Description:
<jats:p>Second‐generation antipsychotics (SGA) are used to treat children for a wide‐range of mental health conditions but are associated with side effects such as rapid weight gain; increased waist circumference; and elevated fasting plasma glucose, blood pressure, and metabolic syndrome (MetS). The aim of this study is to investigate the interaction of the rs4680 variant in the catechol‐ O‐methyltransferase gene (<jats:italic>COMT</jats:italic>) and SGA treatment on cardiometabolic side‐effects in a cross‐sectional population of SGA‐treated (n=99) and SGA–naïve (n=114) children. SGA‐treated children had higher (<jats:italic>P</jats:italic><0.05) BMI z‐scores, systolic blood pressure (SBP) z‐scores, and fasting plasma glucose and total and LDL‐cholesterol concentrations than SGA‐naïve children. Fifteen percent of SGA‐treated children had MetS compared to 2% of SGA‐naïve children (<jats:italic>P</jats:italic>=0.001). The <jats:italic>COMT</jats:italic> rs4680 variant genotype frequencies were not different between SGA‐treated (AA 24.2%, AG 50.5%, GG 25.3%) and SGA‐naïve (AA 24.6%, GA 45.6%, GG 29.8%) children. An interaction between SGA‐treatment and <jats:italic>COMT</jats:italic> rs4680 genotype was observed such that SGA‐treated children with the AA genotype had higher SBP, fasting plasma insulin, and HOMA‐IR than those with the GG genotype. The opposite effect was observed in SGA‐naïve children. These findings suggest that the <jats:italic>COMT</jats:italic> rs4680 variant may interact with SGAs and contribute to cardiometabolic side‐effects in children.</jats:p>