title: Cardiometabolic risk and the MTHFR C677T variant in children treated with second-generation antipsychotics.
abstract: 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.
authors: Department of Pediatrics, University of British Columbia, Child and Family Research Institute, Vancouver, Canada.
authors: A M
authors: AM
authors: Devlin
authors: Y F
authors: YF
authors: Ngai
authors: R
authors: R
authors: Ronsley
authors: C
authors: C
authors: Panagiotopoulos
mesh_terms: D000293:Adolescent; D000483:Alleles; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000235:genetics; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000235:genetics*; D002648:Child; D008076:Cholesterol, HDL / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy* / Q000235:genetics*; D024821:Metabolic Syndrome / Q000139:chemically induced* / Q000235:genetics*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D012016:Reference Values; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D014150:Antipsychotic Agents; D001786:Blood Glucose; D008076:Cholesterol, HDL; D014280:Triglycerides; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)