The dopaminergic system in attention deficit/hyperactivity disorder.
Numerous studies have shown the importance of the mesocorticolimbic dopamine system in the pathophysiology of attention deficit/hyperactivity disorder. However, there has been inconsistency in the findings of those studies. Varied and sometimes contradictory interpretation has been made on the basis of similar results. It is, therefore, still unclear whether the dopaminergic system is hypo- or hyperfunctioning in attention deficit/hyperactivity disorder. The majority of the functional brain imaging studies in both clinical and experimental settings support hypofunction of the basal ganglia which receive abundant dopaminergic afferent. The experimental studies, using dopamine-depleted animals, also support the hypodopaminergic hypothesis, whereas recent studies with the dopamine transporter knockout/knockdown mouse suggest hyperdopaminergic function as the underlying abnormality. In this review we attempt to clarify the issues raised by previous neuroimaging and functional neuroimaging studies. Research involving animal models with genetic traits, genetic manipulation or with brain lesions is analysed, concentrating on the significance of the dopaminergic system in the abnormal behavior of attention deficit/hyperactivity disorder. In addition, the functional state of the dopaminergic system is considered through the speculated mechanism of psychostimulant therapy of the disorder. No final conclusions have been reached regarding the pathological, biochemical and physiological mechanisms responsible for various symptoms. Inconsistency in the findings and their interpretations may indicate the heterogeneity of the pathogenesis of this syndrome.
Ohno
Masaki
M
Department of Pediatrics, Shiga University of Medical Science, Otsu 520-2192, Japan. ohno@belle.shiga-med.ac.jp
D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D006801:Humans; D008279:Magnetic Resonance Imaging; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins; D016627:Oxidopamine / Q000378:metabolism; D011859:Radiography; D051381:Rats; D011954:Receptors, Dopamine / Q000378:metabolism*
D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011954:Receptors, Dopamine; D016627:Oxidopamine; D004298:Dopamine