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.

Abstract	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 Val(158)Met 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 Val(158)Met 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 Val(158)Met polymorphism. 22q11DS Met hemizygotes showed reduced SR and PPI compared with 22q11DS Val hemizygotes. The effect of COMT Val(158)Met 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.
Authors	Mariken B de Koning, Erik Boot, Oswald J N Bloemen, Esther D A van Duin, Kathryn M Abel, Lieuwe de Haan, Don H Linszen, Thérèse A M J van Amelsvoort
Journal	Journal of psychopharmacology (Oxford, England) (J Psychopharmacol) Vol. 26 Issue 12 Pg. 1548-60 (Dec 2012) ISSN: 1461-7285 [Electronic] United States
PMID	22952320 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Catechol O-Methyltransferase Dopamine
Topics	22q11 Deletion Syndrome (genetics) Acoustic Stimulation Adult Case-Control Studies Catechol O-Methyltransferase (genetics) Dopamine (metabolism) Female Genotype Hemizygote Humans Male Polymorphism, Genetic Prefrontal Cortex (pathology) Reflex, Startle (genetics) Young Adult

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