Association of the low-activity COMT (158)Met allele with ADHD and OCD in subjects with velocardiofacial syndrome

作者：Gothelf Doron^*; Michaelovsky Elena; Frisch Amos; Zohar Ada H; Pre**urger Gadi; Burg Merav; Aviram Goldring Ayala; Frydman Moshe; Yeshaya Josepha; Shohat Mordechai; Korostishevsky Michael; Apter Alan; Weizman Abraham

来源：International Journal of Neuropsychopharmacology, 2007, 10(3): 301-308.

DOI：10.1017/S1461145706006699

• attention deficit hyperactivity disorder
• obsessive-compulsive disorder
• polymorphism
• schizophrenia
• 22q11.2 deletion

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 (COMT(L)) 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 (158)Val/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, chi(2)=7.76, p=0.005) and obsessive-compulsive disorder (OCD) (78.6% vs. 33.3 %, OR 7.33, chi(2) = 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 COMT(L) 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.

• 出版日期2007-6
• 单位上海市精神卫生中心