Attention-deficit-hyperactivity disorder and reward deficiency syndrome

Kenneth Blum^1,6,7,8,9,10, Amanda Lih-Chuan Chen², Eric R Braverman^3,9, David E Comings⁴, Thomas JH Chen⁵, Vanessa Arcuri⁹, Seth H Blum⁶, Bernard W Downs^7,8, 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