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

被引:57
作者
Gothelf, Doron
Michaelovsky, Elena
Frisch, Amos
Zohar, Ada H.
Presburger, Gadi
Burg, Merav
Aviram-Goldring, Ayala
Frydman, Moshe
Yeshaya, Josepha
Shohat, Mordechai
Korostishevsky, Michael
Apter, Alan
Weizman, Abraham
机构
[1] Schneider Childrens Med Ctr Israel, Dept Child Psychiat, Feinberg Child Study Ctr, Behav Neurogenet Ctr, IL-49202 Petah Tiqwa, Israel
[2] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel
[3] Tel Aviv Univ, Felsenstein Med Res Ctr, IL-49100 Petah Tiqwa, Israel
[4] Ruppin Acad Ctr, Dept Behav Sci, Emek Hefer, Israel
[5] Chaim Sheba Med Ctr, Danek Gertner Inst Human Genet, IL-52621 Tel Hashomer, Israel
[6] Rabin Med Ctr, Dept Med Genet, Petah Tiqwa, Israel
[7] Geha Mental Hlth Ctr, Res Unit, Petah Tiqwa, Israel
关键词
attention deficit hyperactivity disorder; obsessive-compulsive disorder; polymorphism; schizophrenia; 22q11.2; deletion;
D O I
10.1017/S1461145706006699
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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 (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 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.
引用
收藏
页码:301 / 308
页数:8
相关论文
共 57 条
  • [1] Association between the COMT locus and obsessive-compulsive disorder in females but not males
    Alsobrook, JP
    Zohar, AH
    Leboyer, M
    Chabane, N
    Ebstein, RP
    Pauls, DL
    [J]. AMERICAN JOURNAL OF MEDICAL GENETICS, 2002, 114 (01): : 116 - 120
  • [2] Velo-cardio-facial syndrome: Implications of microdeletion 22q11 for schizophrenia and mood disorders
    Arnold, PD
    Siegel-Bartelt, J
    Cytrynbaum, C
    Teshima, I
    Schachar, R
    [J]. AMERICAN JOURNAL OF MEDICAL GENETICS, 2001, 105 (04): : 354 - 362
  • [3] Meta-analysis of the association between the catecholamine-O-methyl-transferase gene and obsessive-compulsive disorder
    Azzam, A
    Mathews, CA
    [J]. AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS, 2003, 123B (01) : 64 - 69
  • [4] COMT Val108/158Met modifies mismatch negativity and cognitive function in 22q11 deletion syndrome
    Baker, K
    Baldeweg, T
    Sivagnanasundaram, S
    Scambler, P
    Skuse, D
    [J]. BIOLOGICAL PSYCHIATRY, 2005, 58 (01) : 23 - 31
  • [5] 22q11 deletion syndrome: A genetic subtype of schizophrenia
    Bassett, AS
    Chow, EWC
    [J]. BIOLOGICAL PSYCHIATRY, 1999, 46 (07) : 882 - 891
  • [6] Bassett AS, 1998, AM J MED GENET, V81, P328, DOI 10.1002/(SICI)1096-8628(19980710)81:4<328::AID-AJMG10>3.3.CO
  • [7] 2-8
  • [8] The schizophrenia phenotype in 22q11 deletion syndrome
    Bassett, AS
    Chow, EWC
    AbdelMalik, P
    Gheorghiu, M
    Husted, J
    Weksberg, R
    [J]. AMERICAN JOURNAL OF PSYCHIATRY, 2003, 160 (09) : 1580 - 1586
  • [9] Effects of COMT genotype on behavioral symptomatology in the 22q11.2 Deletion Syndrome
    Bearden, CE
    Jawad, AF
    Lynch, DR
    Monterossso, JR
    Sokol, S
    McDonald-McGinn, DM
    Saitta, SC
    Harris, SE
    Moss, E
    Wang, PP
    Zackai, E
    Emanuel, BS
    Simon, TJ
    [J]. CHILD NEUROPSYCHOLOGY, 2005, 11 (01) : 109 - 117
  • [10] Effects of a functional COMT polymorphism on prefrontal cognitive function in patients with 22q11.2 deletion syndrome
    Bearden, CE
    Jawad, AF
    Lynch, DR
    Sokol, S
    Kanes, SJ
    McDonald-McGinn, DM
    Saitta, SC
    Harris, SE
    Moss, E
    Wang, PP
    Zackai, E
    Emanuel, BS
    Simon, TJ
    [J]. AMERICAN JOURNAL OF PSYCHIATRY, 2004, 161 (09) : 1700 - 1702