Cited by 580Attention Deficit Hyperactivity DisorderNeurotransmitter Receptor Influence on BehaviorNeural and Behavioral Psychology Studies

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Etiologic Subtypes of Attention-Deficit/Hyperactivity Disorder: Brain Imaging, Molecular Genetic and Environmental Factors and the Dopamine Hypothesis

Swanson, James M., Kinsbourne, Marcel, Nigg, Joel, Lanphear, Bruce, Stefanatos, Gerry A., Volkow, Nora, Taylor, Eric, Casey, B. J., Castellanos, F. Xavier, Wadhwa, Pathik D.·2007·Neuropsychology Review

DOI 10.1007/s11065-007-9019-9

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Abstract

Multiple theories of Attention-Deficit/Hyper-activity Disorder (ADHD) have been proposed, but one that has stood the test of time is the dopamine deficit theory. We review the narrow literature from recent brain imaging and molecular genetic studies that has improved our understanding of the role of dopamine in manifestation of symptoms of ADHD, performance deficits on neuropsychological tasks, and response to stimulant medication that constitutes the most common treatment of this disorder. First, we consider evidence of the presence of dopamine deficits based on the recent literature that (1) confirms abnormalities in dopamine-modulated frontal-striatal circuits, reflected by size (smaller-than-average components) and function (hypoactivation); (2) clarifies the agonist effects of stimulant medication on dopaminergic mechanisms at the synaptic and circuit level of analysis; and (3) challenges the most-widely accepted ADHD-related neural abnormality in the dopamine system (higher-than-normal dopamine transporter [DAT] density). Second, we discuss possible genetic etiologies of dopamine deficits based on recent molecular genetic literature, including (1) multiple replications that confirm the association of ADHD with candidate genes related to the dopamine receptor D4 (DRD4) and the DAT; (2) replication of differences in performance of neuropsychological tasks as a function of the DRD4 genotype; and (3) multiple genome-wide linkage scans that demonstrate the limitations of this method when applied to complex disorders but implicate additional genes that may contribute to the genetic basis of ADHD. Third, we review possible environmental etiologies of dopamine deficits based on recent studies of (1) toxic substances that may affect the dopamine system in early development and contribute substantially to the etiology of ADHD; (2) fetal adaptations in dopamine systems in response to stress that may alter early development with lasting effects, as proposed by the developmental origins of health and disease hypothesis; and (3) gene-environment interactions that may moderate selective damage or adaptation of dopamine neurons. Based on these reviews, we identify critical issues about etiologic subtypes of ADHD that may involve dopamine, discuss methods that could be used to address these issues, and review old and new theories that may direct research in this area in the future.

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Authors: Swanson, J. M., Kinsbourne, M., Nigg, J., Lanphear, B., Stefanatos, G. A., Volkow, N., Taylor, E., Casey, B. J., Castellanos, F. X., & Wadhwa, P. D.
Affiliations: University of California, Irvine (US)
The New School (US)
Michigan State University (US)
Cincinnati Children's Hospital Medical Center (US)
Jefferson Einstein Philadelphia Hospital (US)
Brookhaven National Laboratory (US)
Cornell University (US)
New York University (US)
Corresponding author: Swanson, James M.
ORCID: Swanson, James M.
Nigg, Joel
Lanphear, Bruce
Volkow, Nora
Casey, B. J.
Castellanos, F. Xavier
Wadhwa, Pathik D.
Venue: Neuropsychology Review
Publisher: Springer Science and Business Media LLC
Published: 2007-02-21
Volume: 17
Issue: 1
Pages: 39-59
ISSN: 1040-7308 (ISSN-L)
1573-6660
DOI: 10.1007/s11065-007-9019-9
OpenAlex: W2098273438
Cited by: 580
References: 165
Citations by year: 2026: 8 · 2025: 15 · 2024: 18 · 2023: 26 · 2022: 26 · 2021: 26 · 2020: 24 · 2019: 20 · 2018: 23 · 2017: 27 · 2016: 31 · 2015: 44 · 2014: 37 · 2013: 38 · 2012: 36
FWCI: 6.34
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Neuropsychology Review (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Keywords: attention deficit hyperactivity disorder, dopamine transporter, DRD4 gene, stimulant medication response, frontostriatal circuits, genome-wide linkage analysis, environmental etiology, developmental origins of health and disease, gene-environment interaction, prenatal stress, developmental neurotoxicity
MeSH terms: Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Brain, Brain Mapping, Dopamine, Humans, Molecular Biology, Nerve Tissue Proteins, Psychological Theory

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Etiologic Subtypes of Attention-Deficit/Hyperactivity Disorder: Brain Imaging, Molecular Genetic and Environmental Factors and the Dopamine Hypothesis

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