Hostname: page-component-7bb8b95d7b-cx56b Total loading time: 0 Render date: 2024-10-07T09:13:37.707Z Has data issue: false hasContentIssue false

Neurobiological Models of Attention-Deficit/Hyperactivity Disorder: A Brief Review of the Empirical Evidence

Published online by Cambridge University Press:  07 November 2014

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a psychiatric disorder characterized by inattention, impulsivity, and overactivity that begins in childhood. While considerable research has focused on the neurobiological substrates of this disorder, the specific nature of the brain dysfunction in ADHD has remained elusive. However, early data from pharmacological treatment studies, as well as from basic research in animals and humans, initially led several investigators to develop neurobiological models of ADHD. These models of ADHD and more recent evidence from neuropsychological, neuroimaging, neurochemical, and genetic research are briefly reviewed. While not completely consistent, the empirical data suggest that dysfunction in prefrontal-striatal neural circuits, as well as in brain stem catecholamine systems that innervate these circuits, may underlie the executive function deficits in ADHD.

Type
Feature Article
Copyright
Copyright © Cambridge University Press 2000

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1.Zametkin, AJ, Rapoport, JL. Neurobiology of attention deficit disorder with hyperactivity: where have we come in 50 years? J Am Acad Child Adolesc Psychiatry. 1987;26:676686.CrossRefGoogle Scholar
2.Barkley, RA, Grodzinsky, G, DuPaul, GJ. Frontal lobe functions in attention deficit disorder with and without hyperactivity: a review and research report. J Abnorm Child Psychol. 1992;20:163188.CrossRefGoogle ScholarPubMed
3.Filipek, PA. Neuroimaging in the developmental disorders: the state of the science. J Child Psychol Psychiatry. 1999;40:113128.CrossRefGoogle ScholarPubMed
4.Paterson, AD, Sunohara, GA, Kennedy, JL. Dopamine D4 receptor gene: novelty or nonsense? Neuropsychopharmacology. 1999;21:36.CrossRefGoogle ScholarPubMed
5.Heilman, KM, Voeller, KKS, Nadeau, SE. A possible pathophysiologic substrate of attention deficit hyperactivity disorder. J Child Neurol. 1991;6(suppl):S74S79.CrossRefGoogle ScholarPubMed
6.Pliszka, SR, McCracken, JT, Maas, JW. Catecholamines in attention-deficit hyperactivity disorder: current perspectives. J Am Acad Child Adolesc Psychiatry. 1996;35:264272.CrossRefGoogle ScholarPubMed
7.Arnsten, AFT, Steere, JC, Hunt, RD. The contribution of α2 noradrenergic mechanisms to prefrontal cognitive functions: potential significance to attention-deficit hyperactivity disorder. Arch Gen Psychiatry. 1996;53:448455.CrossRefGoogle Scholar
8.Corkum, PV, Siegel, LS. Is the continuous performance test a valuable research tool for use with children with attention-deficit hyperactivity disorder? J Child Psychol Psychiatry. 1993;34:12171239.CrossRefGoogle Scholar
9.Sternberg, S. Discovery of processing stages: extension of Donderas method. In: Koster, WG, ed. Attention and Performance. 2nd ed. Amsterdam, Netherlands: North Holland; 1969:276315.Google Scholar
10.van der Meere, JJ, Sergeant, J. Controlled processing and vigilance in hyperactivity: time will tell. J Abnorm Child Psychol. 1988;16:641656.CrossRefGoogle ScholarPubMed
11.van der Meere, JJ. The role of attention. In: Sandberg, S, ed. Monographs on Child and Adolescent Psychiatry: Hyperactivity Disorders. Cambridge, UK: Cambridge University Press; 1996;106145.Google Scholar
12.Barkley, RA. Behavioral inhibition, sustained attention, and executive functions: constructing a unifying theory of ADHD. Psychol Bull. 1997;121:6594.CrossRefGoogle ScholarPubMed
13.August, GJ, Garfinkel, BD. Behavioral and cognitive subtypes of ADHD. J Am Acad Child Adolesc Psychiatry. 1989;28:739748.CrossRefGoogle ScholarPubMed
14.Robins, PM. A comparison of behavioral and attentional functioning in children diagnosed as hyperactive or learning disabled. J Abnorm Child Psychol. 1992;20:6582.CrossRefGoogle ScholarPubMed
15.Pennington, BF, Groisser, D, Welsh, MC. Contrasting cognitive deficits in attention deficit hyperactivity disorder versus reading disability. Develop Psychol. 1993;29:511523.CrossRefGoogle Scholar
16.Hall, SJ, Halperin, JM, Schwartz, ST, et al.Behavioral and executive functions in children with attention-deficit hyperactivity disorder and reading disability. J Attention Disorders. 1997;1:235247.CrossRefGoogle Scholar
17.Purvis, KL, Tannock, R. Language abilities in children with attention deficit hyperactivity disorder, reading disabilities, and normal controls. J Abnorm Child Psychol. 1997;25:133144.CrossRefGoogle ScholarPubMed
18.Klorman, R, Hazel-Fernandez, LA, Shaywitz, SE, et al.Executive functioning deficits in attention-deficit/hyperactivity disorder are independent of oppositional defiant or reading disorder. J Am Acad Child Adolesc Psychiatry. 1999;38:11481155.CrossRefGoogle ScholarPubMed
19.Castellanos, FX, Giedd, JN, Marsh, WL, et al.Quantitative brain magnetic resonance imaging in attention-deficit hyperactivity disorder. Arch Gen Psychiatry. 1996;53:607616.CrossRefGoogle ScholarPubMed
20.Filipek, PA, Semrud-Clikeman, M, Steingard, RJ, et al.Volumetric MRI analysis comparing subjects having attention-deficit hyperactivity disorder with normal controls. Neurology. 1997;48:589601.CrossRefGoogle ScholarPubMed
21.Mostofsky, SH, Reiss, AL, Lockhart, P, et al.Evaluation of cerebellar size in attention-deficit hyperactivity disorder. J Child Neurol. 1998;13:434439.CrossRefGoogle ScholarPubMed
22.Hynd, GW, Semrud-Clikeman, M, Lorys, AR, Novey, ES, Eliopulos, D, Lyytinen, H. Corpus callosum morphology in attention deficit-hyperactivity disorder: morphometric analysis of MRI. J Learn Disabil. 1991;24:141146.CrossRefGoogle ScholarPubMed
23.Baving, L, Laucht, M, Schmidt, MH. Atypical frontal brain activation in ADHD: preschool and elementary school boys and girls. J Am Acad Child Adolesc Psychiatry. 1999;38:13631371.CrossRefGoogle ScholarPubMed
24.Chabot, RJ, Serfontein, G. Quantitative electroencephalographic profiles of children with attention deficit disorder. Biol Psychiatry. 1996;40:951963.CrossRefGoogle ScholarPubMed
25.Mann, CA, Lubar, JF, Zimmerman, AW, et al.Quantitative analysis of EEG in boys with attention-deficit-hyperactivity disorder: controlled study with clinical implications. Pediatr Neurol. 1992;8:3036.CrossRefGoogle ScholarPubMed
26.Matsuura, M, Okubo, Y, Toru, M, et al.A cross-national EEG study of children with emotional and behavioral problems: a WHO colloborative study in the Western Pacific Region. Biol Psychiatry. 1993;4:5965.CrossRefGoogle Scholar
27.Lou, HC, Henriksen, L, Bruhn, P. Striatal dysfunction in attention deficit and hyperkinetic disorder. Arch Neurol. 1989;46:4852.CrossRefGoogle ScholarPubMed
28.Amen, DG, Carmichael, BD. High-resolution brain SPECT imaging in ADHD. Ann Clin Psychiatry. 1997;9:8186.CrossRefGoogle ScholarPubMed
29.Zametkin, AJ, Nordahl, TE, Gross, M, et al.Cerebral glucose metabolism in adults with hyperactivity of childhood onset. N Engl J Med. 1990;323:13611366.CrossRefGoogle ScholarPubMed
30.Zametkin, AJ, Liebenauer, LL, Fitzgerald, GA, et al.Brain metabolism in teenagers with attention-deficit hyperactivity disorder. Arch Gen Psychiatry. 1993;50:333340.CrossRefGoogle ScholarPubMed
31.Vaidya, CJ, Austin, G, Kirkorian, G, et al.Selective effects of methylphenidate in attention deficit hyperactivity disorder: a functional magnetic resonance study. Proc Natl Acad Sci USA. 1998;95:1449414499.CrossRefGoogle ScholarPubMed
32.Rubia, K, Overmeyer, S, Taylor, E, et al.Hypofrontality in attention deficit hyperactivity disorder during higher-order motor control: a study with functional MRI. Am J Psychiatry. 1999;156:891896.CrossRefGoogle ScholarPubMed
33.Solanto, MV. Neuropsychopharmacological mechanisms of stimulant drug action in attention-deficit hyperactivity disorder: a review and integration. Behav Brain Res. 1998;94:127152.CrossRefGoogle ScholarPubMed
34.Halperin, JM, Newcorn, JH, Koda, VH, et al.Noradrenergic mechanisms in ADHD children with and without reading disabilities: a replication and extension. J Am Acad Child Adolesc Psychiatry. 1997;36:16881697.CrossRefGoogle ScholarPubMed
35.Castellanos, FX, Elia, J, Kruesi, MJ, et al.Cerebrospinal fluid homovanillic acid predicts behavioral response to stimulants in 45 boys with attention deficit/hyperactivity disorder. Neuropsychopharmacology. 1996;14:125137.CrossRefGoogle ScholarPubMed
36.Kruesi, MJ, Rapoport, JL, Hamburger, SD, et al.Cerebrospinal fluid monoamine metabolites, aggression, and impulsivity in disruptive behavior disorders of children and adolescents. Arch Gen Psychiatry. 1990;47:419426.CrossRefGoogle ScholarPubMed
37.Ernst, M, Zametkin, AJ, Matochik, JA, et al.DOPA decarboxylase activity in attention deficit hyperactivity disorder adults. A [fluorine-18]fluorodopa positron emission tomographic study. J Neurosci. 1998;18:59015907.CrossRefGoogle ScholarPubMed
38.Ernst, M, Zametkin, AJ, Matochil, JA, et al.High midbrain [,18F]DOPA accumulation in children with attention deficit hyperactivity disorder. Am J Psychiatry. 1999;156:12091215.CrossRefGoogle ScholarPubMed
39.Biederman, J, Faraone, S, Keenan, K, et al.Family-genetic and psychosocial risk factors in DSM-III attention deficit disorder. J Am Acad Child Adolesc Psychiatry. 1990;29:526533.CrossRefGoogle ScholarPubMed
40.Hechtman, L. Genetic and neurobiological aspects of attention deficit hyperactivity disorder: a review. J Psychiatry Neurosci. 1994:19:193201.Google ScholarPubMed
41.Comings, DE, Comings, BG, Muhleman, D, et al.The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders. JAMA. 1991;266:17931800.CrossRefGoogle ScholarPubMed
42.Swanson, JM, Sunohara, GA, Kennedy, JL, et al.Association of the dopamine receptor D4 (DRD4) gene with a refined phenotype of attention deficit hyperactivity disorder (ADHD): a family-based approach. Mol Psychiatry. 1998;3:3841.CrossRefGoogle Scholar
43.Faraone, SV, Biederman, J, Weiffenbach, B, et al.Dopamine D4 gene 7-repeat allele and attention deficit hyperactivity disorder. Am J Psychiatry. 1999;156:768770.CrossRefGoogle ScholarPubMed
44.Daly, G, Hawi, Z, Fitzgerald, M, et al.Mapping susceptibility loci in attention deficit hyperactivity disorder preferential transmission of parental alleles at DAT1, DBH and DRD5 to affected children. Mol Psychiatry. 1999;4:192196.CrossRefGoogle ScholarPubMed
45.Gill, M, Daly, G, Heron, S, Hawi, Z, et al.Confirmation of association between attention deficit disorder and a dopamine transporter polymorphism. Mol Psychiatry. 1997;2:311313.CrossRefGoogle Scholar
46.Winsberg, BG, Comings, DE. Association of the dopamine transporter gene (DAT1) with poor methylphenidate response. J Am Acad Child Adolesc Psychiatry. 1999;38:14741477.CrossRefGoogle ScholarPubMed
47.Goldman-Rakic, PS. Circuitry of the primate prefrontal cortex and the regulation of behavior by representational memory. In: Plum, F, ed. Handbook of Physiology, The Nervous System, Higher Functions of the Brain. Vol V. Bethesda, Md: American Physiological Society; 1987:373417.Google Scholar