title: Association of the low-activity COMT 158Met allele with ADHD and OCD in subjects with velocardiofacial syndrome.
abstract: Velocardiofacial syndrome (VCFS) is caused by a microdeletion in chromosome 22 and is a risk factor for the development of schizophrenia and other psychiatric disorders. The catechol-O-methyltransferase (COMT), residing in the 22q11.2 microdeletion region, is a major candidate gene for genetic susceptibility to neuropsychiatric disorders in VCFS. Individuals with VCFS carrying the low-activity allele (COMTL) are expected to have the lowest possible COMT activity since they have only a single copy of the gene. We explored the possibility that COMTL is associated with psychiatric disorders commonly found in VCFS. Fifty-five unrelated individuals with VCFS underwent psychiatric evaluation and were genotyped for the COMT 158Val/Met polymorphism coding for COMT high/low-activity alleles. The COMTL allele was significantly more prevalent in VCFS subjects with attention deficit hyperactivity disorder (ADHD) (73.9% vs. 33.3%, OR 5.67, chi2=7.76, p=0.005) and obsessive-compulsive disorder (OCD) (78.6% vs. 33.3%, OR 7.33, chi2=7.24, p=0.007) than in the control group (VCFS subjects without OCD, ADHD and schizophrenia/schizoaffective (SZ/SZaff) disorder). The results of this study suggest that greatly reduced COMT activity, as expected in VCFS COMTL individuals may be a risk factor for psychiatric sequelae in this population. Future longitudinal studies focusing on additional COMT polymorphic sites and other candidate genes from the deleted region will elucidate the molecular pathways leading to schizophrenia and other psychiatric disorders in VCFS.
authors.affiliation: The Behavioral Neurogenetics Center, Feinberg Child Study Center, Schneider Children's Medical Center of Israel, Petah Tiqwa 49202, Israel. gothelf@post.tan.ac.il
authors.forename: Doron
authors.initials: D
authors.lastname: Gothelf
authors.forename: Elena
authors.initials: E
authors.lastname: Michaelovsky
authors.forename: Amos
authors.initials: A
authors.lastname: Frisch
authors.forename: Ada H
authors.initials: AH
authors.lastname: Zohar
authors.forename: Gadi
authors.initials: G
authors.lastname: Presburger
authors.forename: Merav
authors.initials: M
authors.lastname: Burg
authors.forename: Ayala
authors.initials: A
authors.lastname: Aviram-Goldring
authors.forename: Moshe
authors.initials: M
authors.lastname: Frydman
authors.forename: Josepha
authors.initials: J
authors.lastname: Yeshaya
authors.forename: Mordechai
authors.initials: M
authors.lastname: Shohat
authors.forename: Michael
authors.initials: M
authors.lastname: Korostishevsky
authors.forename: Alan
authors.initials: A
authors.lastname: Apter
authors.forename: Abraham
authors.initials: A
authors.lastname: Weizman
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000523:psychology; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003071:Cognition / Q000502:physiology; D003627:Data Interpretation, Statistical; D004062:DiGeorge Syndrome / Q000235:genetics* / Q000523:psychology; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics; D009483:Neuropsychological Tests; D009771:Obsessive-Compulsive Disorder / Q000235:genetics* / Q000523:psychology; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics
chemical_list: D008715:Methionine; D002394:Catechol O-Methyltransferase