Effects of Comt Genotype on Behavioral Symptomatology in the 22q11.2 Deletion Syndrome

Abstract

The 22q11.2 Deletion Syndrome (DiGeorge/velocardiofacial syndrome) is associated with elevated rates of psychosis, and is also characterized by severe attentional difficulties and executive dysfunction. Behavioral manifestations of this syndrome could result from haploinsufficiency of the catechol-O-methyltransferase (COMT) gene, located within the 22q11 region. The goal of the present study was to examine COMT genotype in relation to behavioral symptomatology in this syndrome. Val^158/108Met was genotyped in 38 patients (16 Met/-, 22 Val/-) with confirmed 22q11.2 deletions who had received the Child Behavior Checklist (CBCL) as part of a comprehensive evaluation. Results indicated that the Val genotype was associated with significantly greater internalizing and externalizing behavioral symptomatology in children with 22q11.2 deletions. Val allele status was associated with a greater-than-four-fold increase in risk for clinically significant behavior problems in children with this syndrome. These data are consistent with previous findings of increased psychopathology associated with the Val genotype in normal individuals and suggest that a functional genetic polymorphism in the 22q11 region may influence behavior in individuals with COMT haploinsufficiency.

Keywords:

• 22q11.2 deletion
• velocardiofacial syndrome
• COMT polymorphism
• genotype
• Child Behavior Checklist
• psychopathology

Acknowledgments

This work was partially supported by NIH grant PO1-DC02027 (B.S.E.) and a Beeson Award from the American Federation for Aging Research. (D.R.L.)

The authors thank M. F. Woodin for assistance with data collection, and the patients and their families for participation in the study.