Randomized multicenter investigation of folate plus vitamin B12 supplementation in schizophrenia.
Randomized multicenter investigation of folate plus vitamin B12 supplementation in schizophrenia.
复制标题
精神分裂症中补充叶酸加维生素B12的随机多中心研究。
DOI：
10.1001/jamapsychiatry.2013.900
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发表时间：
2013-05
期刊：
影响因子：
25.8
通讯作者：
Goff, Donald C.
中科院分区：
文献类型：
--
作者：
Roffman, Joshua L.;Lamberti, J. Steven;Achtyes, Eric;Macklin, Eric A.;Galendez, Gail C.;Raeke, Lisa H.;Silverstein, Noah J.;Smoller, Jordan W.;Hill, Michele;Goff, Donald C.
精神分裂症的阴性症状对抗精神病药物的反应最小，以前与血液叶酸水平降低有关，特别是在调节叶酸代谢的基因中具有低功能变体的患者中。确定叶酸加B12补充剂是否减少精神分裂症的阴性症状，以及叶酸相关基因的功能变异是否影响治疗反应。2 mg叶酸和400 mcg B12治疗16周的随机、双盲、安慰剂对照临床试验。三个社区精神健康中心附属于美国的学术医疗中心。服用稳定剂量抗精神病药物的慢性精神分裂症门诊患者。140名受试者随机接受每日口服叶酸加B12或安慰剂。阴性症状（阴性症状评估量表，SANS）以及阳性和总症状（阳性和阴性症状量表）的变化。当考虑基因型时，与安慰剂相比，叶酸加B12显著改善阴性症状（组间差异：每周SANS变化-0.33; 95% CI，-0.62至-0.05），但当排除基因型时则无此差异。观察到FOLH 1的484 C>T变体（rs 202676）与治疗的相互作用（p= 0.02），其中仅484 T等位基因纯合的患者显示出活性治疗的显著更大益处（SANS每周变化-0.59，95%CI，-0.99至-0.18）。同时，我们观察到基线时红细胞叶酸浓度与484 C等位基因负荷之间的负相关关系（p= 0.03），这种关系一直持续到治疗8周。治疗组之间阳性症状和总症状的变化无差异。叶酸加B12补充剂可以改善精神分裂症的阴性症状，但治疗反应受到叶酸吸收遗传变异的影响。这些发现支持了治疗阴性症状的个性化医学方法。ClinicalTrials.gov www.example.com
Negative symptoms of schizophrenia, which respond minimally to antipsychotic medications, have previously been associated with reduced blood folate levels, especially among patients with low-functioning variants in genes that regulate folate metabolism. To determine whether folic acid plus B12 supplementation reduces negative symptoms of schizophrenia, and whether functional variants in folate-related genes influence treatment response. Parallel-group, randomized, double-blind, placebo-controlled clinical trial of 16 weeks of treatment with 2 mg folic acid and 400 mcg B12. Three community mental health centers affiliated with academic medical centers in the United States. Outpatients with chronic schizophrenia taking stable doses of antipsychotic medications. 140 subjects were randomized to receive daily oral folic acid plus B12 or placebo. Change in negative symptoms (Scale for Assessment of Negative Symptoms, SANS), as well as positive and total symptoms (Positive and Negative Syndrome Scale). Folate plus B12 improved negative symptoms significantly compared to placebo (group difference: -0.33 change in SANS per week; 95% CI, -0.62 to -0.05) when genotype was taken into account, but not when genotype was excluded. An interaction of the 484C>T variant of FOLH1 (rs202676) with treatment was observed (p=.02), where only patients homozygous for the 484T allele demonstrated significantly greater benefit with active treatment (-0.59 change in SANS per week, 95% CI, -0.99 to -0.18). In parallel we observed an inverse relationship between red blood cell folate concentration at baseline and 484C allele load (p=.03), which persisted until 8 weeks of treatment. Change in positive and total symptoms did not differ between treatment groups. Folate plus B12 supplementation can improve negative symptoms of schizophrenia, but treatment response is influenced by genetic variation in folate absorption. These findings support a personalized medicine approach for the treatment of negative symptoms. ClinicalTrials.gov NCT00611806
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DOI：
10.1073/pnas.062066299
发表时间：
2002-04-16
影响因子：
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作者：
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