Abstract
We have entered the genomics era with hope for the future of medicine including psychiatry. Understanding the role of DNA and polymorphic associations with brain reward circuitry has led to a new understanding of all addictive behaviors. We present here a brief review of the role of both neurogenetics and nutrigenomics as cornerstones that link more accurate genetic diagnosis and dopamine D2 agonist therapy to induce dopaminergic activation. Based on numerous experiments we are indeed proposing a novel approach. We challenge the entire recovery field to use these tools, the result of years of scientific research into the nature of addiction, and to incorporate them into treatment programs for patients attending inpatient/outpatient addiction clinics, such as the Genetic Addiction Risk Score (GARS)™ for appropriate RDS diagnosis, Comprehensive Analysis of Reported Drugs (CARD)™ to determine both compliance and abstinence during treatment, natural D2 agonistic therapy (NAAT-KB220™), and, eventually, mRNA (patent pending) to determine pre- and post-candidate gene expressions in reward deficiency syndrome (RDS). We are, therefore, proposing a paradigm shift we have called “Reward Deficiency Solutions System (RDSS)™.”
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References
Alia-Klein N, Parvaz MA, Woicik PA, Konova AB, Maloney T, Shumay E, Wang R, Telang F, Biegon A, Wang GJ, Fowler JS, Tomasi D, Volkow ND, Goldstein RZ (2011) Gene × disease interaction on orbitofrontal gray matter in cocaine addiction. Arch Gen Psychiatry 68(3):283–294
Baransel Isir AB, Oguzkan S, Nacak M, Gorucu S, Dulger HE, Arslan A (2008) The catechol-O-methyl transferase Val158Met polymorphism and susceptibility to cannabis dependence. Am J Forensic Med Pathol 29(4):320–322
Barr CL, Kidd KK (1993) Population frequencies of the A1 allele at the dopamine D2 receptor locus. Biol Psychiatry 34(4):204–209
Bart G, Kreek MJ, Ott J, LaForge KS, Proudnikov D, Pollak L, Heilig M (2005) Increased attributable risk related to a functional mu-opioid receptor gene polymorphism in association with alcohol dependence in central Sweden. Neuropsychopharmacology 30(2):417–422
Biederman J, Petty CR, Ten Haagen KS, Small J, Doyle AE, Spencer T, Mick E, Monuteaux MC, Smoller JW, Faraone SV (2009) Effect of candidate gene polymorphisms on the course of attention deficit hyperactivity disorder. Psychiatry Res 170(2–3):199–203
Blum K, Gold MS (2011) Neuro-chemical activation of brain reward mesolimbic circuitry is associated with relapse prevention and drug hunger: a hypothesis. Med Hypotheses 76(4):576–584
Blum K, Kozlowski GP (1990) Ethanol and neuromodulators interaction: a cascade model of reward. In: Ollat H, Parvez S, Parvez H (eds) Alcohol and behavior. VSP Press, Utrecht
Blum K, Wallace JE (1974) Effects of catecholamine synthesis inhibition on ethanol-induced withdrawal symptoms in mice. Br J Pharmacol 51(1):109–111
Blum K, Briggs AH, Trachtenberg MC, Delallo L, Wallace JE (1987) Enkephalinase inhibition: regulation of ethanol intake in genetically predisposed mice. Alcohol 4(6):449–456
Blum K, Calhoun W, Wallace JE, Merritt JH, Geller I (1973) Soporific action of ethanol in mice: possible role of biogenic amines. Pharmacol Biochem Behav 1(3):271–276
Blum K, Trachtenberg MC, Elliott CE, Dingler ML, Sexton RL, Samuels AI, Cataldie L (1988) Enkephalinase inhibition and precursor amino acid loading improves inpatient treatment of alcohol and polydrug abusers: double-blind placebo-controlled study of the nutritional adjunct SAAVE. Alcohol 5(6):481–493
Blum K, Noble EP, Sheridan PJ, Montgomery A, Ritchie T, Jagadeeswaran P, Nogami H, Briggs AH, Cohn JB (1990) Allelic association of human dopamine D2 receptor gene in alcoholism. JAMA 263(15):2055–2060
Blum K, Sheridan PJ, Wood RC, Braverman ER, Chen TJ, Comings DE (1995a) Dopamine D2 receptor gene variants: association and linkage studies in impulsive-addictive-compulsive behavior. Pharmacogenetics 5(3):121–141
Blum K, Wood RC, Braverman ER, Chen TJ, Sheridan PJ (1995b) The D2 dopamine receptor gene as a predictor of compulsive disease: Bayes’ theorem. Funct Neurol 10(1):37–44
Blum K, Braverman ER, Wood RC, Gill J, Li C, Chen TJ, Taub M, Montgomery AR, Sheridan PJ, Cull JG (1996a) Increased prevalence of the Taq I A1 allele of the dopamine receptor gene (DRD2) in obesity with comorbid substance use disorder: a preliminary report. Pharmacogenetics 6(4):297–305
Blum K, Sheridan PJ, Wood RC, Braverman ER, Chen TJ, Cull JG, Comings DE (1996b) The D2 dopamine receptor gene as a determinant of reward deficiency syndrome. J R Soc Med 89(7):396–400
Blum K, Braverman ER, Wu S, Cull JG, Chen TJ, Gill J, Wood R, Eisenberg A, Sherman M, Davis KR, Matthews D, Fischer L, Schnautz N, Walsh W, Pontius AA, Zedar M, Kaats G, Comings DE (1997) Association of polymorphisms of dopamine D2 receptor (DRD2), and dopamine transporter (DAT1) genes with schizoid/avoidant behaviors (SAB). Mol Psychiatry 2(3):239–246
Blum K, Chen TJ, Meshkin B, Downs BW, Gordon CA, Blum S, Mengucci JF, Braverman ER, Arcuri V, Varshavskiy M, Deutsch R, Martinez-Pons M (2006) Reward deficiency syndrome in obesity: a preliminary cross-sectional trial with a Genotrim variant. Adv Ther 23(6):1040–1051
Blum K, Chen TJH, Downs BW, Meshkin B, Blum SH et al (2007) Synaptamine (SG8839)™, an amino-acid enkephalinase inhibition nutraceutical improves recovery of alcoholics, a subtype of reward deficiency syndrome (RDS). Trends Appl Sci Res 2:132–138
Blum K, Chen AL, Chen TJ, Rhoades P, Prihoda TJ, Downs BW, Waite RL, Williams L, Braverman ER, Braverman D, Arcuri V, Kerner M, Blum SH, Palomo T (2008a) LG839: anti-obesity effects and polymorphic gene correlates of reward deficiency syndrome. Adv Ther 25(9):894–913
Blum K, Chen ALC, Chen TJH, Braverman ER, Reinking J, Blum SH, Cassel K, Downs BW, Waite L, Williams L, Prihoda TJ, Kerner MM, Palomo T, Comings DE, Tung H, Rhoades P, Oscar-Berman M (2008b) Activation instead of blocking mesolimbic dopaminergic reward circuitry is a preferred modality in the long term treatment of reward deficiency syndrome (RDS): a commentary. Theor Biol Med Model 5:24. doi:10.1186/1742-4682-5-24
Blum K, Chen TH, Chen ALC, Rhoades P, Prihoda TJ, Downs WB, Bagchi D, Bagchi M, Blum SH, Williams L, Braverman ER, Kerner M, Waite RL, Quirk B, White L, Reinking J (2008c) Dopamine D2 receptor Taq A1 allele predicts treatment compliance of LG839 in a subset analysis of pilot study in the Netherlands. Gene Ther Mol Biol 12:129–140
Blum K, Chen TJ, Downs BW, Bowirrat A, Waite RL, Braverman ER, Madigan M, Oscar-Berman M, DiNubile N, Stice E, Giordano J, Morse S, Gold M (2009) Neurogenetics of dopaminergic receptor supersensitivity in activation of brain reward circuitry and relapse: proposing “deprivation-amplification relapse therapy” (DART). Postgrad Med 121(6):176–196
Blum K, Chen TJ, Morse S, Giordano J, Chen AL, Thompson J, Allen C, Smolen A, Lubar J, Stice E, Downs BW, Waite RL, Madigan MA, Kerner M, Fornari F, Braverman ER (2010) Overcoming qEEG abnormalities and reward gene deficits during protracted abstinence in male psychostimulant and polydrug abusers utilizing putative dopamine D2 agonist therapy: part 2. Postgrad Med 122(6):214–226
Blum K, Liu Y, Shriner R, Gold MS (2011a) Reward circuitry dopaminergic activation regulates food and drug craving behavior. Curr Pharm Des 17(12):1158–1167
Blum K et al (2011b) Understanding the high mind: humans are still evolving genetically. IIOAB J 2:1–22
Blum K, Oscar-Berman M, Giordano J, Downs B, Simpatico T, Han D, Femino J (2012) Neurogenetic impairments of brain reward circuitry links to reward deficiency syndrome (RDS): potential nutrigenomic induced dopaminergic activation. J Genet Syndr Gene Ther 3(4):1000e115
Blum K, Gardner E, Oscar-Berman M, Gold M (2012a) “Liking” and “wanting” linked to Reward Deficiency Syndrome (RDS): hypothesizing differential responsivity in brain reward circuitry. Curr Pharm Des 18(1):113–118
Blum K, Werner T, Carnes S, Carnes P, Bowirrat A, Giordano J, Oscar-Berman M, Gold M (2012b) Sex, drugs, and rock ‘n’ roll: hypothesizing common mesolimbic activation as a function of reward gene polymorphisms. J Psychoactive Drugs 44(1):38–55
Blum K, Chen AL, Giordano J, Borsten J, Chen TJ, Hauser M, Simpatico T, Femino J, Braverman ER, Barh D (2012c) The addictive brain: all roads lead to dopamine. J Psychoactive Drugs 44(2):134–143
Blum K, Giordano J, Hauser M, Saunders S, Campenella C, Han D, Smolen A, Borsten J, Downs BW, Waite RL, Braverman ER, Liu Y, Femino J, Simpatico T (2012d) Genetic addiction risk scores (GARS) coupled with the comprehensive analysis of reported drugs (CARD) provide diagnostic and outcome data supporting the need for Dopamine D2 agonist therapy: proposing a holistic – therapeutic model for reward deficiency syndrome (RDS). In: Omics addiction therapy conference, Las Vegas, 20 Aug 2012 (Keynote abstract)
Blum K, Berman MO, Stuller E, Miller D, Giordano J et al (2012e) Neurogenetics and nutrigenomics of neuro-nutrient therapy for Reward Deficiency Syndrome (RDS): clinical ramifications as a function of molecular neurobiological mechanisms. J Addict Res Ther 3:139. doi:10.4172/2155-6105.1000139
Blum et al. (2012f) Special issue proceedings of the meeting on addiction research and therapy, Journal Addiction Research and Therapy, Embassy Suites, Las Vegas, 20–22 August 2012
Blum K, Oscar-Berman M, Femino J, Waite RL, Benya L et al. (2013) Withdrawal from buprenorphine/naloxone and maintenance with a natural dopaminergic agonist: a cautionary note. J Addict Res Ther 4:146. doi:10.4172/2155-6105.1000146
Bossert JM, Gray SM, Lu L, Shaham Y (2006) Activation of group II metabotropic glutamate receptors in the nucleus accumbens shell attenuates context-induced relapse to heroin seeking. Neuropsychopharmacology 10:2197–2209
Boundy VA, Pacheco MA, Guan W, Molinoff PB (1995) Agonists and antagonists differentially regulate the high affinity state of the D2L receptor in human embryonic kidney 293 cells. Mol Pharmacol 48(5):956–964
Bowirrat A, Oscar-Berman M (2005) Relationship between dopaminergic neurotransmission, alcoholism, and Reward Deficiency Syndrome. Am J Med Genet B Neuropsychiatr Genet 132B(1):29–37
Bradaia A, Trube G, Stalder H, Norcross RD, Ozmen L, Wettstein JG, Pinard A, Buchy D, Gassmann M, Hoener MC, Bettler B (2009) The selective antagonist EPPTB reveals TAAR1-mediated regulatory mechanisms in dopaminergic neurons of the mesolimbic system. Proc Natl Acad Sci USA 106(47):20081–20086
Braverman ER, Chen AL, Chen TJ, Schoolfield JD, Notaro A, Braverman D, Kerner M, Blum SH, Arcuri V, Varshavskiy M, Damle U, Downs BW, Waite RL, Oscar-Berman M, Giordano J, Blum K. (2010) Test of variables of attention (TOVA) as a predictor of early attention complaints, an antecedent to dementia. Neuropsychiatr Dis Treat 6:681–690. doi: 10.2147/NDT.S12243.
Brown RJ, Blum K, Trachtenberg MC (1990) Neurodynamics of relapse prevention: a neuronutrient approach to outpatient DUI offenders. J Psychoactive Drugs 22(2):173–187
Budygin EA, Park J, Bass CE, Grinevich VP, Bonin KD, Wightman RM (2012) Aversive stimulus differentially triggers subsecond dopamine release in reward regions. Neuroscience 201:331–337
Burger KS, Stice E (2012) Frequent ice cream consumption is associated with reduced striatal response to receipt of an ice cream-based milkshake. Am J Clin Nutr 95(4):810–817
Byerley W, Hoff M, Holik J, Caron MG, Giros B (1993) VNTR polymorphism for the human dopamine transporter gene (DAT1). Hum Mol Genet 2(3):335
Chen TJ, Blum K, Payte JT, Schoolfield J, Hopper D, Stanford M, Braverman ER (2004) Narcotic antagonists in drug dependence: pilot study showing enhancement of compliance with SYN-10, amino-acid precursors and enkephalinase inhibition therapy. Med Hypotheses 63(3):538–548
Chen TJ, Blum K, Waite RL, Meshkin B, Schoolfield J, Downs BW, Braverman EE, Arcuri V, Varshavskiy M, Blum SH, Mengucci J, Reuben C, Palomo T (2007a) Narcotic Attenuation Program attenuates substance use disorder, a clinical subtype of reward deficiency syndrome. Adv Ther 24(2):402–414
Chen TJH, Blum K, Kaats G, Braverman ER, Eisenberg A et al (2007b) Chromium Picolinate (Crp) A putative anti-obesity nutrient induces changes in body composition as function of the Taq1 Dopamine D2 receptor polymorphisms in a randomized double-blind placebo controlled study. Gene Ther Mol Biol 11:161–170
Chen AL, Chen TJ, Waite RL, Reinking J, Tung HL, Rhoades P, Downs BW, Braverman E, Braverman D, Kerner M, Blum SH, DiNubile N, Smith D, Oscar-Berman M, Prihoda TJ, Floyd JB, O’Brien D, Liu HH, Blum K (2009) Hypothesizing that brain reward circuitry genes are genetic antecedents of pain sensitivity and critical diagnostic and pharmacogenomic treatment targets for chronic pain conditions. Med Hypotheses 72(1):14–22
Chen TJ, Blum K, Chen AL, Bowirrat A, Downs WB, Madigan MA, Waite RL, Bailey JA, Kerner M, Yeldandi S, Majmundar N, Giordano J, Morse S, Miller D, Fornari F, Braverman ER (2011) Neurogenetics and clinical evidence for the putative activation of the brain reward circuitry by a neuroadaptagen: proposing an addiction candidate gene panel map. J Psychoactive Drugs 43(2):108–127
Chen D, Liu Y, He W, Wang H, Wang Z (2012) Neurotransmitter-precursor-supplement intervention for detoxified heroin addicts. J Huazhong Univ Sci Technolog Med Sci 32(3):422–427. doi:10.1007/s11596-012-0073-z
Contini V, Marques FZ, Garcia CE, Hutz MH, Bau CH (2006) MAOA-uVNTR polymorphism in a Brazilian sample: further support for the association with impulsive behaviors and alcohol dependence. Am J Med Genet B Neuropsychiatr Genet 141B(3):305–308
Cook EH Jr, Stein MA, Krasowski MD, Cox NJ, Olkon DM, Kieffer JE, Leventhal BL (1995) Association of attention-deficit disorder and the dopamine transporter gene. Am J Hum Genet 56(4):993–998
Cordeira J, Rios M (2011) Weighing in the role of BDNF in the central control of eating behavior. Mol Neurobiol 44(3):441–448
Dahlgren A, Wargelius HL, Berglund KJ, Fahlke C, Blennow K, Zetterberg H, Oreland L, Berggren U, Balldin J (2011) Do alcohol-dependent individuals with DRD2 A1 allele have an increased risk of relapse? A pilot study. Alcohol Alcohol 46(5):509–513
David V, Matifas A, Gavello-Baudy S, Decorte L, Kieffer BL, Cazala P (2008) Brain regional FOS expression elicited by the activation of mu- but not delta-opioid receptors of the ventral tegmental area: evidence for an implication of the ventral thalamus in opiate reward. Neuropsychopharmacology 33(7):1746–1759
DeFrance JF, Hymel C, Trachtenberg MC, Ginsberg LD, Schweitzer FC, Estes S, Chen TJ, Braverman ER, Cull JG, Blum K (1997) Enhancement of attention processing by Kantroll in healthy humans: a pilot study. Clin Electroencephalogr 28(2):68–75
Demetrovics Z, Varga G, Szekely A, Vereczkei A, Csorba J, Balazs H, Hoffman K, Sasvari-Szekely M, Barta C (2010) Association between Novelty Seeking of opiate-dependent patients and the catechol-O-methyltransferase Val(158)Met polymorphism. Compr Psychiatry 51(5):510–515
Duaux E, Gorwood P, Griffon N, Bourdel MC, Sautel F, Sokoloff P, Schwartz JC, Ades J, Lôo H, Poirier MF (1998) Homozygosity at the dopamine D3 receptor gene is associated with opiate dependence. Mol Psychiatry 3(4):333–336
Dunn JP, Kessler RM, Feurer ID, Volkow ND, Patterson BW, Ansari MS, Li R, Marks-Shulman P, Abumrad NN (2012) Relationship of dopamine type 2 receptor binding potential with fasting neuroendocrine hormones and insulin sensitivity in human obesity. Diabetes Care 35(5):1105–1111
Faraone SV, Doyle AE, Mick E, Biederman J (2001) Meta-analysis of the association between the 7-repeat allele of the dopamine D(4) receptor gene and attention deficit hyperactivity disorder. Am J Psychiatry 158(7):1052–1057
Feusner J, Ritchie T, Lawford B, Young RM, Kann B, Noble EP (2001) GABA(A) receptor beta 3 subunit gene and psychiatric morbidity in a post-traumatic stress disorder population. Psychiatry Res 104(2):109–117
Filip M, Zaniewska M, Frankowska M, Wydra K, Fuxe K (2012) The importance of the adenosine A(2A) receptor-dopamine D(2) receptor interaction in drug addiction. Curr Med Chem 19(3):317–355
Galeeva AR, Gareeva AE, Iur’ev EB, Khusnutdinova EK (2002) VNTR polymorphisms of the serotonin transporter and dopamine transporter genes in male opiate addicts. Mol Biol (Mosk) 36(4):593–598
Gokturk C, Schultze S, Nilsson KW, von Knorring L, Oreland L, Hallman J (2008) Serotonin transporter (5-HTTLPR) and monoamine oxidase (MAOA) promoter polymorphisms in women with severe alcoholism. Arch Womens Ment Health 11(5–6):347–355
Grzywacz A, Kucharska-Mazur J, Samochowiec J (2008) Association studies of dopamine D4 receptor gene exon 3 in patients with alcohol dependence. Psychiatr Pol 42(3):453–461
Hall FS, Sora I, Uhl GR (2001) Ethanol consumption and reward are decreased in mu-opiate receptor knockout mice. Psychopharmacology (Berl) 154(1):43–49
Hikida T, Kimura K, Wada N, Funabiki K, Nakanishi S (2010) Distinct roles of synaptic transmission in direct and indirect striatal pathways to reward and aversive behavior. Neuron 66(6):896–907
Hill SY, Hoffman EK, Zezza N, Thalamuthu A, Weeks DE, Matthews AG, Mukhopadhyay I (2008 Jun 5) Dopaminergic mutations: within-family association and linkage in multiplex alcohol dependence families. Am J Med Genet B Neuropsychiatr Genet 147B(4):517–526
Ide S, Minami M, Satoh M, Uhl GR, Sora I, Ikeda K (2004) Buprenorphine antinociception is abolished, but naloxone-sensitive reward is retained, in mu-opioid receptor knockout mice. Neuropsychopharmacology 29(9):1656–1663
Ikemoto S (2010) Brain reward circuitry beyond the mesolimbic dopamine system: a neurobiological theory. Neurosci Biobehav Rev 35(2):129–150. doi:10.1016/j.neubiorev.2010.02.001
Johnson PM, Kenny PJ (2012) Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nat Neurosci 13(5):635–641
Kita JM, Kile BM, Parker LE, Wightman RM (2009) In vivo measurement of somatodendritic release of dopamine in the ventral tegmental area. Synapse 63(11):951–960. doi:10.1002/syn.20676
Kosek E, Jensen KB, Lonsdorf TB, Schalling M, Ingvar M (2009) Genetic variation in the serotonin transporter gene (5-HTTLPR, rs25531) influences the analgesic response to the short acting opioid Remifentanil in humans. Mol Pain 5:37
Kotler M, Cohen H, Segman R, Gritsenko I, Nemanov L, Lerer B, Kramer I, Zer-Zion M, Kletz I, Ebstein RP (1997) Excess dopamine D4 receptor (D4DR) exon III seven repeat allele in opioid-dependent subjects. Mol Psychiatry 2(3):251–254
Kraschewski A, Reese J, Anghelescu I, Winterer G, Schmidt LG, Gallinat J, Finckh U, Rommelspacher H, Wernicke C (2009) Association of the dopamine D2 receptor gene with alcohol dependence: haplotypes and subgroups of alcoholics as key factors for understanding receptor function. Pharmacogenet Genomics 19(7):513–527
LaForge KS, Shick V, Spangler R, Proudnikov D, Yuferov V, Lysov Y, Mirzabekov A, Kreek MJ (2000) Detection of single nucleotide polymorphisms of the human mu opioid receptor gene by hybridization or single nucleotide extension on custom oligonucleotide gelpad microchips: potential in studies of addiction. Am J Med Genet 96(5):604–615
Lai JH, Zhu YS, Huo ZH, Sun RF, Yu B, Wang YP, Chai ZQ, Li SB (2010) Association study of polymorphisms in the promoter region ofDRD4 with schizophrenia, depression, and heroin addiction. Brain Res 1359:227–232
Lee SS, Lahey BB, Waldman I, Van Hulle CA, Rathouz P, Pelham WE, Loney J, Cook EH (2007) Association of dopamine transporter genotype with disruptive behavior disorders in an eight-year longitudinal study of children and adolescents. Am J Med Genet B Neuropsychiatr Genet 144B(3):310–317
Lee SY, Chen SL, Chen SH, Chu CH, Chang YH, Lin SH, Huang SY, Tzeng NS, Kuo PH, Lee IH, Yeh TL, Yang YK, Lu RB (2012) Interaction of the DRD3 and BDNF gene variants in subtyped bipolar disorder. Prog Neuropsychopharmacol Biol Psychiatry 39(2):382–387
Li CY, Mao X, Wei L (2008) Genes and (common) pathways underlying drug addiction. PLoS Comput Biol 4(1):e2, Epub 2007 Nov 20
Li T, Hou Y, Cao W, Yan CX, Chen T, Li SB (2012) Role of dopamine D3 receptors in basal nociception regulation and in morphine-induced tolerance and withdrawal. Brain Res 1433:80–84
Limosin F, Romo L, Batel P, Adès J, Boni C, Gorwood P (2005) Association between dopamine receptor D3 gene BalI polymorphism and cognitive impulsiveness in alcohol-dependent men. Eur Psychiatry 20(3):304–306
Lintas A, Chi N, Lauzon NM, Bishop SF, Gholizadeh S, Sun N, Tan H, Laviolette SR (2011) Identification of a dopamine receptor-mediated opiate reward memory switch in the basolateral amygdala-nucleus accumbens circuit. J Neurosci 31(31):11172–11183
Lobo MK, Covington HE 3rd, Chaudhury D, Friedman AK, Sun H, Damez-Werno D, Dietz DM, Zaman S, Koo JW, Kennedy PJ, Mouzon E, Mogri M, Neve RL, Deisseroth K, Han MH, Martinez D, Saccone PA, Liu F, Slifstein M, Orlowska D, Grassetti A, Cook S, Broft A, Van Heertum R, Comer SD (2012) Deficits in dopamine D(2) receptors and presynaptic dopamine in heroin dependence: commonalities and differences with other types of addiction. Boil Psychiatry 71(3):192–198
Martinez D, Saccone PA, Liu F, Slifstein M, Orlowska D, Grassetti A, Cook S, Broft A, Van Heertum R, Comer SD (2012) Deficits in dopamine D(2) receptors and presynaptic dopamine in heroin dependence: commonalities and differences with other types of addiction. Biol Psychiatry 71(3):192–198. doi:10.1016/j.biopsych.2011.08.024. Epub 19 Oct 2011
Merenäkk L, Mäestu J, Nordquist N, Parik J, Oreland L, Loit HM, Harro J (2011) Effects of the serotonin transporter (5-HTTLPR) and α2A-adrenoceptor (C-1291G) genotypes on substance use in children and adolescents: a longitudinal study. Psychopharmacology (Berl) 215(1):13–22
Mhatre M, Ticku MK (1994) Chronic ethanol treatment upregulates the GABA receptor beta subunitexpression. Brain Res Mol Brain Res 23(3):246–252
Miller DK, Bowirrat A, Manka M, Miller M, Stokes S, Manka D, Allen C, Gant C, Downs BW, Smolen A, Stevens E, Yeldandi S, Blum K (2010) Acute intravenous synaptamine complex variant KB220™ “normalizes” neurological dysregulation in patients during protracted abstinence from alcohol and opiates as observed using quantitative electroencephalographic and genetic analysis for reward polymorphisms: part 1, pilot study with 2 case reports. Postgrad Med 122(6):188–213
Miller M, Chen AL, Stokes SD, Silverman S, Bowirrat A, Manka M, Manka D, Miller DK, Perrine K, Chen TJ, Bailey JA, Downs W, Waite RL, Madigan MA, Braverman ER, Damle U, Kerner M, Giordano J, Morse S, Oscar-Berman M, Barh D, Blum K (2012) Early intervention of intravenous KB220IV- neuroadaptagen amino-acid therapy (NAAT) improves behavioral outcomes in a residential addiction treatment program: a pilot study. J Psychoactive Drugs 44(5):398–409
Mulert C, Juckel G, Giegling I, Pogarell O, Leicht G, Karch S, Mavrogiorgou P, Möller HJ, Hegerl U, Rujescu D (2006) A Ser9Gly polymorphism in the dopamine D3 receptor gene (DRD3) and event-related P300 potentials. Neuropsychopharmacology 31(6):1335–1344
Myers RD, Robinson DE (1999) Mmu and D2 receptor antisense oligonucleotides injected in nucleus accumbens suppress high alcohol intake in genetic drinking HEP rats. Alcohol 18(2–3):225–233
Namkoong K, Cheon KA, Kim JW, Jun JY, Lee JY (2008) Association study of dopamine D2, D4 receptor gene, GABAA receptor beta subunit gene, serotonin transporter gene polymorphism with children of alcoholics in Korea: a preliminary study. Alcohol 42(2):77–81
Nedic G, Nikolac M, Sviglin KN, Muck-Seler D, Borovecki F, Pivac N (2011) Association study of a functional catechol-O-methyltransferase (COMT) Val108/158Met polymorphism and suicide attempts in patients with alcohol dependence. Int J Neuropsychopharmacol 4(3):377–388
Nestler EJ (2010) Cell type-specific loss of BDNF signaling mimics optogenetic control of cocaine reward. Science 330(6002):385–390
Neville MJ, Johnstone EC, Walton RT (2004) Identification and characterization of ANKK1: a novel kinase gene closely linked to DRD2 on chromosome band 11q23.1. Hum Mutat 23(6):540–545
Niehaus JL, Cruz-Bermúdez ND, Kauer JA (2009) Plasticity of addiction: a mesolimbic dopamine short-circuit? J Addict 18(4):259–271
Nikulina V, Widom CS, Brzustowicz LM (2012) Child abuse and neglect, MAOA, and mental health outcomes: a prospective examination. Biol Psychiatry 71(4):350–357
Nilsson KW, Comasco E, Åslund C, Nordquist N, Leppert J, Oreland L (2011) MAOA genotype, family relations and sexual abuse in relation to adolescent alcohol consumption. Addict Biol 16(2):347–355
Noble EP, Blum K, Ritchie T, Montgomery A, Sheridan PJ (1991) Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism. Arch Gen Psychiatry 48(7):648–654
Noble EP, Zhang X, Ritchie T, Lawford BR, Grosser SC, Young RM, Sparkes RS (1998) D2 dopamine receptor and GABA(A) receptor beta3 subunit genes and alcoholism. Psychiatry Res 81(2):133–147
Palomo T, Archer T, Kostrzewa RM, Beninger RJ (2007) Comorbidity of substance abuse with other psychiatric disorders. Neurotox Res 12(1):17–27
Paloyelis Y, Asherson P, Mehta MA, Faraone SV, Kuntsi J (2010) DAT1 and COMT effects on delay discounting and trait impulsivity in male adolescents with attention deficit/hyperactivity disorder and healthy controls. Neuropsychopharmacology 35(12):2414–2426
Perez MF, Ford KA, Goussakov I, Stutzmann GE, Hu XT (2011) Repeated cocaine exposure decreases dopamine D-like receptor modulation of Ca(2+) homeostasis in rat nucleus accumbens neurons. Synapse 65(2):168–180. doi:10.1002/syn.20831
Piechota M, Korostynski M, Solecki W, Gieryk A, Slezak M, Bilecki W, Ziolkowska B, Kostrzewa E, Cymerman I, Swiech L, Jaworski J, Przewlocki R (2010) The dissection of transcriptional modules regulated by various drugs of abuse in the mouse striatum. Genome Biol 11(5):R48. doi:10.1186/gb-2010-11-5-r48
Pierce R, Kumaresan V (2006) The mesolimbic dopamine system: the final common pathway for the reinforcing effect of drugs of abuse? Neurosci Biobehav Rev 30(2):215–238
Ray R, Ruparel K, Newberg A, Wileyto EP, Loughead JW, Divgi C, Blendy JA, Logan J, Zubieta JK, Lerman C (2011) Human Mu Opioid Receptor (OPRM1 A118G) polymorphism is associated with brain mu-opioid receptor binding potential in smokers. Proc Natl Acad Sci USA 108(22):9268–9273
Reese J, Kraschewski A, Anghelescu I, Winterer G, Schmidt LG, Gallinat J, Rüschendorf F, Rommelspacher H, Wernicke C (2010) Haplotypes of dopamine and serotonin transporter genes are associated with antisocial personality disorder in alcoholics. Psychiatr Genet 20(4):140–152
Ross J (2001) Amino-acid precursor and enkephalinase inhibition therapy: evidence for effectiveness in treatment of “Reward Deficiency Syndrome (RDS)” with particular emphasis on eating disorders. Mol Psychiatry 6(1 Suppl 1):S1–S8
Rothman RB (1994) A review of the effects of dopaminergic agents in humans: implications for medication development. NIDA Res Monogr 145:67–87
Salomone JD, Correa M (2012) The mysterious motivational functions of mesolimbic dopamine. Neuron 76(3):470–485
Schellekens AF, Franke B, Ellenbroek B, Cools A, de Jong CA, Buitelaar JK, Verkes RJ (2012) Reduced dopamine receptor sensitivity as an intermediate phenotype in alcohol dependence and the role of the COMT Val158Met and DRD2 Taq1A genotypes. Arch Gen Psychiatry 69(4):339–348
Self DW, Nestler EJ (1998) Relapse to drug-seeking: neural and molecular mechanisms. Drug Alcohol Depend 51(1–2):49–60
Smith DE (2012) The process addictions and the new ASAM definition of addiction. J Psychoactive Drugs 44(1):1–4
Spangler R, Wittkowski KM, Goddard NL, Avena NM, Hoebel BG, Leibowitz SF (2004) Opiate-like effects of sugar on gene expression in reward areas of the rat brain. Brain Res Mol Brain Res 124(2):134–142
Stice E, Yokum S, Blum K, Bohon C (2010) Weight gain is associated with reduced striatal response to palatable food. J Neurosci 30(39):13105–13109
Szeto CY, Tang NL, Lee DT, Stadlin A (2001) Association between mu opioid receptor gene polymorphisms and Chinese heroin addicts. Neuroreport 12(6):1103–1106
Teh LK, Izuddin AF, FH MH, Zakaria ZA, SAlleh MZ (2012) Tridimensional personalities and polymorphism of dopamine D2 receptor among heroin addicts. Biol Res Nurs 14(2):188–196
Thanos PK, Volkow ND, Freimuth P, Umegaki H, Ikari H, Roth G, Ingram DK, Hitzemann R (2001) Overexpression of dopamine D2 receptors self-administration. J Neurochem 78(5):1094–1103
Thanos PK, Taintor NB, Rivera SN, Umegaki H, Ikari H, Roth G, Ingram DK, Hitzemann R, Fowler JS, Gatley SJ, Wang GJ, Volkow ND (2004) DRD2 gene transfer into the nucleus accumbens core of the alcohol preferring and nonpreferring rats attenuates alcohol drinking. Alcohol Clin Exp Res 28(5):720–728
Thanos PK, Rivera SN, Weaver K, Grandy DK, Rubinstein M, Umegaki H, Wang GJ, Hitzemann R, Volkow ND (2005) Dopamine D2R DNA transfer in dopamine D2 receptor-deficient mice: effects on ethanol drinking. Life Sci 77(2):130–139
Thanos PK, Michaelides M, Umegaki H, Volkow ND (2008) D2R DNA transfer into the nucleus accumbens attenuates cocaine self-administration in rats. Synapse 62(7):481–486
Tikkanen R, Auvinen-Lintunen L, Ducci F, Sjöberg RL, Goldman D, Tiihonen J, Ojansuu I, Virkkunen M (2011) Psychopathy, PCL-R, and MAOA genotype as predictors of violent reconvictions. Psychiatry Res 185(3):382–386
Tomasi D, Volkow ND (2012) Striatocortical pathway dysfunction in addiction and obesity: differences and similarities. Crit Rev Biochem Mol Biol 48(1):1–19
Treister R, Pud D, Ebstein RP, Laiba E, Gershon E, Haddad M, Eisenberg E (2009) Associations between polymorphisms in dopamine neurotransmitter pathway genes and pain response in healthy humans. Pain 147(1–3):187–193
van der Zwaluw CS, Engels RC, Vermulst AA, Rose RJ, Verkes RJ, Buitelaar J, Franke B, Scholte RH (2010) A serotonin transporter polymorphism (5-HTTLPR) predicts the development of adolescent alcohol use. Drug Alcohol Depend 112(1–2):134–139
Van Tol HH (1998) Structural and functional characteristics of the dopamine D4 receptor. Adv Pharmacol 42:486–489
Vengeliene V, Leonardi-Essmann F, Perreau-Lenz S, Gebicke-Haerter P, Drescher K, Gross G, Spanagel R (2006) The dopamine D3 receptor plays an essential role in alcohol-seeking and relapse. FASEB J 20(13):2223–2233
Wahlstrom D, White T, Luciana M (2010) Neurobehavioral evidence for changes in dopamine system activity during adolescence. Neurosci Biobehav Neurosci Biobehav Rev 34(5):631–648
Wang GJ, Smith L, Volkow ND, Telang F, Logan J, Tomasi D, Wong CT, Hoffman W, Jayne M, Alia-Klein N, Thanos P, Fowler JS (2011) Decreased dopamine activity predicts relapse in methamphetamine abusers. Mol Psychiatry 17(9):918–925. doi:10.1038/mp.2011.86, Epub 2011 Jul 12
Yacubian J, Sommer T, Schroeder K, Gläscher J, Kalisch R, Leuenberger B, Braus DF, Büchel C (2007) Gene-gene interaction associated with neural reward sensitivity. Proc Natl Acad Sci USA 104(19):8125–8130
Young RM, Lawford BR, Feeney GF, Ritchie T, Noble EP (2004) Alcohol-related expectancies are associated with the D2 dopamine receptor and GABAA receptor beta3 subunitgenes. Psychiatry Res 127(3):171–183
Zhang L, Dong Y, Doyon WM, Dani JA (2012) Withdrawal from chronic nicotine exposure alters dopamine signaling dynamics in the nucleus accumbens. Biol Psychiatry 71(3):184–191
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Blum, K. et al. (2013). Neurogenetics and Nutrigenomics of Reward Deficiency Syndrome (RDS): Stratification of Addiction Risk and Mesolimbic Nutrigenomic Manipulation of Hypodopaminergic Function. In: Barh, D., Dhawan, D., Ganguly, N. (eds) Omics for Personalized Medicine. Springer, New Delhi. https://doi.org/10.1007/978-81-322-1184-6_18
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