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Biol Psychiatry. 1999 Nov 1;46(9):1234-42.

Attention-deficit/hyperactivity disorder (ADHD) as a noradrenergic disorder.

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Pediatric Psychopharmacology Unit, Massachusetts General Hospital, Boston 02114, USA.


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.

[Indexed for MEDLINE]

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