title: 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.affiliation: Department of Psychiatry, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands. m.b.dekoning@amc.uva.nl
authors.forename: Mariken B
authors.initials: MB
authors.lastname: de Koning
authors.forename: Erik
authors.initials: E
authors.lastname: Boot
authors.forename: Oswald J N
authors.initials: OJ
authors.lastname: Bloemen
authors.forename: Esther D A
authors.initials: ED
authors.lastname: van Duin
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Abel
authors.forename: Lieuwe
authors.initials: L
authors.lastname: de Haan
authors.forename: Don H
authors.initials: DH
authors.lastname: Linszen
authors.forename: Thérèse A M J
authors.initials: TA
authors.lastname: van Amelsvoort
mesh_terms: D058165:22q11 Deletion Syndrome / Q000235:genetics*; D000161:Acoustic Stimulation; D000328:Adult; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D005838:Genotype; D057898:Hemizygote; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D017397:Prefrontal Cortex / Q000473:pathology; D013216:Reflex, Startle / Q000235:genetics*; D055815:Young Adult
chemical_list: D002394:Catechol O-Methyltransferase; D004298:Dopamine