View More View Less
  • 1 Department of Psychiatry and McKnight Brain Institute, University of Florida, College of Medicine, PO Box 103424, Gainesville, Florida, 32610-3424, USA
  • 2 Center for Psychiatric Medicine, North Andover, MA, USA
  • 3 Department of Clinical Medicine, Malibu Beach Recovery Center, Malibu Beach, CA, USA
  • 4 Department of Clinical Neurology, PATH Foundation NY, New York, NY, USA
  • 5 Community Mental Health Institute, Human Global Center for Clinical & Translational Science, University of Vermont, Burlington, VT, USA
  • 10 Department of Psychiatry, University of Vermont, College of Medicine, Burlington, VT, USA
  • 6 Dominion Diagnostics, Inc., North Kingstown, RI, USA
  • 7 Department of Personalized Medicine, IGENE, LLC, Austin, TX, USA
  • 8 University of Stellenbosch, Cape Town, South Africa
  • 9 Department of Management Science and Statistics, University of Texas at San Antonio, San Antonio, Texas, USA
Open access

Abstract

Background

Following the first association between the dopamine D2 receptor gene polymorphism and severe alcoholism, there has been an explosion of research reports in the psychiatric and behavioral addiction literature and neurogenetics. With this increased knowledge, the field has been rife with controversy. Moreover, with the advent of Whole Genome-Wide Studies (GWAS) and Whole Exome Sequencing (WES), along with Functional Genome Convergence, the multiple-candidate gene approach still has merit and is considered by many as the most prudent approach. However, it is the combination of these two approaches that will ultimately define real, genetic allelic relationships, in terms of both risk and etiology. Since 1996, our laboratory has coined the umbrella term Reward Deficiency Syndrome (RDS) to explain the common neurochemical and genetic mechanisms involved with both substance and non-substance, addictive behaviors.

Methods

This is a selective review of peer-reviewed papers primary listed in Pubmed and Medline.

Results

A review of the available evidence indicates the importance of dopaminergic pathways and resting-state, functional connectivity of brain reward circuits.

Discussion

Importantly, the proposal is that the real phenotype is RDS and impairments in the brain's reward cascade, either genetically or environmentally (epigenetically) induced, influence both substance and non-substance, addictive behaviors. Understanding shared common mechanisms will ultimately lead to better diagnosis, treatment and prevention of relapse. While, at this juncture, we cannot as yet state that we have “hatched the behavioral addiction egg”, we are beginning to ask the correct questions and through an intense global effort will hopefully find a way of “redeeming joy” and permitting homo sapiens live a life, free of addiction and pain.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • L. N. Al-Eitan S. A. Jaradat W. Qin D. M. Wildenauer D. D. Wildenauer G. K. Hulse G. K. Tay 2012 Characterization of serotonin transporter gene (SLC6A4) polymorphisms and its association with drug dependence in a Jordanian Arab population Toxicology and Industrial Health.

    • Search Google Scholar
    • Export Citation
  • J. Alsiö M. Rask-Andersen R. A. Chavan P. K. Olszewski A. S. Levine R. Fredriksson H. B. Schiöth 2014 Exposure to a high-fat high-sugar diet causes strong up-regulation of proopiomelanocortin and differentially affects dopamine D1 and D2 receptor gene expression in the brainstem of rats Neuroscience Letters 559 18 23.

    • Search Google Scholar
    • Export Citation
  • M. Anitha P. M. Abraham C. S. Paulose 2012 Striatal dopamine receptors modulate the expression of insulin receptor, IGF-1 and GLUT-3 in diabetic rats: Effect of pyridoxine treatment European Journal of Pharmacology 696 1–3 54 61.

    • Search Google Scholar
    • Export Citation
  • A. J. Ariza J. Hartman J. Grodecki A. Clavier K. Ghaey M. Elsner C. Moore O. O. Reina H. J. Binns 2013 Linking pediatric primary care obesity management to community programs Journal of Health Care for the Poor and Underserved 24 158 167.

    • Search Google Scholar
    • Export Citation
  • M. J. Bakermans-Kranenburg M. H. van Ijzendoorn 2011 Differential susceptibility to rearing environment depending on dopamine-related genes: New evidence and a meta-analysis Development and Psychopathology 23 1 39 52.

    • Search Google Scholar
    • Export Citation
  • D. T. Barratt J. K. Coller A. A. Somogyi 2006 Association between the DRD2 A1 allele and response to methadone and buprenorphine maintenance treatments American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 141B 4 323 331.

    • Search Google Scholar
    • Export Citation
  • K. M. Beaver J. Belsky 2012 Gene-environment interaction and the intergenerational transmission of parenting: Testing the differential-susceptibility hypothesis Psychiatric Quarterly 83 1 29 40.

    • Search Google Scholar
    • Export Citation
  • K. C. Berridge 2000 Measuring hedonic impact in animals and infants: Microstructure of affective taste reactivity patterns Neuroscience and Biobehavioral Reviews 24 2 173 198.

    • Search Google Scholar
    • Export Citation
  • B. B. Biswal J. van Kylen J. S. Hyde 1997 Simultaneous assessment of flow and BOLD signals in resting-state functional connectivity maps NMR in Biomedicine 10 4–5 165 170.

    • Search Google Scholar
    • Export Citation
  • K. Blum J. Bailey A. M. Gonzalez M. Oscar-Berman Y. Liu J. Giordano E. Braverman M. Gold 2011 Neuro-genetics of reward deficiency syndrome (RDS) as the root cause of “addiction transfer”: A new phenomenon common after bariatric surgery Journal of Genetic Syndromes and Gene Therapy 2012 1 S2 001.

    • Search Google Scholar
    • Export Citation
  • K. Blum A. L. Chen T. J. Chen P. Rhoades T. J. Prihoda B. W. Downs R. L. Waite L. Williams D. Braverman V. Arcuri M. Kerner S. H. Blum T. Palomo 2008 LG839: Anti-obesity effects and polymorphic gene correlates of reward deficiency syndrome Advances in Therapy 25 9 894 913.

    • Search Google Scholar
    • Export Citation
  • K. Blum A. L. Chen J. Giordano J. Borsten T. J. Chen M. Hauser T. Simpatico J. Femino E. R. Braverman D. Barh 2012 The addictive brain: All roads lead to dopamine Journal of Psychoactive Drugs 44 2 134 143.

    • Search Google Scholar
    • Export Citation
  • K. Blum T. J. H. Chen A. L. C. Chen P. Rhoades T. J. Prihoda B. W. Downs D. Bagchi M. Bagchi S. H. Blum L. Williams E. R. Braverman M. Kerner R. L. Waite B. Quirk L. White J. Reinking 2008 Dopamine D2 receptor Taq A1 allele predicts treatment compliance of LG839 in a subset analysis of pilot study in the Netherlands Genetic Therapy and Molecular Biology 12 129 140.

    • Search Google Scholar
    • Export Citation
  • K. Blum E. Gardner M. Oscar-Berman M. Gold 2012 “Liking” and “wanting” linked to Reward Deficiency Syndrome (RDS): Hypothesizing differential responsivity in brain reward circuitry Current Pharmaceutical Design 18 1 113 118.

    • Search Google Scholar
    • Export Citation
  • K. Blum E. P. Noble P. J. Sheridan A. Montgomery T. Ritchie P. Jagadeeswaran H. Nogami A. H. Briggs J. B. Cohn 1990 Allelic association of human dopamine D2 receptor gene in alcoholism JAMA 263 15 2055 2060.

    • Search Google Scholar
    • Export Citation
  • K. Blum M. Oscar-Berman R. D. Badgaiyan T. Palomo M. S. Gold 2014 Hypothesizing dopaminergic genetic antecedents in schizophrenia and substance seeking behavior Medical Hypotheses 82 5 606 614.

    • Search Google Scholar
    • Export Citation
  • K. Blum M. Oscar-Berman E. Stuller D. Miller J. Giordano S. Morse L. McCormick W. B. Downs R. L. Waite D. Barh D. Neal E. R. Braverman R. Lohmann J. Borsten M. Hauser D. Han Y. Liu M. Helman T. Simpatico 2012 Neurogenetics and nutrigenomics of neuro-nutrient therapy for Reward Deficiency Syndrome (RDS): Clinical ramifications as a function of molecular neurobiological mechanisms Journal of Addiction Research and Therapy 3 5 139.

    • Search Google Scholar
    • Export Citation
  • K. Blum P. J. Sheridan R. C. Wood E. R. Braverman T. J. Chen J. G. Cull D. E. Comings 1996 The D2 dopamine receptor gene as a determinant of reward deficiency syndrome Journal of the Royal Society of Medicine 89 7 396 400.

    • Search Google Scholar
    • Export Citation
  • K. D. Brownell 2012 Thinking forward: The quicksand of appeasing the food industry PLoS Medicine 9 7 e1001254.

  • J. D. Cameron M. E. Riou F. Tesson G. S. Goldfield R. Rabasa-Lhoret M. C. Brochu Doucet 2013 The TaqIA RFLP is associated with attenuated intervention-induced body weight loss and increased carbohydrate intake in post-menopausal obese women Appetite 60 1 111 116.

    • Search Google Scholar
    • Export Citation
  • C. L. Carpenter A. M. Wong Z. Li E. P. Noble D. Heber 2013 Association of dopamine D2 receptor and leptin receptor genes with clinically severe obesity Obesity (Silver Spring) 21 9 E467 473.

    • Search Google Scholar
    • Export Citation
  • K. C. Chen Y. C. Lin W. C. Chao H. K. Chung S. S. Chi W. S. Liu W. T. Wu 2012 Association of genetic polymorphisms of glutamate decarboxylase 2 and the dopamine D2 receptor with obesity in Taiwanese subjects Annals of Saudi Medicine 32 2 121 126.

    • Search Google Scholar
    • Export Citation
  • P. S. Chen Y. K. Yang T. L. Yeh I. H. Lee W. J. Yao N. T. Chiu R. B. Lu 2008 Correlation between body mass index and striatal dopamine transporter availability in healthy volunteers — a SPECT study Neuroimage 40 1 275 279.

    • Search Google Scholar
    • Export Citation
  • T. J. Chen K. Blum A. L. Chen A. Bowirrat W. B. Downs M. A. Madigan R. L. Waite J. A. Bailey M. Kerner S. Yeldandi N. Majmundar J. Giordano S. Morse D. Miller F. Fornari E. R. Braverman 2011 Neurogenetics and clinical evidence for the putative activation of the brain reward circuitry by a neuroadaptagen: Proposing an addiction candidate gene panel map Journal of Psychoactive Drugs 43 2 108 127.

    • Search Google Scholar
    • Export Citation
  • T. K. Clarke A. R. Weiss T. N. Ferarro K. M. Kampman C. A. Dackis H. M. Pettinati C. P. O'Brien D. W. Oslin F. W. Lohoff W. H. Berrettini 2014 The dopamine receptor D2 (DRD2) SNP rs1076560 is associated with opioid addiction Annals of Human Genetics 78 1 33 39.

    • Search Google Scholar
    • Export Citation
  • C. M. Colvis J. D. Pollock R. H. Goodman S. Impey J. Dunn G. Mandel F. A. Champagne M. Mayford E. Korzus A. Kumar W. Renthal D. E. H. Theobald E. J. Nestler 2005 Epigenetic mechanisms and gene networks in the nervous system The Journal of Neuroscience 25 45 10379 10389.

    • Search Google Scholar
    • Export Citation
  • J. P. Connor R. M. Young B. R. Lawford T. L. Ritchie E. P. Noble 2002 D(2) dopamine receptor (DRD2) polymorphism is associated with severity of alcohol dependence European Psychiatry 17 1 17 23.

    • Search Google Scholar
    • Export Citation
  • H. E. Creemers Z. Harakeh D. M. Dick J. Meyers W. A. Vollebergh J. Ormel F. C. Verhulst A. C. Huizink 2011 DRD2 and DRD4 in relation to regular alcohol and cannabis use among adolescents: Does parenting modify the impact of genetic vulnerability? The TRAILS study Drug and Alcohol Dependence 115 1–2 35 42.

    • Search Google Scholar
    • Export Citation
  • N. Danilovich L. D. Mastrandrea L. Cataldi T. Quattrin 2014 Methylphenidate decreases fat and carbohydrate intake in obese teenagers Obesity (Silver Spring) 22 3 781 785.

    • Search Google Scholar
    • Export Citation
  • Z. Demetrovics M. D. Griffiths 2012 Behavioral addictions: Past, present and future Journal of Behavioral Addictions 1 1 1 2.

  • J. P. Dunn R. L. Cowan N. D. Volkow I. D. Feurer R. Li D. B. Williams R. M. Kessler N. N. Abumrad 2010 Decreased dopamine type 2 receptor availability after bariatric surgery: Preliminary findings Brain Research 1350 123 130.

    • Search Google Scholar
    • Export Citation
  • S. A. Eisenstein J. A. Antenor-Dorsey D. M. Gredysa J. M. Koller E. C. Bihun S. A. Ranck A. M. Arbeláez S. Klein J. S. Perlmutter S. M. Moerlein K. J. Black T. Hershey 2013 A comparison of D2 receptor specific binding in obese and normal-weight individuals using PET with (N-[(11)C] methyl)benperidol Synapse 67 11 748 756.

    • Search Google Scholar
    • Export Citation
  • K. M. Eny P. N. Corey A. El-Sohemy 2009 Dopamine D2 receptor genotype (C957T) and habitual consumption of sugars in a free-living population of men and women Journal of Nutrigenetics and Nutrigenomics 2 4–5 235 242.

    • Search Google Scholar
    • Export Citation
  • L. H. Epstein R. A. Paluch J. N. Roemmich M. D. Beecher 2007 Family-based obesity treatment, then and now: Twenty-five years of pediatric obesity treatment Journal of Health Psychology 26 4 381 391.

    • Search Google Scholar
    • Export Citation
  • L. H. Epstein J. L. Temple B. J. Neaderhiser R. J. Salis R. W. Erbe J. J. Leddy 2007 Food reinforcement, the dopamine D2 receptor genotype, and energy intake in obese and nonobese humans Behavioral Neuroscience 121 5 877 886.

    • Search Google Scholar
    • Export Citation
  • Y. J. Fang G. N. Thomas Z. L. Xu J. Q. Fang J. A. Critchley B. Tomlinson 2005 An affected pedigree member analysis of linkage between the dopamine D2 receptor gene TaqI polymorphism and obesity and hypertension International Journal of Cardiology 102 1 111 116.

    • Search Google Scholar
    • Export Citation
  • B. F. Fuemmeler T. D. Agurs-Collins F. J. McClernon S. H. Kollins M. E. Kail A. W. Bergen A. E. Ashley-Koch 2008 Genes implicated in serotonergic and dopaminergic functioning predict BMI categories Obesity (Silver Spring) 16 2 348 355.

    • Search Google Scholar
    • Export Citation
  • M. S. Gold N. M. Avena 2013 Animal models lead the way to further understanding food addiction as well as providing evidence that drugs used successfully in addictions can be successful in treating overeating Biological Psychiatry 74 7 e11.

    • Search Google Scholar
    • Export Citation
  • M. S. Gold K. Blum M. Oscar-Berman E. R. Braverman 2014 Low dopamine function in attention deficit/hyperactivity disorder: Should genotyping signify early diagnosis in children? Postgraduate Medicine 126 153 177.

    • Search Google Scholar
    • Export Citation
  • A. Grzywacz J. Kucharska-Mazur J. Samochowiec 2008 Association studies of dopamine D4 receptor gene exon 3 in patients with alcohol dependence Psychiatria Polska 42 3 453 461.

    • Search Google Scholar
    • Export Citation
  • A. Gyollai M. D. Griffiths C. Barta A. Vereczkei R. Urban B. Kun G. Kokonyei A. Szekely M. Sasvari-Szekely K. Blum Z. Demetrovics 2014 The genetics of problem and pathological gambling: A systematic review Current Pharmaceutical Design 20 25 3993 3999.

    • Search Google Scholar
    • Export Citation
  • M. E. Hess S. Hess K. D. Meyer L. A. Verhagen L. Koch H. S. Brönneke M. O. Dietrich S. D. Jordan Y. Saletore O. Elemento B. F. Belgardt T. Franz T. L. Horvath U. Rüther S. R. Jaffrey P. Kloppenburg J. C. Brüning 2013 The fat mass and obesity associated gene (Fto) regulates activity of the dopaminergic midbrain circuitry Nature Neuroscience 16 8 1042 1048.

    • Search Google Scholar
    • Export Citation
  • J. A. Hettinger X. Liu M. L. Hudson A. Lee I. L. Cohen R. C. Michaelis C. E. Schwartz S. M. Lewis J. J. Holden 2012 DRD2 and PPP1R1B (DARPP-32) polymorphisms independently confer increased risk for autism spectrum disorders and additively predict affected status in male-only affected sib-pair families Behavioral and Brain Functions 8 19.

    • Search Google Scholar
    • Export Citation
  • A. Hone-Blanchet S. Fecteau 2014 Overlap of food addiction and substance use disorders definitions: Analysis of animal and human studies Neuropharmacology 85C 81 90.

    • Search Google Scholar
    • Export Citation
  • Q. F. Hou S. B. Li 2009 Potential association of DRD2 and DAT1 genetic variation with heroin dependence Neuroscience Letters 464 2 127 130.

    • Search Google Scholar
    • Export Citation
  • X. F. Huang Y. Yu K. Zavitsanou M. Han L. Storlien 2005 Differential expression of dopamine D2 and D4 receptor and tyrosine hydroxylase mRNAin mice prone, or resistant, to chronic high-fat diet-induced obesity Molecular Brain Research 135 1–2 150 161.

    • Search Google Scholar
    • Export Citation
  • E. Huertas G. Ponce M. A. Koeneke C. Poch L. Espana-Serrano T. Palomo M. A. Jiménez-Arriero J. Hoenicka 2010 The D2 dopamine receptor gene variant C957T affects human fear conditioning and aversive priming Genes, Brain and Behavior 9 1 103 109.

    • Search Google Scholar
    • Export Citation
  • M. Jablonski 2011 Genetic determinants of the alcohol dependence syndrome: Searching for an endophenotype associated with sweet liking in families with alcohol addiction Annales Academiae Medicae Stetinensis 57 1 79 87.

    • Search Google Scholar
    • Export Citation
  • M. M. Jacobs A. Okvist M. Horvath E. Keller M. J. Bannon S. Morgello Y. L. Hurd 2013 Dopamine receptor D1 and postsynaptic density gene variants associate with opiate abuse and striatal expression levels Molecular Psychiatry 18 11 1205 1210.

    • Search Google Scholar
    • Export Citation
  • D. Jutras-Aswad M. M. Jacobs G. Yiannoulos P. Roussos P. Bitsios Y. Nomura X. Liu Y. L. Hurd 2012 Cannabis-dependence risk relates to synergism between neuroticism and proenkephalin SNPs associated with amygdala gene expression: Case-control study PLoS One 7 6 e39243.

    • Search Google Scholar
    • Export Citation
  • R. M. Kessler D. H. Zald M. S. Ansari R. Li R. L. Cowan 2014 Changes in dopamine release and dopamine D2/3 receptor levels with the development of mild obesity Synapse 68 7 317 320.

    • Search Google Scholar
    • Export Citation
  • S. Y. Lee T. Y. Wang S. L. Chen S. Y. Huang N. S. Tzeng Y. H. Chang C. L. Wang Y. S. Wang I. H. Lee T. L. Yeh Y. K. Yang R. B. Lu 2013 Interaction between novelty seeking and the aldehyde dehydrogenase 2 gene in heroin-dependent patients Journal of Clinical Psychopharmacology 33 3 386 390.

    • Search Google Scholar
    • Export Citation
  • C.-Y. Li X. Mao L. Wei 2008 Genes and (common) pathways underlying drug addiction PLoS Computational Biology.

  • M. D. Li J. Z. Ma J. Beuten 2004 Progress in searching for susceptibility loci and genes for smoking-related behaviour Clinical Genetics 66 5 382 392.

    • Search Google Scholar
    • Export Citation
  • H. Lu E. A. Stein 2014 Resting state functional connectivity: Its physiological basis and application in neuropharmacology Neuropharmacology 84C 79 89.

    • Search Google Scholar
    • Export Citation
  • A. S. Masarik R. D. Conger M. B. Donnellan M. C. Stallings M. J. Martin T. J. Schofield T. K. Neppl L. V. Scaramelly A. Smolen K. F. Widaman 2014 For better and for worse: Genes and parenting interact to predict future behavior in romantic relationships Journal of Family Psychology 28 3 357 367.

    • Search Google Scholar
    • Export Citation
  • T. McLaughlin M. Oscar-Berman T. Simpatico J. Giordano S. Jones D. Barh W. B. Downs R. L. Waite M. Madigan K. Dushaj R. Lohmann E. R. Braverman D. Han K. Blum 2013 Hypothesizing repetitive paraphilia behavior of a medication refractive Tourette's syndrome patient having rapid clinical attenuation with KB220Z-nutrigenomic aminoacid therapy (NAAT) Journal of Behavioral Addictions 2 117 124.

    • Search Google Scholar
    • Export Citation
  • W. R. Mills-Koonce C. B. Propper J. L. Gariepy C. Blair P. Garrett-Peters M. J. Cox 2007 Bidirectional genetic and environmental influences on mother and child behavior: The family system as the unit of analyses Development and Psychopathology 19 4 1073 1087.

    • Search Google Scholar
    • Export Citation
  • M. R. Munafo I. J. Matheson J. Flint 2007 Association of the DRD2 gene Taq1A polymorphism and alcoholism: A meta-analysis of case-control studies and evidence of publication bias Molecular Psychiatry 12 5 454 461.

    • Search Google Scholar
    • Export Citation
  • A. C. Need K. R. Ahmadi T. D. Spector D. B. Goldstein 2006 Obesity is associated with genetic variants that alter dopamine availability Annals of Human Genetics 70 293 303.

    • Search Google Scholar
    • Export Citation
  • E. Nisoli A. Brunani E. Borgomainerio C. Tonello L. Dioni L. Briscini G. Redaelly E. Molinary F. Cavagnini M. O. Carruba 2007 D2 dopamine receptor (DRD2) gene Taq1A polymorphism and the eating-related psychological traits in eating disorders (anorexia nervosa and bulimia) and obesity Eating and Weight Disorders 12 2 91 96.

    • Search Google Scholar
    • Export Citation
  • E. P. Noble L. A. Gottschalk J. H. Fallon T. L. Ritchie J. C. Wu 1997 D2 dopamine receptor polymorphism and brain regional glucose metabolism American Journal of Medical Genetics 74 2 162 166.

    • Search Google Scholar
    • Export Citation
  • M. Ohmoto K. Sakaishi A. Hama A. Morita M. Nomura Y. Mitsumoto 2013 Association between dopamine receptor 2 TaqIA polymorphisms and smoking behavior with an influence of ethnicity: A systematic review and meta-analysis update Nicotine and Tobacco Research 15 3 633 642.

    • Search Google Scholar
    • Export Citation
  • C. N. Pato F. Macciardi M. T. Pato M. Verga J. L. Kennedy 1993 Review of the putative association of dopamine D2 receptor and alcoholism: A meta-analysis American Journal of Medical Genetics 48 2 78 82.

    • Search Google Scholar
    • Export Citation
  • M. Pecina B. J. Mickey T. Love H. Wang S. A. Langenecker C. Hodgkinson P. H. Shen S. Villafuerte D. Hsu S. L. Weisenbach C. S. Stohler D. Goldman J. K. Zubieta 2013 DRD2 polymorphisms modulate reward and emotion processing, dopamine neurotransmission and openness to experience Cortex 49 3 877 890.

    • Search Google Scholar
    • Export Citation
  • E. Pinto J. Reggers P. Gorwood C. Boni G. Scantamburlo W. Pitchot M. Ansseau 2009 The TaqI A DRD2 polymorphism in type II alcohol dependence: A marker of age at onset or of a familial disease? Alcohol 43 4 271 275.

    • Search Google Scholar
    • Export Citation
  • G. Ponce M. A. Jimenez-Arriero G. Rubio J. Hoenicka I. Ampuero J. A. Ramos T. Palomo 2003 The A1 allele of the DRD2 gene (TaqI A polymorphisms) is associated with antisocial personality in a sample of alcohol-dependent patients European Psychiatry 18 7 356 360.

    • Search Google Scholar
    • Export Citation
  • F. F. Roussotte N. Jahanshad D. P. Hibar P. M. Thompson Alzheimer's Disease Neuroimaging, I 2014 Altered regional brain volumes in elderly carriers of a risk variant for drug abuse in the dopamine D2 receptor gene (DRD2) Brain Imaging and Behavior.

    • Search Google Scholar
    • Export Citation
  • S. W. Savage D. H. Zald R. L. Cowan N. D. Volkow P. A. Marks-Shulman R. M. Kessler N. N. Abumrad J. P. Dunn 2014 Regulation of novelty seeking by midbrain dopamine D2/D3 signaling and ghrelin is altered in obesity Obesity (Silver Spring) 22 6 1452 1457.

    • Search Google Scholar
    • Export Citation
  • K. Schuck R. Otten R. C. Engels M. Kleinjan 2014 Initial responses to the first dose of nicotine in novel smokers: The role of exposure to environmental smoking and genetic predisposition Psychology and Health 29 6 698 716.

    • Search Google Scholar
    • Export Citation
  • N. R. Shah E. R. Braverman 2012 Measuring adiposity in patients: The utility of body mass index (BMI), percent body fat, and leptin PLoS One 7 4 e33308.

    • Search Google Scholar
    • Export Citation
  • M. Sikora A. Gese R. Czypicki M. Gasior A. Tretyn J. Chojnowski M. Bielimski M. Jaracz A. Kamimska R. Junik A. Borkowska 2013 Correlations between polymorphisms in genes coding elements of dopaminergic pathways and body mass index in overweight and obese women Endokrynologia Polska 64 2 101 107.

    • Search Google Scholar
    • Export Citation
  • L. Smith M. Watson S. Gates D. Ball D. Foxcroft 2008 Meta-analysis of the association of the Taq1A polymorphism with the risk of alcohol dependency: A HuGE gene-disease association review American Journal of Epidemiology 167 2 125 138.

    • Search Google Scholar
    • Export Citation
  • R. Spangler K. M. Wittkowski N. L. Goddard N. M. Avena B. G. Hoebel S. F. Leibowitz 2004 Opiate-like effects of sugar on gene expression in reward areas of the rat brain Molecular Brain Research 124 2 134 142.

    • Search Google Scholar
    • Export Citation
  • K. E. Steele G. P. Prokopowicz M. A. Schweitzer T. H. Magunsuon A. O. Lidor H. Kuwabawa A. Kumar J. Brasic D. F. Wong 2010 Alterations of central dopamine receptors before and after gastric bypass surgery Obesity Surgery 20 3 369 374.

    • Search Google Scholar
    • Export Citation
  • E. Stice A. Dagher 2010 Genetic variation in dopaminergic reward in humans Forum of Nutrition 63 176 185.

  • E. Stice K. Davis N. P. Miller C. N. Marti 2008 Fasting increases risk for onset of binge eating and bulimic pathology: A 5-year prospective study Journal of Abnormal Psychology 117 4 941 946.

    • Search Google Scholar
    • Export Citation
  • E. Stice S. Spoor C. Bohon D. M. Small 2008 Relation between obesity and blunted striatal response to food is moderated by TaqIA A1 allele Science 322 5900 449 452.

    • Search Google Scholar
    • Export Citation
  • E. Stice S. Spoor C. Bohon M. G. Veldhuizen D. M. Small 2008 Relation of reward from food intake and anticipated food intake to obesity: A functional magnetic resonance imaging study Journal of Abnormal Psychology 117 4 924 935.

    • Search Google Scholar
    • Export Citation
  • E. Stice S. Yokum K. Blum C. Bohon 2010 Weight gain is associated with reduced striatal response to palatable food The Journal of Neuroscience 30 39 13105 13109.

    • Search Google Scholar
    • Export Citation
  • E. Stice S. Yokum C. Bohon N. Marti A. Smolen 2010 Reward circuitry responsivity to food predicts future increases in body mass: Moderating effects of DRD2 and DRD4 Neuroimage 50 4 1618 1625.

    • Search Google Scholar
    • Export Citation
  • E. Stice S. Yokum K. Burger L. Epstein A. Smolen 2012 Multilocus genetic composite reflecting dopamine signaling capacity predicts reward circuitry responsivity The Journal of Neuroscience 32 29 10093 10100.

    • Search Google Scholar
    • Export Citation
  • E. Stice S. Yokum D. Zald A. Dagher 2011 Dopamine-based reward circuitry responsivity, genetics, and overeating Current Topics in Behavioral Neurosciences 6 81 93.

    • Search Google Scholar
    • Export Citation
  • D. Sullivan J. K. Pinsonneault A. C. Papp H. Zhu S. Lemeshow D. C. Mash W. Sadee 2013 Dopamine transporter DAT and receptor DRD2 variants affect risk of lethal cocaine abuse: A gene-gene-environment interaction Translational Psychiatry.

    • Search Google Scholar
    • Export Citation
  • H. Suraj Singh P. K. Ghosh K. N. Saraswathy 2013 DRD2 and ANKK1 gene polymorphisms and alcohol dependence: A case-control study among a Mendelian population of East Asian ancestry Alcohol and Alcoholism 48 4 409 414.

    • Search Google Scholar
    • Export Citation
  • G. Thomsen M. Ziebell P. S. Jensen S. da Cuhna-Bang G. M. Knudsen L. H. Pinborg 2013 No correlation between body mass index and striatal dopamine transporter availability in healthy volunteers using SPECT and [123I]PE2I Obesity (Silver Spring) 21 9 1803 1806.

    • Search Google Scholar
    • Export Citation
  • D. Tomasi N. D. Volkow 2013 Striatocortical pathway dysfunction in addiction and obesity: Differences and similarities Critical Reviews in Biochemsitry and Molecular Biology 48 1 1 19.

    • Search Google Scholar
    • Export Citation
  • P. Trifilieff B. Feng E. Urizar V. Winiger R. D. Ward K. M. Taylor D. Martinez H. Moore P. D. Balsam E. H. Simpson J. A. Javitch 2013 Increasing dopamine D2 receptor expression in the adult nucleus accumbens enhances motivation Molecular Psychiatry 18 9 1025 1033.

    • Search Google Scholar
    • Export Citation
  • H. Tsuchida I. Nishimura K. Fukui 2012 Alcohol and substance dependence Brain Nerve 64 2 163 173.

  • A. Valomon S. C. Holst V. Bachmann A. U. Viola C. Schmidt J. Zürcher W. Berger C. Cajochen H. P. Landolt 2014 Genetic polymorphisms of DAT1 and COMT differentially associate with actigraphy-derived sleep-wake cycles in young adults Chronobiology International 31 5 705 714.

    • Search Google Scholar
    • Export Citation
  • J. Vaske M. Makarios D. Boisvert K. M. Beaver J. P. Wright 2009 The interaction of DRD2 and violent victimization on depression: An analysis by gender and race Journal of Affective Disorders 112 1–3 120 125.

    • Search Google Scholar
    • Export Citation
  • A. Vereczkei Z. Demetrovics A. Szekely P. Sarkozy P. Antal A. Szilagyi M. Sasvari-Szekely C. Barta 2013 Multivariate analysis of dopaminergic gene variants as risk factors of heroin dependence PLoS One 8 6 e66592.

    • Search Google Scholar
    • Export Citation
  • N. D. Volkow G. J. Wang F. Telang J. S. Fowler R. Z. Goldstein N. Alia-Klein J. Logan C. Wong P. K. Thanos Y. Ma K. Pradhan 2009 Inverse association between BMI and prefrontal metabolic activity in healthy adults Obesity (Silver Spring) 17 1 60 65.

    • Search Google Scholar
    • Export Citation
  • D. Wang Y. Li S. G. Lee L. Wang J. Fan G. Zhang J. Wu Y. Ju S. Li 2011 Ethnic differences in body composition and obesity related risk factors: Study in Chinese and white males living in China PLoS One 6 5 e19835.

    • Search Google Scholar
    • Export Citation
  • F. Wang A. Simen A. Arias Q. W. Lu H. Zhang 2013 A large-scale meta-analysis of the association between the ANKK1/DRD2 Taq1A polymorphism and alcohol dependence Human Genetics 132 3 347 358.

    • Search Google Scholar
    • Export Citation
  • L. Wang X. Liu X. Luo M. Zeng L. Zuo K. S. Wang 2013 Genetic variants in the fat mass- and obesity-associated (FTO) gene are associated with alcohol dependence Journal of Molecular Neuroscience 51 2 416 424.

    • Search Google Scholar
    • Export Citation
  • T. Y. Wang S. Y. Lee S. L. Chen S. Y. Huang Y. H. Chang N. S. Tzeng C. L. Wang I. Hui Lee T. L. Yeh Y. K. Yang R. B. Lu 2013 Association between DRD2, 5-HTTLPR, and ALDH2 genes and specific personality traits in alcoholand opiate-dependent patients Behavioral Brain Research 250 285 292.

    • Search Google Scholar
    • Export Citation
  • A. J. Whitmer I. H. Gotlib 2012 Depressive rumination and the C957T polymorphism of the DRD2 gene Cognitive, Affective & Behavioral Neuroscience 12 4 741 747.

    • Search Google Scholar
    • Export Citation
  • I. Willuhn L. M. Burgeno P. A. Groblewski P. E. Phillips 2014 Excessive cocaine use results from decreased phasic dopamine signaling in the striatum Nature Neuroscience 17 5 704 709.

    • Search Google Scholar
    • Export Citation
  • J. K. Winkler A. Woehning J. H. Schultz M. Brune N. Beaton T. D. Challa S. Minkova E. Roeder P. P. Nawroth H. C. Friederich C. Wolfrum G. Rudofsky 2012 TaqIA polymorphism in dopamine D2 receptor gene complicates weight maintenance in younger obese patients Nutrition 28 10 996 1001.

    • Search Google Scholar
    • Export Citation
  • K. Xu D. Lichtermann R. H. Lipsky P. Franke X. Liu Y. Hu L. Cao S. G. Schwab D. B. Wildenauer C. H. Bau E. Ferro W. Astor T. Finch J. Terry J. Taubman W. Maier D. Goldman 2004 Association of specific haplotypes of D2 dopamine receptor gene with vulnerability to heroin dependence in 2 distinct populations Archives of General Psychiatry 61 6 597 606.

    • Search Google Scholar
    • Export Citation
  • R. M. Young B. R. Lawford A. Nutting E. P. Noble 2004 Advances in molecular genetics and the prevention and treatment of substance misuse: Implications of association studies of the A1 allele of the D2 dopamine receptor gene Addictive Behaviors 29 7 1275 1294.

    • Search Google Scholar
    • Export Citation
  • C. C. Zai S. Ehtesham E. Choi B. Nowrouzi V. de Luca L. Stankovich K. Davidge N. Freeman N. King J. L. Kennedy J. H. Beitchman 2012 Dopaminergic system genes in childhood aggression: Possible role for DRD2 The World Journal of Biological Psychiatry 13 1 65 74.

    • Search Google Scholar
    • Export Citation
  • L. Zhang L. Hu X. Li J. Zhang B. Chen 2014 The DRD2 rs1800497 polymorphism increase the risk of mood disorder: Evidence from an update meta-analysis Journal of Affective Disorders 158 71 77.

    • Search Google Scholar
    • Export Citation
  • Q. Zhu J. C. Shih 1997 An extensive repeat structure down-regulates human monoamine oxidase A promoter activity independent of an initiator-like sequence Journal of Neurochemistry 69 4 1368 1373.

    • Search Google Scholar
    • Export Citation
  • Y. F. Zou F. Wang X. L. Feng W. F. Li Y. H. Tian J. H. Tao F. M. Pan F. Huang 2012 Association of DRD2 gene polymorphisms with mood disorders: A meta-analysis Journal of Affective Disorders 136 3 229 237.

    • Search Google Scholar
    • Export Citation

Monthly Content Usage

Abstract Views Full Text Views PDF Downloads
Jun 2020 0 8 10
Jul 2020 17 2 5
Aug 2020 4 10 11
Sep 2020 0 23 30
Oct 2020 0 15 15
Nov 2020 0 24 19
Dec 2020 0 0 0