title: Is attention-deficit/hyperactivity disorder an energy deficiency syndrome?
abstract: Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable yet clinically heterogeneous syndrome associated with hypocatecholamine function in subcortical and prefrontal cortical regions and clinical response to medications that enhance catecholamine function. The goal of this article is to present a hypothesis about the etiology of ADHD by synthesizing these findings with recent experiments indicating that activity-dependent neuronal energy consumption is regulated by cortical astrocytes. The scientific literature was searched from 1966 to the present using MEDLINE and relevant key words. Inattention and impulsivity may be related to hypofunctionality of catecholamine projection pathways to prefrontal cortical areas, resulting in decreased neuronal energy availability. This may be mediated by astrocyte catecholamine receptors that normally regulate energy availability during neuronal activation. At least some forms of ADHD may be viewed as cortical, energy-deficit syndromes secondary to catecholamine-mediated hypofunctionality of astrocyte glucose and glycogen metabolism, which provides activity-dependent energy to cortical neurons. Several tests of this hypothesis are proposed.
authors.affiliation: Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Todd
authors.forename: K N
authors.initials: KN
authors.lastname: Botteron
mesh_terms: D001253:Astrocytes / Q000378:metabolism; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis* / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism; D006008:Glycogen Storage Disease / Q000378:metabolism; D006801:Humans; D007773:Lactates / Q000378:metabolism; D009434:Neural Pathways / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism
chemical_list: D002395:Catecholamines; D007773:Lactates; D018698:Glutamic Acid; D000242:Cyclic AMP