Glutamatergic Copy Number Variants and Their Role in Attention-Deficit/Hyperactivity Disorder

被引：26

作者：

Akutagava-Martins, Glaucia Chiyoko ^{[1
]}

Salatino-Oliveira, Angelica ^{[1
]}

Genro, Julia P. ^{[1
]}

Contini, Veronica ^{[1
]}

Polanczyk, Guilherme ^{[2
]}

Zeni, Cristian ^{[3
]}

Chazan, Rodrigo ^{[3
]}

Kieling, Christian ^{[3
]}

Anselmi, Luciana ^{[4
]}

Menezes, Ana M. B. ^{[4
]}

Grevet, Eugenio H. ^{[5
]}

Bau, Claiton H. D. ^{[1
,5
]}

Rohde, Luis A. ^{[3
]}

Hutz, Mara H. ^{[1
]}

机构：

[1] Univ Fed Rio Grande do Sul, Dept Genet, BR-91501970 Porto Alegre, RS, Brazil

[2] Univ Sao Paulo, Dept Psychiat, BR-05508 Sao Paulo, Brazil

[3] Hosp Clin Porto Alegre, Div Child & Adolescent Psychiat, Porto Alegre, RS, Brazil

[4] Univ Fed Pelotas, Postgrad Program Epidemiol, Capao Do Leao, RS, Brazil

[5] Hosp Clin Porto Alegre, Adult ADHD Outpatient Program, Porto Alegre, RS, Brazil

来源：

AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS | 2014年 / 165卷 / 06期

关键词：

GRM1; GRM5; GRM8; IQ; anxiety; DEFICIT HYPERACTIVITY DISORDER; GENOME-WIDE ASSOCIATION; FEAR EXTINCTION; ADHD; PREVALENCE; PLASTICITY; RECEPTOR; METAANALYSIS; CHILDREN; CONTEXT;

D O I：

10.1002/ajmg.b.32253

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Attention-Deficit/Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder with a strong genetic component. The glutamate metabotropic receptor genes (GRMs) have been considered potential candidates for ADHD susceptibility. The aim of the present study was to investigate if copy number variants (CNVs) in GRM1, GRM5, and GRM8 genes are over-represented in ADHD subjects. A total of 1038 individuals with ADHD and 1057 subjects without this disorder were investigated. No significant difference in the total number of CNVs was found comparing the entire ADHD sample and the population sample without ADHD (P = 0.326, OR = 1.112, 95% CI = 0.762-1.624). The presence of CNVs was associated with lower intelligence quotient (IQ) scores in ADHD samples (P = 0.026, OR = 1.824,95% CI = 1.066-3.121) but not in the sample of individuals without ADHD. CNVs in GRM5 were associated with presence of anxiety disorders in ADHD cases (P = 0.002, OR = 3.915, 95% CI = 1.631-9.402), but not in individuals without ADHD. Taken together, our results suggest a role for glutamate in ADHD as CNVs in the glutamatergic genes investigated herein were associated with cognitive and clinical characteristics of ADHD individuals. (C) 2014 Wiley Periodicals, Inc.

引用

页码：502 / 509

页数：8

共 48 条

[11] Accurate and objective copy number profiling using real-time quantitative PCR [J].

D'haene, Barbara ;

Vandesompele, Jo ;

Hellemans, Jan .

METHODS, 2010, 50 (04) :262-270

[12] Validity and applicability of the Mini International Neuropsychiatric Interview administered by family medicine residents in primary health care in Brazil [J].

de Azevedo Marques, Joao Mazzoncini ;

Zuardi, Antonio W. .

GENERAL HOSPITAL PSYCHIATRY, 2008, 30 (04) :303-310

[13] Rare structural variants found in attention-deficit hyperactivity disorder are preferentially associated with neurodevelopmental genes [J].

Elia, J. ;

Gai, X. ;

Xie, H. M. ;

Perin, J. C. ;

Geiger, E. ;

Glessner, J. T. ;

D'arcy, M. ;

deBerardinis, R. ;

Frackelton, E. ;

Kim, C. ;

Lantieri, F. ;

Muganga, B. M. ;

Wang, L. ;

Takeda, T. ;

Rappaport, E. F. ;

Grant, S. F. A. ;

Berrettini, W. ;

Devoto, M. ;

Shaikh, T. H. ;

Hakonarson, H. ;

White, P. S. .

MOLECULAR PSYCHIATRY, 2010, 15 (06) :637-646

[14] Genome-wide copy number variation study associates metabotropic glutamate receptor gene networks with attention deficit hyperactivity disorder [J].

Elia, Josephine ;

Glessner, Joseph T. ;

Wang, Kai ;

Takahashi, Nagahide ;

Shtir, Corina J. ;

Hadley, Dexter ;

Sleiman, Patrick M. A. ;

Zhang, Haitao ;

Kim, Cecilia E. ;

Robison, Reid ;

Lyon, Gholson J. ;

Flory, James H. ;

Bradfield, Jonathan P. ;

Imielinski, Marcin ;

Hou, Cuiping ;

Frackelton, Edward C. ;

Chiavacci, Rosetta M. ;

Sakurai, Takeshi ;

Rabin, Cara ;

Middleton, Frank A. ;

Thomas, Kelly A. ;

Garris, Maria ;

Mentch, Frank ;

Freitag, Christine M. ;

Steinhausen, Hans-Christoph ;

Todorov, Alexandre A. ;

Reif, Andreas ;

Rothenberger, Aribert ;

Franke, Barbara ;

Mick, Eric O. ;

Roeyers, Herbert ;

Buitelaar, Jan ;

Lesch, Klaus-Peter ;

Banaschewski, Tobias ;

Ebstein, Richard P. ;

Mulas, Fernando ;

Oades, Robert D. ;

Sergeant, Joseph ;

Sonuga-Barke, Edmund J. S. ;

Renner, Tobias J. ;

Romanos, Marcel ;

Romanos, Jasmin ;

Warnke, Andreas ;

Walitza, Susanne ;

Meyer, Jobst ;

Palmason, Haukur ;

Seitz, Christiane ;

Loo, Sandra K. ;

Smalley, Susan L. ;

Biederman, Joseph .

NATURE GENETICS, 2012, 44 (01) :78-U113

[15]

Elia J, 2011, LANCET, V377, P377, DOI 10.1016/S0140-6736(11)60120-7

[16] The age-dependent decline of attention deficit hyperactivity disorder: a meta-analysis of follow-up studies [J].

Faraone, SV ;

Biederman, J ;

Mick, E .

PSYCHOLOGICAL MEDICINE, 2006, 36 (02) :159-165

[17] G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences [J].

Faul, Franz ;

Erdfelder, Edgar ;

Lang, Albert-Georg ;

Buchner, Axel .

BEHAVIOR RESEARCH METHODS, 2007, 39 (02) :175-191

[18] The effect of mGlu8 deficiency in animal models of psychiatric diseases [J].

Fendt, M. ;

Buerki, H. ;

Imobersteg, S. ;

van der Putten, H. ;

McAllister, K. ;

Leslie, J. C. ;

Shaw, D. ;

Hoelscher, C. .

GENES BRAIN AND BEHAVIOR, 2010, 9 (01) :33-44

[19] COMORBIDITY AND DISEASE BURDEN IN THE NATIONAL COMORBIDITY SURVEY REPLICATION (NCS-R) [J].

Gadermann, Anne M. ;

Alonso, Jordi ;

Vilagut, Gemma ;

Zaslavsky, Alan M. ;

Kessler, Ronald C. .

DEPRESSION AND ANXIETY, 2012, 29 (09) :797-806

[20] Attention-deficit/hyperactivity disorder and the dopaminergic hypotheses [J].

Genro, Julia P. ;

Kieling, Christian ;

Rohde, Luis A. ;

Hutz, Mara H. .

EXPERT REVIEW OF NEUROTHERAPEUTICS, 2010, 10 (04) :587-601

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