Attention-Deficit/Hyperactivity Disorder Genomics: Update for Clinicians

被引:22
作者
Elia, Josephine [1 ]
Sackett, Jillan [2 ]
Turner, Terri [2 ]
Schardt, Martin [3 ]
Tang, Shih-Ching
Kurtz, Nicole [2 ]
Dunfey, Maura [2 ]
McFarlane, Nadia A. [2 ]
Susi, Aita [2 ]
Danish, David [2 ]
Li, Alice [2 ]
Nissley-Tsiopinis, Jenelle [2 ]
Borgmann-Winter, Karin [2 ]
机构
[1] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA
[2] Childrens Hosp Philadelphia, Ctr Sci, Dept Child & Adolescent Psychiat, Philadelphia, PA 19104 USA
[3] Trinity Coll, Hartford, CT 06106 USA
基金
美国国家卫生研究院;
关键词
Attention-deficit/hyperactivity disorder; ADHD; Genetics; Epigenetics; Structural variants; Copy number variation; Pharmacogenetics; ADHD comorbidity; Ethics/laws; DEFICIT HYPERACTIVITY DISORDER; OBSESSIVE-COMPULSIVE DISORDER; LONGITUDINAL GENETIC-ANALYSIS; MATERNAL SMOKING; ADHD-SYMPTOMS; ENVIRONMENTAL CONTRIBUTIONS; WIDE ASSOCIATION; METHYLPHENIDATE TREATMENT; PSYCHIATRIC-DISORDERS; ATOMOXETINE OVERDOSE;
D O I
10.1007/s11920-012-0309-4
中图分类号
R749 [精神病学];
学科分类号
100205 ;
摘要
Attention deficit, hyperactivity disorder (ADHD) is familial and highly heritable. Several candidate genes involved in neurotransmission have been identified, however these confer minimal risk, suggesting that for the most part, ADHD is not caused by single common genetic variants. Advances in genotyping enabling investigation at the level of the genome have led to the discovery of rare structural variants suggesting that ADHD is a genomic disorder, with potentially thousands of variants, and common neuronal pathways disrupted by numerous rare variants resulting in similar ADHD phenotypes. Heritability studies in humans also indicate the importance of epigenetic factors, and animal studies are deciphering some of the processes that confer risk during gestation and throughout the post-natal period. These and future discoveries will lead to improved diagnosis, individualized treatment, cures, and prevention. These advances also highlight ethical and legal issues requiring management and interpretation of genetic data and ensuring privacy and protection from misuse.
引用
收藏
页码:579 / 589
页数:11
相关论文
共 132 条
[1]   Short-term effects of adolescent methylphenidate exposure on brain striatal gene expression and sexual/endocrine parameters in male rats [J].
Adriani, Walter ;
Leo, Damiana ;
Guarino, Maria ;
Natoli, Alessia ;
Di Consiglio, Emma ;
De Angelis, Giovanna ;
Traina, Elsa ;
Testai, Emanuela ;
Perrone-Capano, Carla ;
Laviola, Giovanni .
CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE AND NEUROTOXICITY: COCAINE, GHB, AND SUBSTITUTED AMPHETAMINES, 2006, 1074 :52-73
[2]   The dopamine receptor D4 7-repeat allele influences neurocognitive functioning, but this effect is moderated by age and ADHD status: An exploratory study [J].
Altink, Marieke E. ;
Rommelse, Nanda N. J. ;
Slaats-Willemse, Dorine I. E. ;
Vasquez, Alejandro Arias ;
Franke, Barbara ;
Buschgens, Cathelijne J. M. ;
Fliers, Ellen A. ;
Faraone, Stephen V. ;
Sergeant, Joseph A. ;
Oosterlaan, Jaap ;
Buitelaar, Jan K. .
WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY, 2012, 13 (04) :293-305
[3]   Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2 [J].
Amir, RE ;
Van den Veyver, IB ;
Wan, M ;
Tran, CQ ;
Francke, U ;
Zoghbi, HY .
NATURE GENETICS, 1999, 23 (02) :185-188
[4]   The Child and Adolescent Twin Study in Sweden (CATSS) [J].
Anckarsater, Henrik ;
Lundstrom, Sebastian ;
Kollberg, Linnea ;
Kerekes, Nora ;
Palm, Camilla ;
Carlstrom, Eva ;
Langstrom, Niklas ;
Magnusson, Patrik K. E. ;
Halldner, Linda ;
Bolte, Sven ;
Gillberg, Christopher ;
Gumpert, Clara ;
Rastam, Maria ;
Lichtenstein, Paul .
TWIN RESEARCH AND HUMAN GENETICS, 2011, 14 (06) :495-508
[5]   Cdkn1c (p57Kip2) is the major regulator of embryonic growth within its imprinted domain on mouse distal chromosome 7 [J].
Andrews, Stuart C. ;
Wood, Michelle D. ;
Tunster, Simon J. ;
Barton, Sheila C. ;
Surani, M. Azim ;
John, Rosalind M. .
BMC DEVELOPMENTAL BIOLOGY, 2007, 7
[6]  
Archer T, 2011, J GENETIC SYNDROME G, V2
[7]   MODULATION OF INTRACELLULAR CYCLIC-AMP LEVELS BY DIFFERENT HUMAN DOPAMINE D4 RECEPTOR VARIANTS [J].
ASGHARI, V ;
SANYAL, S ;
BUCHWALDT, S ;
PATERSON, A ;
JOVANOVIC, V ;
VANTOL, HHM .
JOURNAL OF NEUROCHEMISTRY, 1995, 65 (03) :1157-1165
[8]   Mutations causing syndromic autism define an axis of synaptic pathophysiology [J].
Auerbach, Benjamin D. ;
Osterweil, Emily K. ;
Bear, Mark F. .
NATURE, 2011, 480 (7375) :63-U222
[9]  
Baird AL, 2011, MOL PSYCHIAT
[10]  
Barker MJ, 2004, VET HUM TOXICOL, V46, P130