, and an age by genotype interaction on both hyperintense lesion volume measures and neurocognitive task performance.
The MTHFR C677T genotype by age interaction term was significantly associated with MRI WML volume (p = 0.0175); however, this relationship was no longer statistically significant when WML volumes underwent a log transformation to produce a more normal distribution. The 677T allele was neither more frequent in depressed subjects nor associated with either gray matter hyperintensity volume or neurocognitive test performance.
MTHFR genotype affects the relationship between age and WML volume where individuals who carry the 677T allele exhibit greater WML volume by age, although this relationship should be verified given the failure to replicate the finding using transformed WML volumes. Genotype was not related to GML volume, cognitive function, or presence of depression, although demographic differences could account for this negative finding.
5,10-亚甲基四氢叶酸还原酶基因（MTHFR）与单相重性抑郁障碍（MDD）和磁共振成像（MRI）高信号有关。作者研究了 MTHFR C677T 多态性（C677T）与 a）老年抑郁症、b）MRI 高信号病变体积和 c）神经认知测试表现之间的关系。
横断面研究。
杜克大学医学中心。
抑郁组（N=178）和对照组（N=85）老年受试者。
抽取受试者血液以评估 MTHFR 基因型，通过 MRI 成像确定其白质高信号病变（WML）和灰质高信号病变（GML）体积，并使用综合神经认知测试评估多个功能领域。线性回归模型用于测试基因型、抑郁与基因型的相互作用以及年龄与基因型的相互作用对两种高信号病变体积测量和神经认知任务表现的影响。
MTHFR C677T 基因型与年龄的相互作用项与 MRI WML 体积显著相关（p=0.0175）；然而，当 WML 体积进行对数转换以产生更正态分布时，这种关系不再具有统计学意义。677T 等位基因在抑郁组中既不更频繁，也与灰质高信号体积或神经认知测试表现无关。
MTHFR 基因型影响年龄与 WML 体积之间的关系，携带 677T 等位基因的个体随年龄增长 WML 体积更大，尽管鉴于使用转换后的 WML 体积未能复制该发现，这一关系需要进一步验证。基因型与 GML 体积、认知功能或抑郁状态无关，尽管人口统计学差异可能导致这一阴性发现。
