Abstract
This review revisits the thesis that a dysregulation of the central noradrenergic
networks may underlie the pathophysiology of ADHD. We review the pertinent neurobiological
and pharmacological literature on ADHD. The noradrenergic system has been intimately
associated with the modulation of higher cortical functions including attention, alertness,
vigilance and executive function. Noradrenergic activation is known to profoundly
affect the performance of attention, especially the maintenance of arousal, a cognitive
function known to be deficient in ADHD. Data from family, adoption, twin, and segregation
analysis strongly support a genetic hypothesis for this disorder. Although molecular
genetic studies of ADHD are relatively new and far from definitive, several replicated
reports have found associations between ADHD with DAT and D4 receptor genes. Brain
imaging studies fit well with the idea that dysfunction in fronto-subcortical pathways
occurs in ADHD with its underlying dysregulation of noradrenergic function. A wealth
of pharmacological data (within and without the stimulant literature) provides strong
evidence for selective clinical activity in ADHD for drugs with noradrenergic and
dopaminergic pharmacological profiles. Available research provides compelling theoretic,
basic biologic and clinical support for the notion that ADHD is a brain disorder of
likely genetic etiology with etiologic and pathophysiologic heterogeneity. Neurobiological
and pharmacological data provide compelling support for a noradrenergic hypothesis
of ADHD and suggest that drugs with noradrenergic activity may play an important role
in the therapeutics of this disorder.
Keywords
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Article info
Publication history
Accepted:
July 13,
1999
Received in revised form:
May 26,
1999
Received:
March 1,
1999
Identification
Copyright
© 1999 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
