Pilot Study Revealed Association of DRD4 Promoter Variants with ADHD Associated Functional Deficit in Indian Probands
Keywords:
ADHD; molecular genetics; cognitive impairment; learning difficulties
Abstract
Background: Attention Deficit Hyperactivity Disorder (ADHD) is often associated with cognitive deficit. Since brain regions regulating cognition has higher expression of Dopamine receptor 4 (DRD4), we explored association between functional DRD4 promoter variants and cognition of ADHD probands. Methods: Subjects recruited following DSM-IV-TR were assessed for Short Attention Span (SAS) and Erratic Organization Capability (EOC), based on scores obtained through Conner's Parent Rating Scale and DSM-IV-TR as well as computerized games. Functional variants were analyzed in ADHD probands, their parents and age-matched controls. Results: Probands exhibited significant impairment in SAS and EOC. rs10902180, rs747303, rs936462, showed association with cognitive deficit. Probands with co-morbid learning disability showed higher cognitive impairment. Significant interactive effects were evident between the markers. Conclusion: Impaired in information processing and scholastic performance, strong genotype-phenotype correlations more robust in ADHD cases with learning difficulty, suggest significant contribution of DRD4 in ADHD etiology, possibly due to attenuated receptor functioning.
Downloads
- Article PDF
- TEI XML Kaleidoscope (download in zip)* (Beta by AI)
- Lens* NISO JATS XML (Beta by AI)
- HTML Kaleidoscope* (Beta by AI)
- DBK XML Kaleidoscope (download in zip)* (Beta by AI)
- LaTeX pdf Kaleidoscope* (Beta by AI)
- EPUB Kaleidoscope* (Beta by AI)
- MD Kaleidoscope* (Beta by AI)
- FO Kaleidoscope* (Beta by AI)
- BIB Kaleidoscope* (Beta by AI)
- LaTeX Kaleidoscope* (Beta by AI)
How to Cite
References
Nakao T, Radua J, Rubia K (2011) Gray Matter Volume Abnormalities in ADHD: Voxel-Based Meta-Analysis Exploring the Effects of Age and Stimulant Medication. 168(11), 1154-1163. https://doi.org/10.1176/appi.ajp.2011.11020281
Erika Proal, P. Reiss, R. Klein (2011) Brain Gray Matter Deficits at 33-Year Follow-up in Adults With Attention-Deficit/Hyperactivity Disorder Established in Childhood. 68(11), 1122. https://doi.org/10.1001/archgenpsychiatry.2011.117
(2000) Diagnostic and Statistical Manual for Mental Disorders.
Pliszka SR, Glahn DC, Semrud-Clikeman M (2006) Neuroimaging of Inhibitory Control Areas in Children With Attention Deficit Hyperactivity Disorder Who Were Treatment Naive or in Long-Term Treatment. 163(6), 1052-1060. https://doi.org/10.1176/ajp.2006.163.6.1052
Sergeant Salum GA, et. Sonuga-Barke E (2014) Specificity of basic information processing and inhibitory control in attention deficit hyperactivity disorder. 44(3), 617-631. https://doi.org/10.1017/s0033291713000639
Young De, C. Hirsh, J. Shane, M. (2010) Testing predictions from personality neuroscience. 21(6), 820-828.
Jai Yu, Loren Frank (2015) Hippocampal-cortical interaction in decision making. 117, 34-41. https://doi.org/10.1016/j.nlm.2014.02.002
Joseph Price (1999) Prefrontal Cortical Networks Related to Visceral Function and Mood. 877(1), 383-396. https://doi.org/10.1111/j.1749-6632.1999.tb09278.x
Watanabe J, Sugiura M, Sato K (2002) The Human Prefrontal and Parietal Association Cortices Are Involved in NO-GO Performances: An Event-Related fMRI Study. 17(3), 1207-1216. https://doi.org/10.1006/nimg.2002.1198
Ioan Opris, Manuel Casanova (2014) Prefrontal cortical minicolumn: from executive control to disrupted cognitive processing. 137(7), 1863-1875. https://doi.org/10.1093/brain/awt359
R. Barkley (2012) Executive functions: What are they, how they work, and why they evolved.
P. Redgrave, N. Vautrelle, J. Reynolds (2011) Functional properties of the basal ganglia's re-entrant loop architecture: selection and reinforcement. 198(3), 138-151. https://doi.org/10.1016/j.neuroscience.2011.07.060
Rubia Fusar-Poli P, et. Rossi G (2012) Striatal Dopamine Transporter Alterations in ADHD: Pathophysiology or Adaptation to Psychostimulants? A Meta-Analysis. 169(3), 264-272. https://doi.org/10.1176/appi.ajp.2011.11060940
Mrzljak L, Bergson C, Pappy M (1996) Localization of dopamine D4 receptors in GABAergic neurons of the primate brain. 381(6579), 245-248. https://doi.org/10.1038/381245a0
Yuen EY, Yan Z (2011) Cellular Mechanisms for Dopamine D4 Receptor-induced Homeostatic Regulation of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors. 286(28).
Nikolidas A, Gray JR (2010) ADHD and the DRD4 exon III 7-repeat polymorphism: an international meta-analysis. 5(2-3).
Das M, Das A, Bhaduri N (2011) Role of gene-gene/gene-environment interaction in the etiology of eastern Indian ADHD probands. 35(2), 577-587. https://doi.org/10.1016/j.pnpbp.2010.12.027
Durston S, Fossella JA, Casey BJ (2005) Differential effects of DRD4 and DAT1 genotype on fronto-striatal gray matter volumes in a sample of subjects with attention deficit hyperactivity disorder, their unaffected siblings, and controls. 10(7), 678-685. https://doi.org/10.1038/sj.mp.4001649
Fossella J, Sommer T, Fan J (2002) Assessing the molecular genetics of attention networks. 3(1), 14. https://doi.org/10.1186/1471-2202-3-14
Conners CK, Parker JDA, Sitarenios G (1998) The Revised Conners' Parent Rating Scale (CPRS-R): Factor Structure, Reliability, and Criterion Validity. 26(4), 257-268. https://doi.org/10.1023/a:1022602400621
D. Wechsler, Wechsler (1991) Intelligence Scale for Children-Third Edition: Manual.
Bharat J (1971) AIISH norms on SFB with Indian children. 2, 34-39.
S. Miller, D. Dykes, H. Polesky (1998) A simple salting out procedure for extracting DNA from human nucleated cells. 16(3), 1215-1215. https://doi.org/10.1093/nar/16.3.1215
Frank Dudbridge (2003) Pedigree disequilibrium tests for multilocus haplotypes. 25(2), 115-121. https://doi.org/10.1002/gepi.10252
R. Lenth (2007) Statistical power calculations1. 85(suppl_13), E24-E29. https://doi.org/10.2527/jas.2006-449
Barrett JC, Fry B, Maller J (2005) Haploview: analysis and visualization of LD and haplotype maps. 21(2), 263-265. https://doi.org/10.1093/bioinformatics/bth457
Jason Moore, Bill White (2007) Tuning ReliefF for Genome-Wide Genetic Analysis. 4447, 166-175. https://doi.org/10.1007/978-3-540-71783-6_16
Baker-Ericzen Li Y, et. Ji N (2013) Do SNPs of DRD4 gene predict adult persistence of ADHD in a Chinese sample?. 205(1-2), 143-50.
Sarkar Maitra S, P. Ghosh, et.al (2014) Potential Contribution of Dopaminergic Gene Variants in ADHD Core Traits and Co-Morbidity: A Study on Eastern Indian Probands. 34(4).
Nemoda Z, Lyons-Ruth K, Szekely A (2010) Association between dopaminergic polymorphisms and borderline personality traits among at-risk young adults and psychiatric inpatients. 6(1), 4. https://doi.org/10.1186/1744-9081-6-4
Demetrovics Vereczkei A, et. Szekely A (2013) Multivariate Analysis of Dopaminergic Gene Variants as Risk Factors of Heroin Dependence. 8(6), e66592. https://doi.org/10.1371/journal.pone.0066592
Lowe N, Kirley A, Mullins C (2004) Multiple marker analysis at the promoter region of the DRD4 gene and ADHD: Evidence of linkage and association with the SNP −616. 131, 33-37.
Okuyama Y, Ishiguro H, Toru M (1999) A Genetic Polymorphism in the Promoter Region of DRD4 Associated with Expression and Schizophrenia. 258(2), 292-295. https://doi.org/10.1006/bbrc.1999.0630
E. Kereszturi, O. Király, Z. Csapó (2007) Analysis of the dopamine D4 receptor gene variants in attention deficit hyperactivity disorder. 9(1).
A. Das Bhowmik, K. Sarkar, P. Ghosh (2013) Significance of dopaminergic gene variants in the male biasness of Attention Deficit Hyperactivity Disorder. https://doi.org/10.1177/1087054713494004.2013
Hattori Nakajima M, et. Yamada K (2007) Association and synergistic interaction between promoter variants of the DRD4 gene in Japanese schizophrenics. 52(1), 86-91. https://doi.org/10.1007/s10038-006-0084-3
J. Narbona-Garcia, R. Sanchez-Carpintero (1999) Neurobiology of attention deficit-hyperactivity disorder.
J. Lazar, Yitzchak Frank (1998) Frontal Systems Dysfunction in Children With Attention-Deficit/Hyperactivity Disorder and Learning Disabilities. 10(2), 160-167. https://doi.org/10.1176/jnp.10.2.160
Published
2016-08-30
Issue
Section
License
Copyright (c) 2016 Authors and Global Journals Private Limited

This work is licensed under a Creative Commons Attribution 4.0 International License.