Department of Pediatrics, University of British Columbia, Child and Family Research Institute, Vancouver, Canada.
Transl Psychiatry. 2012 Jan 24;2(1):e71. doi: 10.1038/tp.2011.68.
Second-generation antipsychotics (SGAs) are increasingly being used to treat children with a variety of psychiatric illnesses. Metabolic syndrome (MetS), a risk factor for cardiovascular disease, is a side-effect of SGA-treatment. We conducted a cross-sectional study and assessed the association of the methylenetetrahydrofolate reductase (MTHFR) C677T variant with features of MetS in SGA-treated (n=105) and SGA-naïve (n=112) children. We targeted the MTHFR C677T variant, because it is associated with risk for cardiovascular disease, and features of MetS in adults without psychiatric illness. MetS in children is based on the presence of any three of the following: waist circumference ≥ 90th percentile for age and sex; plasma triglyceride ≥ 1.24 mmol l(-1); plasma high-density lipoprotein-cholesterol ≤ 1.03 mmol l(-1); systolic or diastolic blood pressure ≥ 90th percentile for age, sex, and height; and fasting glucose ≥ 5.6 mmol l(-1). We found that 15% of SGA-treated children had MetS compared with 2% of SGA-naïve children (OR 8.113, P<0.05). No effect of the MTHFR C677T variant on psychiatric diagnosis was observed. The MTHFR 677T allele was associated (P<0.05) with MetS (OR 5.75, 95% CI= 1.18-28.12) in SGA-treated children. Models adjusted for duration of SGA treatment, ethnicity, sex, age and use of other medications revealed a positive relationship between the MTHFR 677T allele and diastolic blood pressure Z-scores (P=0.001) and fasting plasma glucose (P<0.05) in SGA-treated children. These findings illustrate the high prevalence of MetS in SGA-treated children and suggest metabolic alterations associated with the MTHFR C677T variant may have a role in the development of MetS features in SGA-treated children.
第二代抗精神病药物（SGAs）越来越多地被用于治疗各种精神疾病的儿童。代谢综合征（MetS）是心血管疾病的一个危险因素，是 SGA 治疗的副作用。我们进行了一项横断面研究，评估了亚甲基四氢叶酸还原酶（MTHFR）C677T 变异与 SGA 治疗（n=105）和 SGA 未治疗（n=112）儿童代谢综合征特征的相关性。我们针对 MTHFR C677T 变异，因为它与心血管疾病风险以及无精神疾病成年人代谢综合征特征相关。儿童代谢综合征基于以下任何三种情况的存在：腰围≥年龄和性别的第 90 百分位；血浆三酰甘油≥1.24mmol·l（-1）；血浆高密度脂蛋白胆固醇≤1.03mmol·l（-1）；收缩压或舒张压≥年龄、性别和身高的第 90 百分位；和空腹血糖≥5.6mmol·l（-1）。我们发现，与 SGA 未治疗的儿童相比，15%的 SGA 治疗的儿童患有代谢综合征（OR 8.113，P<0.05）。MTHFR C677T 变异对精神诊断没有影响。在 SGA 治疗的儿童中，MTHFR 677T 等位基因与代谢综合征（OR 5.75，95%CI=1.18-28.12）相关（P<0.05）。调整 SGA 治疗持续时间、种族、性别、年龄和其他药物使用的模型显示，MTHFR 677T 等位基因与 SGA 治疗儿童的舒张压 Z 评分（P=0.001）和空腹血浆葡萄糖（P<0.05）呈正相关。这些发现说明了 SGA 治疗的儿童中代谢综合征的高患病率，并表明与 MTHFR C677T 变异相关的代谢改变可能在 SGA 治疗的儿童中代谢综合征特征的发展中起作用。
