COMT genotype predicts longitudinal cognitive decline and psychosis in 22q11.2 deletion syndrome

Nat Neurosci. 2005 Nov;8(11):1500-2. doi: 10.1038/nn1572. Epub 2005 Oct 23.


Although schizophrenia is strongly hereditary, there are limited data regarding biological risk factors and pathophysiological processes. In this longitudinal study of adolescents with 22q11.2 deletion syndrome, we identified the catechol-O-methyltransferase low-activity allele (COMT(L)) as a risk factor for decline in prefrontal cortical volume and cognition, as well as for the consequent development of psychotic symptoms during adolescence. The 22q11.2 deletion syndrome is a promising model for identifying biomarkers related to the development of schizophrenia.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Analysis of Variance
  • Catechol O-Methyltransferase / genetics*
  • Chromosomes, Human, Pair 22*
  • Cognition Disorders / etiology
  • Cognition Disorders / genetics*
  • DiGeorge Syndrome / complications
  • DiGeorge Syndrome / enzymology*
  • DiGeorge Syndrome / genetics*
  • Female
  • Gene Deletion*
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging / methods
  • Male
  • Neuropsychological Tests
  • Polymorphism, Genetic
  • Predictive Value of Tests
  • Psychiatric Status Rating Scales
  • Risk Factors


  • Catechol O-Methyltransferase