Original Article

Citation: Translational Psychiatry (2012) 2, e71; doi:10.1038/tp.2011.68
Published online 24 January 2012

Cardiometabolic risk and the MTHFR C677T variant in children treated with second-generation antipsychotics

A M Devlin1, Y F Ngai1, R Ronsley1 and C Panagiotopoulos1

1Department of Pediatrics, University of British Columbia, Child and Family Research Institute, Vancouver, Canada

Correspondence: Dr AM Devlin, Department of Pediatrics, University of British Columbia, Child and Family Research Institute, 272-950 West 28th Ave, Vancouver V6K 4A9, Canada. E-mail: adevlin@cfri.ubc.ca; Dr C Panagiotopoulos, Department of Pediatrics, University of British Columbia, Endocrinology and Diabetes Unit, British Columbia Children's Hospital, 4480 Oak St, ACB K4-213, Vancouver, V6H 3V4, Canada. E-mail: dpanagiotopoulos@cw.bc.ca

Received 8 November 2011; Revised 9 December 2011; Accepted 11 December 2011



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 greater than or equal to90th percentile for age and sex; plasma triglyceride greater than or equal to1.24mmoll−1; plasma high-density lipoprotein-cholesterol less than or equal to1.03mmoll−1; systolic or diastolic blood pressure greater than or equal to90th percentile for age, sex, and height; and fasting glucose greater than or equal to5.6mmoll−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.


blood pressure; children; impaired fasting glucose; metabolic syndrome; MTHFR; second-generation antipsychotics