Startle reactivity and prepulse inhibition of the acoustic startle response are modulated by catechol-O-methyl-transferase Val(158) Met polymorphism in adults with 22q11 deletion syndrome

Mariken B. de Koning*, Erik Boot, Oswald J. N. Bloemen, Esther D. A. van Duin, Kathryn M. Abel, Lieuwe de Haan, Don H. Linszen, Therese A. M. J. van Amelsvoort

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


22q11 deletion syndrome (22q11DS) is a genetic disorder caused by a microdeletion on chromosome 22, which includes the gene coding for catechol-O-methyl-transferase (COMT). High dopamine (DA) levels due to COMT haplo-insufficiency may be associated with the increased risk of developing schizophrenia in adults with 22q11DS. Reduced prepulse inhibition (PPI) of the acoustic startle response has been associated with schizophrenia and with disrupted DAergic transmission in the prefrontal cortex (PFC). COMT Val158Met polymorphism has been shown to influence PPI. We report the first study in adults with 22q11DS to examine PPI of the acoustic startle response and its modulation by COMT Val158Met polymorphism. Startle reactivity (SR) and PPI of the acoustic startle response were measured in 23 adults with 22q11DS and 21 healthy controls. 22q11DS subjects were genotyped for the functional COMT Val158Met polymorphism. 22q11DS Met hemizygotes showed reduced SR and PPI compared with 22q11DS Val hemizygotes. The effect of COMT Val158Met polymorphism on PPI was no longer significant when controlling for baseline SR. Met hemizygosity in 22q11DS is associated with reduced SR and influences PPI indirectly. Decreased PFC functioning following excessive PFC DA levels may be one of the mechanisms by which the Met genotype in 22q11DS disrupts SR.
Original languageEnglish
Pages (from-to)1548-1560
JournalJournal of Psychopharmacology
Issue number12
Publication statusPublished - Dec 2012


  • Dopamine
  • COMT
  • 22q11 deletion syndrome
  • velo-cardio-facial syndrome
  • prepulse inhibition
  • startle reactivity

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