Attention deficit disorders: Are we barking up the wrong tree?

Attention deficit disorder (AAD) and attention deficit/hyperactivity disorder (ADHD) are very frequent and protean developmental disorders without a definite biologic marker. This review proposes a framework to understand the enlarged spectrum of its manifestations based on current knowledge of the mechanisms underlying arousal and attention variations during sleep/wake cycle. The neuro-modulation's pivotal role in this process as well as in the fine tuning of synaptic architecture during development must be taken into account when trying to understand the marked fuzziness of the symptoms and the very high prevalence of reported co-morbidities. The series of related interactions includes a cyclic deactivation of the dorso-lateral portion of the prefrontal cortex (DLPFC) during sleep, suspending executive functions, co-occurring with rhythmic periods of decreased noradrenergic tonus. A protracted unbalance in modulation, with catecholaminergic relative deficiency, could explain less-than-optimum waking DLPFC activation and the most important manifestations of ADD. Beside the well documented dopaminergic effects of stimulant medication used in ADD and ADHD, a more important role must be assigned to noradrenaline (NA). At this light hyperactivity and impulsivity are less important dimensions. Rather, an attention deficit spectrum disorder should probably be regarded as a complication of a core defect in prefrontal cortex dependent inhibitory control, underlying inattention.