A neuroanatomical and biochemical basis for attention deficit disorder with hyperactivity in children: a defect in tonic adrenaline mediated inhibition of locus coeruleus stimulation.

Attention deficit disorder with hyperactivity (ADDH) is characterized by a high level of inappropriate activity, distractability and impulsivity as well as learning deficits. In mammals, the protective mechanism for acquisition of sensory information, processed for its survival value, can be termed "vigilance". In ADDH, a low threshold for novel or sensory stimuli, results in a "hard wired" mammalian response, orienting, followed by exploratory behavior, the orienting reaction. This behavior is mediated in the brainstem through sensory neurons in the reticular formation regulating the discharge of locus coeruleus noradrenergic neurons. It is proposed that adrenaline acts as a tonic inhibitor of these neurons, modulating the level of sensory stimulation necessary to elicit locus coeruleus excitation. An imbalance in adrenaline formation or alpha-2 adrenergic receptor number (or affinity) leads to the inability to maintain the appropriate threshold for discharge of locus coeruleus neurons. The consequences are inability to maintain focused attention, difficulty in falling asleep or light levels of sleep, inattention to consumptive behavior, and probable inappropriate response for reward as all these behaviors require disruption of processing of sensory stimuli. Cognitive deficits may occur secondarily.