Molecular Genetics of Attention Deficit Hyperactivity Disorder

Overview

Journal Psychiatr Clin North Am

Specialty Psychiatry

Date 2010 Feb 18

PMID 20159345

Citations 123

Authors

Stephen V Faraone

Eric Mick

Affiliations

Soon will be listed here.

Abstract

Although twin studies demonstrate that ADHD is a highly heritable condition, molecular genetic studies suggest that the genetic architecture of ADHD is complex. The handful of genome-wide linkage and association scans that have been conducted thus far show divergent findings and are, therefore, not conclusive. Similarly, many of the candidate genes reviewed here (ie, DBH, MAOA, SLC6A2, TPH-2, SLC6A4, CHRNA4, GRIN2A) are theoretically compelling from neurobiological systems perspective but available data are sparse and inconsistent. However, candidate gene studies of ADHD have produced substantial evidence implicating several genes in the etiology of the disorder, with meta-analyses supportive of a role of the genes coding for DRD4, DRD5, SLC6A3, SNAP-25, and HTR1B in the etiology of ADHD.

Citing Articles

Is There a Deficit in Product and Process of Handwriting in Children with Attention Deficit Hyperactivity Disorder? A Systematic Review and Recommendations for Future Research.

Puyjarinet F, Chaix Y, Biotteau M Children (Basel). 2024; 11(1).

PMID: 38255345 PMC: 10813961. DOI: 10.3390/children11010031.

The A328 V/E (rs2887147) polymorphisms in human tryptophan hydroxylase 2 compromise enzyme activity.

Carkaci-Salli N, Bewley M, Tekin I, Flanagan J, Vrana K Biochem Biophys Rep. 2023; 35:101527.

PMID: 37608910 PMC: 10440358. DOI: 10.1016/j.bbrep.2023.101527.

Human microglia maturation is underpinned by specific gene regulatory networks.

Han C, Li R, Hansen E, Trescott S, Fixsen B, Nguyen C Immunity. 2023; 56(9):2152-2171.e13.

PMID: 37582369 PMC: 10529991. DOI: 10.1016/j.immuni.2023.07.016.

evaluation of the role of lisdexamfetamine on attention-deficit/hyperactivity disorder common psychiatric comorbidities: mechanistic insights on binge eating disorder and depression.

Gutierrez-Casares J, Segu-Verges C, Sabate Chueca J, Pozo-Rubio T, Coma M, Montoto C Front Neurosci. 2023; 17:1118253.

PMID: 37457000 PMC: 10347683. DOI: 10.3389/fnins.2023.1118253.

Children and adolescents with attention deficit hyperactivity disorder and autism spectrum disorder share distinct microbiota compositions.

Bundgaard-Nielsen C, Lauritsen M, Knudsen J, Rold L, Larsen M, Hindersson P Gut Microbes. 2023; 15(1):2211923.

PMID: 37199526 PMC: 10197996. DOI: 10.1080/19490976.2023.2211923.

References

Comings D, Wu S, Chiu C, Ring R, Gade R, Ahn C . Polygenic inheritance of Tourette syndrome, stuttering, attention deficit hyperactivity, conduct, and oppositional defiant disorder: the additive and subtractive effect of the three dopaminergic genes--DRD2, D beta H, and DAT1. Am J Med Genet. 1996; 67(3):264-88. DOI: 10.1002/(SICI)1096-8628(19960531)67:3<264::AID-AJMG4>3.0.CO;2-N. View

Domschke K, Sheehan K, Lowe N, Kirley A, Mullins C, OSullivan R . Association analysis of the monoamine oxidase A and B genes with attention deficit hyperactivity disorder (ADHD) in an Irish sample: preferential transmission of the MAO-A 941G allele to affected children. Am J Med Genet B Neuropsychiatr Genet. 2005; 134B(1):110-4. DOI: 10.1002/ajmg.b.30158. View

Tang G, Ren D, Xin R, Qian Y, Wang D, Jiang S . Lack of association between the tryptophan hydroxylase gene A218C polymorphism and attention-deficit hyperactivity disorder in Chinese Han population. Am J Med Genet. 2001; 105(6):485-8. DOI: 10.1002/ajmg.1471. View

Mill J, Curran S, Kent L, Gould A, Huckett L, Richards S . Association study of a SNAP-25 microsatellite and attention deficit hyperactivity disorder. Am J Med Genet. 2002; 114(3):269-71. DOI: 10.1002/ajmg.10253. View

Rowe D, van den Oord E, Stever C, Giedinghagen L, Gard J, Cleveland H . The DRD2 TaqI polymorphism and symptoms of attention deficit hyperactivity disorder. Mol Psychiatry. 1999; 4(6):580-6. DOI: 10.1038/sj.mp.4000567. View

Smoller J, Biederman J, Arbeitman L, Doyle A, Fagerness J, Perlis R . Association between the 5HT1B receptor gene (HTR1B) and the inattentive subtype of ADHD. Biol Psychiatry. 2005; 59(5):460-7. DOI: 10.1016/j.biopsych.2005.07.017. View

Faraone S, Perlis R, Doyle A, Smoller J, Goralnick J, Holmgren M . Molecular genetics of attention-deficit/hyperactivity disorder. Biol Psychiatry. 2005; 57(11):1313-23. DOI: 10.1016/j.biopsych.2004.11.024. View

Kim Y, Leventhal B, Kim S, Kim B, Cheon K, Yoo H . Family-based association study of DAT1 and DRD4 polymorphism in Korean children with ADHD. Neurosci Lett. 2005; 390(3):176-81. DOI: 10.1016/j.neulet.2005.08.025. View

Swanson J, Oosterlaan J, Murias M, Schuck S, Flodman P, Spence M . Attention deficit/hyperactivity disorder children with a 7-repeat allele of the dopamine receptor D4 gene have extreme behavior but normal performance on critical neuropsychological tests of attention. Proc Natl Acad Sci U S A. 2000; 97(9):4754-9. PMC: 18305. DOI: 10.1073/pnas.080070897. View

10.

Grady D, Harxhi A, Smith M, Flodman P, Spence M, Swanson J . Sequence variants of the DRD4 gene in autism: further evidence that rare DRD4 7R haplotypes are ADHD specific. Am J Med Genet B Neuropsychiatr Genet. 2005; 136B(1):33-5. DOI: 10.1002/ajmg.b.30182. View

11.

Turic D, Langley K, Mills S, Stephens M, Lawson D, Govan C . Follow-up of genetic linkage findings on chromosome 16p13: evidence of association of N-methyl-D aspartate glutamate receptor 2A gene polymorphism with ADHD. Mol Psychiatry. 2004; 9(2):169-73. DOI: 10.1038/sj.mp.4001387. View

12.

Lasky-Su J, Anney R, Neale B, Franke B, Zhou K, Maller J . Genome-wide association scan of the time to onset of attention deficit hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet. 2008; 147B(8):1355-8. PMC: 2605611. DOI: 10.1002/ajmg.b.30869. View

13.

Cases O, Lebrand C, Giros B, Vitalis T, De Maeyer E, Caron M . Plasma membrane transporters of serotonin, dopamine, and norepinephrine mediate serotonin accumulation in atypical locations in the developing brain of monoamine oxidase A knock-outs. J Neurosci. 1998; 18(17):6914-27. PMC: 6792975. View

14.

DasBanerjee T, Middleton F, Berger D, Lombardo J, Sagvolden T, Faraone S . A comparison of molecular alterations in environmental and genetic rat models of ADHD: a pilot study. Am J Med Genet B Neuropsychiatr Genet. 2008; 147B(8):1554-63. PMC: 2587509. DOI: 10.1002/ajmg.b.30877. View

15.

Hebebrand J, Dempfle A, Saar K, Thiele H, Herpertz-Dahlmann B, Linder M . A genome-wide scan for attention-deficit/hyperactivity disorder in 155 German sib-pairs. Mol Psychiatry. 2005; 11(2):196-205. DOI: 10.1038/sj.mp.4001761. View

16.

Bhaduri N, Mukhopadhyay K . Lack of significant association between -1021C-->T polymorphism in the dopamine beta hydroxylase gene and attention deficit hyperactivity disorder. Neurosci Lett. 2006; 402(1-2):12-6. DOI: 10.1016/j.neulet.2006.03.036. View

17.

El-Faddagh M, Laucht M, Maras A, Vohringer L, Schmidt M . Association of dopamine D4 receptor (DRD4) gene with attention-deficit/hyperactivity disorder (ADHD) in a high-risk community sample: a longitudinal study from birth to 11 years of age. J Neural Transm (Vienna). 2004; 111(7):883-9. DOI: 10.1007/s00702-003-0054-2. View

18.

Kirley A, Hawi Z, Daly G, McCarron M, Mullins C, Millar N . Dopaminergic system genes in ADHD: toward a biological hypothesis. Neuropsychopharmacology. 2002; 27(4):607-19. DOI: 10.1016/S0893-133X(02)00315-9. View

19.

Sheehan K, Lowe N, Kirley A, Mullins C, Fitzgerald M, Gill M . Tryptophan hydroxylase 2 (TPH2) gene variants associated with ADHD. Mol Psychiatry. 2005; 10(10):944-9. DOI: 10.1038/sj.mp.4001698. View

20.

Jiang S, Xin R, Lin S, Qian Y, Tang G, Wang D . Linkage studies between attention-deficit hyperactivity disorder and the monoamine oxidase genes. Am J Med Genet. 2002; 105(8):783-8. DOI: 10.1002/ajmg.10098. View