Research Centre for Prevention and Health, The Capital Region of Denmark, Copenhagen, Denmark.
Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Eur J Clin Nutr. 2017 Sep;71(9):1054-1060. doi: 10.1038/ejcn.2017.97. Epub 2017 Jun 28.
BACKGROUND/OBJECTIVES: Observational studies have suggested low serum levels of vitamin B12 or folate to be risk factors of depression and anxiety. However, these results may be biased by confounding and reverse causation. Mendelian randomization studies are not subject to these limitations. The aim was to examine the association of genetic scores of vitamin B12 and folate-associated alleles with depression and anxiety.
SUBJECTS/METHODS: The study included 4126 participants from two Danish population-based studies. Serum vitamin B12 and folate were measured. Weighed allele scores were calculated as the sum of weights (genetic effect sizes) for 12 and two variants increasing circulating levels of vitamin B12 and folate, respectively. Symptoms of depression and anxiety were assessed by the Symptom Check List (SCL)-90-R, and self-reported doctor-diagnosed depression and anxiety.
An increased weighed allele score for serum vitamin B12 was associated with decreased odds of a SCL-90-R score above the 90th percentile (OR 0.540 (95%CI 0.302-0.967)) in Health2006 but not in Inter99, in the pooled analysis (OR 0.817 (95%CI 0.331-2.018)) or with other outcomes. The weighed allele score for serum folate was not associated with any of the measured outcome variables: SCL-90-R scores of depression (pooled OR 0.603 (95%CI 0.101-3.602)), anxiety (pooled OR 0.619 (95%CI 0.110-3.495)), combined score or history of doctor-diagnosed depression or anxiety.
Our results do not provide evidence for a causal effect of circulating folate or vitamin B12 on the risk of depression or anxiety. However, we cannot rule out small to moderate effects, and thus large scale studies are needed.
背景/目的：观察性研究表明，血清维生素 B12 或叶酸水平低可能是抑郁和焦虑的危险因素。然而，这些结果可能受到混杂因素和反向因果关系的影响。孟德尔随机化研究不受这些限制。本研究旨在探讨血清维生素 B12 和叶酸相关等位基因的遗传评分与抑郁和焦虑的相关性。
受试者/方法：本研究纳入了来自丹麦两项基于人群的研究的 4126 名参与者。测量了血清维生素 B12 和叶酸。加权等位基因评分计算为分别增加循环维生素 B12 和叶酸水平的 12 个和 2 个变异体的加权（遗传效应大小）总和。使用症状检查表（SCL-90-R）评估抑郁和焦虑症状，以及自我报告的医生诊断的抑郁和焦虑。
血清维生素 B12 的加权等位基因评分升高与 Health2006 中 SCL-90-R 评分高于第 90 百分位数的几率降低相关（OR 0.540（95%CI 0.302-0.967）），但在 Inter99 中不相关（OR 0.817（95%CI 0.331-2.018））或与其他结局相关。血清叶酸的加权等位基因评分与任何测量的结局变量均无关联：SCL-90-R 抑郁评分（汇总 OR 0.603（95%CI 0.101-3.602））、焦虑评分（汇总 OR 0.619（95%CI 0.110-3.495））、综合评分或医生诊断的抑郁或焦虑病史。
我们的结果没有提供循环叶酸或维生素 B12 对抑郁或焦虑风险的因果效应的证据。然而，我们不能排除小到中度的影响，因此需要进行大规模的研究。
