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
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
收藏
页码:502 / 509
页数:8
相关论文
共 48 条
[1]   REDUCED HIPPOCAMPAL LONG-TERM POTENTIATION AND CONTEXT-SPECIFIC DEFICIT IN ASSOCIATIVE LEARNING IN MGLUR1 MUTANT MICE [J].
AIBA, A ;
CHEN, C ;
HERRUP, K ;
ROSENMUND, C ;
STEVENS, CF ;
TONEGAWA, S .
CELL, 1994, 79 (02) :365-375
[2]   REDUCED HIPPOCAMPAL LONG-TERM POTENTIATION AND CONTEXT-SPECIFIC DEFICIT IN ASSOCIATIVE LEARNING IN MGLUR1 MUTANT MICE [J].
AIBA, A ;
CHEN, C ;
HERRUP, K ;
ROSENMUND, C ;
STEVENS, CF ;
TONEGAWA, S .
CELL, 1994, 79 (02) :365-375
[3]  
Akutagava-Martins GC, 2013, EXPERT REV NEUROTHER, V13, P435, DOI [10.1586/ERN.13.30, 10.1586/ern.13.30]
[4]  
American Psychiatric Association, 2013, Diagnostic and statistical manual of mental disorders, DOI 10.1176/appi.books.9780890425596
[5]  
[Anonymous], REV BRAS PSIQUIATR
[6]  
[Anonymous], 1996, STRUCTURED CLIN INTE
[7]   Fear extinction in rodents: basic insight to clinical promise [J].
Barad, M .
CURRENT OPINION IN NEUROBIOLOGY, 2005, 15 (06) :710-715
[8]   CONTEXT, TIME, AND MEMORY RETRIEVAL IN THE INTERFERENCE PARADIGMS OF PAVLOVIAN LEARNING [J].
BOUTON, ME .
PSYCHOLOGICAL BULLETIN, 1993, 114 (01) :80-99
[9]  
Carter MJ, 2014, THER RECREAT J, V48, P275
[10]   Children with ADHD Symptoms Have a Higher Risk for Reading, Spelling and Math Difficulties in the GINIplus and LISAplus Cohort Studies [J].
Czamara, Darina ;
Tiesler, Carla M. T. ;
Kohlboeck, Gabriele ;
Berdel, Dietrich ;
Hoffmann, Barbara ;
Bauer, Carl-Peter ;
Koletzko, Sibylle ;
Schaaf, Beate ;
Lehmann, Irina ;
Herbarth, Olf ;
von Berg, Andrea ;
Mueller-Myhsok, Bertram ;
Schulte-Koerne, Gerd ;
Heinrich, Joachim .
PLOS ONE, 2013, 8 (05)