Etiologic Subtypes of Attention-Deficit/Hyperactivity Disorder: Brain Imaging, Molecular Genetic and Environmental Factors and the Dopamine Hypothesis |
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| Authors: | James M Swanson Marcel Kinsbourne Joel Nigg Bruce Lanphear Gerry A Stefanatos Nora Volkow Eric Taylor B J Casey F Xavier Castellanos Pathik D Wadhwa |
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| Institution: | (1) Department of Pediatrics, University of California, 19722 MacArthur Boulevard, Irvine, CA 92612, USA;(2) Department of Psychology, New School of Social Research, New York, NY, USA;(3) Department of Psychology, Michigan State University, East Lansing, Michigan, USA;(4) Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA;(5) Cognitive Neuropysiology Laoratory, Albert Einstein Medical Center, Philadelphia, PA, USA;(6) National Institute of Drug Abuse and Brookhaven National Laboratory, Rockville, Maryland, USA;(7) Department of Child Psychiatry, Institute for Psychiatry, London, UK;(8) Weill College of Medicine at Cornell University, Sackler Institute, New York, NY, USA;(9) Department of Child Psychiatry & Adolescent, New York University, New York, NY, USA;(10) Department of Psychiatry and OB/GYN, University of California, Irvine, California, USA |
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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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| Keywords: | ADHD (or Attention-Deficit/Hyperactivity Disorder) Dopamine Molecular genetics Brain imaging Environmental risk Minimal brain dysfunction |
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