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Attention-deficit-hyperactivity disorder and reward deficiency syndrome

Authors Blum K, Chen A, Braverman ER, Comings DE, Chen TJ, Arcuri V, Blum SH, Downs BW, Waite RL, Notaro A, Lubar J, Williams L, Prihoda TJ, Palomo T, Oscar-Berman MO

Published 10 October 2008 Volume 2008:4(5) Pages 893—917

DOI https://doi.org/10.2147/NDT.S2627

Kenneth Blum1,6,7,8,9,10, Amanda Lih-Chuan Chen2, Eric R Braverman3,9, David E Comings4, Thomas JH Chen5, Vanessa Arcuri9, Seth H Blum6, Bernard W Downs7,8, Roger L Waite7, Alison Notaro9, Joel Lubar10, Lonna Williams7, Thomas J Prihoda11, Tomas Palomo12, Marlene Oscar-Berman13

1Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC; 2Department of Engineering and Management of Advanced Technology, Chang Jung University, Tainan, Taiwan, Republic of China; 3Department of Neurosurgery, Weill College of Medicine, New York, NY; 4Department of Medical Genetics, City of Hope Medical Center, Duarte, CA; 5Department of Occupational Safety and Health, Chang Jung University, Tainan, Taiwan, Republic of China; 6Department of Psychoneurogenetics, Synapatamine, Inc., San Antonio, TX; 7LifeGen, Inc., La Jolla, CA; 8Allied Nutraceutical Research, Lederach, PA; 9PATH Research Foundation, New York, NY; 10Department of Physiology, University of Tennessee, Knoxville, TN; 11Department of Pathology, University of Texas Health Science Center, San Antonio, TX; 12Hospital Universitario 12 de Octubre, Madrid, Spain; 13Boston University School of Medicine, and Boston VA Healthcare System, Boston, MA

Parts of this manuscript have been published in Theor Biol Med Model (Comings et al 2005), which is an open access journal

Abstract: Molecular genetic studies have identified several genes that may mediate susceptibility to attention deficit hyperactivity disorder (ADHD). A consensus of the literature suggests that when there is a dysfunction in the “brain reward cascade,” especially in the dopamine system, causing a low or hypo-dopaminergic trait, the brain may require dopamine for individuals to avoid unpleasant feelings. This high-risk genetic trait leads to multiple drug-seeking behaviors, because the drugs activate release of dopamine, which can diminish abnormal cravings. Moreover, this genetic trait is due in part to a form of a gene (DRD2 A1 allele) that prevents the expression of the normal laying down of dopamine receptors in brain reward sites. This gene, and others involved in neurophysiological processing of specific neurotransmitters, have been associated with defi cient functions and predispose individuals to have a high risk for addictive, impulsive, and compulsive behavioral propensities. It has been proposed that genetic variants of dopaminergic genes and other “reward genes” are important common determinants of reward deficiency syndrome (RDS), which we hypothesize includes ADHD as a behavioral subtype. We further hypothesize that early diagnosis through genetic polymorphic identification in combination with DNA-based customized nutraceutical administration to young children may attenuate behavioral symptoms associated with ADHD. Moreover, it is concluded that dopamine and serotonin releasers might be useful therapeutic adjuncts for the treatment of other RDS behavioral subtypes, including addictions.

Keywords: attention deficit hyperactivity disorder (ADHD), genes, reward dependence, reward deficiency syndrome, treatment, neuropsychological deficits

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