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Current Pharmaceutical Biotechnology

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ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Case Report

Hypodopaminergia and “Precision Behavioral Management” (PBM): It is a Generational Family Affair

Author(s): Lyle Fried, Edward J. Modestino, David Siwicki, Lisa Lott, Panayotis K. Thanos, David Baron, Rajendra D. Badgaiyan, Jessica V. Ponce , James Giordano, William B. Downs, Marjorie C. Gondré-Lewis, Steinberg Bruce, Eric R. Braverman, Brent Boyett and Kenneth Blum*

Volume 21, Issue 6, 2020

Page: [528 - 541] Pages: 14

DOI: 10.2174/1389201021666191210112108

Price: $65

Abstract

Background/Aims: This case series presents the novel Genetic Addiction Risk Score (GARS®) coupled with a customized pro-dopamine regulator matched to polymorphic reward genes having a hypodopaminergic risk.

Methods: The proband is a female with a history of drug abuse and alcoholism. She experienced a car accident under the influence and voluntarily entered treatment. Following an assessment, she was genotyped using the GARS, and started a neuronutrient with a KB220 base indicated by the identified polymorphisms. She began taking it in April 2018 and continues.

Results: She had success in recovery from Substance Use Disorder (SUD) and improvement in socialization, family, economic status, well-being, and attenuation of Major Depression. She tested negative over the first two months in treatment and a recent screening. After approximately two months, her parents also decided to take the GARS and started taking the recommended variants. The proband’s father (a binge drinker) and mother (no SUD) both showed improvement in various behavioral issues. Finally, the proband’s biological children were also GARS tested, showing a high risk for SUD.

Conclusion: This three-generation case series represents an example of the impact of genetic information coupled with an appropriate DNA guided “Pro-Dopamine Regulator” in recovery and enhancement of life.

Keywords: Substance Use Disorder (SUD), brain reward circuitry, hypodopaminergia, pro-dopamine regulator (KB220Z), Genetic Addiction Risk Score (GARS®), Precision Behavioral Management (PBM®), Precision Addiction Management (PAM®).

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Graphical Abstract
[1]
Blum, K.; Modestino, E.J.; Lott, L.; Siwicki, D.; Baron, D.; Howeedy, A.; Badgaiyan, R.D. Introducing “Precision Addiction Management (PAM®)” as an adjunctive genetic guided therapy for abusable drugs in America. Open Access J Behav Sci Psychol, 2018, 1(2), 1-4.
[PMID: 30662982]
[2]
Blum, K.; Sheridan, P.J.; Wood, R.C.; Braverman, E.R.; Chen, T.J.; Cull, J.G.; Comings, D.E. The D2 dopamine receptor gene as a determinant of reward deficiency syndrome. J. R. Soc. Med., 1996, 89(7), 396-400.
[http://dx.doi.org/10.1177/014107689608900711] [PMID: 8774539]
[3]
Blum, K. Reward deficiency syndrome. The SAGE Encyclopedia of Abnormal and Clinical Psychology; Wenzel, A., Ed. Sage Publications:University of Pennsylvania School of Medicine, USA , 2017; pp. 4-200.
[4]
Chen, T.J.; Blum, K.; Mathews, D.; Fisher, L.; Schnautz, N.; Braverman, E.R.; Schoolfield, J.; Downs, B.W.; Comings, D.E. Are dopaminergic genes involved in a predisposition to pathological aggression? Hypothesizing the importance of “super normal controls” in psychiatricgenetic research of complex behavioral disorders. Med. Hypotheses, 2005, 65(4), 703-707.
[http://dx.doi.org/10.1016/j.mehy.2005.04.037] [PMID: 15964153]
[5]
Blum, K.; Gondré-Lewis, M.C.; Baron, D.; Thanos, P.K.; Braverman, E.R.; Neary, J.; Elman, I. Introducing precision addiction management of reward deficiency syndrome, the construct that underpins all addictive behaviors. Front. Psychiatry, 2018, 9(548)
[6]
Bolos, A.M.; Dean, M.; Lucas-Derse, S.; Ramsburg, M.; Brown, G.L.; Goldman, D. Population and pedigree studies reveal a lack of association between the dopamine D2 receptor gene and alcoholism. JAMA, 1990, 264(24), 3156-3160.
[http://dx.doi.org/10.1001/jama.1990.03450240058040] [PMID: 1979357]
[7]
Blum, K.; Noble, E.P.; Sheridan, P.J.; Montgomery, A.; Ritchie, T.; Jagadeeswaran, P.; Nogami, H.; Briggs, A.H.; Cohn, J.B. Allelic association of human dopamine D2 receptor gene in alcoholism. JAMA, 1990, 263(15), 2055-2060.
[http://dx.doi.org/10.1001/jama.1990.03440150063027] [PMID: 1969501]
[8]
Noble, E.P.; Blum, K.; Ritchie, T.; Montgomery, A.; Sheridan, P.J. Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism. Arch. Gen. Psychiatry, 1991, 48(7), 648-654.
[http://dx.doi.org/10.1001/archpsyc.1991.01810310066012] [PMID: 2069496]
[9]
Peciña, M.; Mickey, B.J.; Love, T.; Wang, H.; Langenecker, S.A.; Hodgkinson, C.; Shen, P.H.; Villafuerte, S.; Hsu, D.; Weisenbach, S.L.; Stohler, C.S.; Goldman, D.; Zubieta, J.K. DRD2 polymorphisms modulate reward and emotion processing, dopamine neurotransmission and openness to experience. Cortex, 2013, 49(3), 877-890.
[http://dx.doi.org/10.1016/j.cortex.2012.01.010] [PMID: 22424959]
[10]
Noble, E.P. Polymorphisms of the D2 dopamine receptor gene and alcoholism and other substance use disorders. Alcohol Alcohol. Suppl., 1994, 2, 35-43.
[PMID: 8974314]
[11]
Comings, D.E.; Blum, K. Reward deficiency syndrome: genetic aspects of behavioral disorders. Prog. Brain Res., 2000, 126, 325-341.
[http://dx.doi.org/10.1016/S0079-6123(00)26022-6] [PMID: 11105655]
[12]
Noble, E.P. D2 dopamine receptor gene in psychiatric and neurologic disorders and its phenotypes. Am. J. Med. Genet. Part B, , 2003, 116(b1), 103-125.
[http://dx.doi.org/10.1002/ajmg.b.10005]
[13]
Gyollai, A.; Griffiths, M.D.; Barta, C.; Vereczkei, A.; Urbán, R.; Kun, B.; Kökönyei, G.; Székely, A.; Sasvári-Székely, M.; Blum, K.; Demetrovics, Z. The genetics of problem and pathological gambling: a systematic review. Curr. Pharm. Des., 2014, 20(25), 3993-3999.
[http://dx.doi.org/10.2174/13816128113199990626] [PMID: 24001288]
[14]
Stice, E.; Yokum, S.; Burger, K.; Epstein, L.; Smolen, A. Multilocus genetic composite reflecting dopamine signaling capacity predicts reward circuitry responsivity. J. Neurosci., 2012, 32(29), 10093-10100.
[http://dx.doi.org/10.1523/JNEUROSCI.1506-12.2012] [PMID: 22815523]
[15]
Carpenter, C.L.; Wong, A.M.; Li, Z.; Noble, E.P.; Heber, D. Association of dopamine D2 receptor and leptin receptor genes with clinically severe obesity. Obesity (Silver Spring), 2013, 21(9), E467-E473.
[PMID: 23670889]
[16]
Lowenstein, E.G.; Velazquez-Ulloa, N.A. A Fly’s eye view of natural and drug reward. Front. Physiol., 2018, 9, 407.
[http://dx.doi.org/10.3389/fphys.2018.00407] [PMID: 29720947]
[17]
Geller, I.; Blum, K. The effects of 5-HTP on para-Chlorophenylalanine (p-CPA) attenuation of “conflict” behavior. Eur. J. Pharmacol., 1970, 9(3), 319-324.
[http://dx.doi.org/10.1016/0014-2999(70)90229-3] [PMID: 5440301]
[18]
Blum, K.; Gondré-Lewis, M.; Steinberg, B.; Elman, I.; Baron, D.; Modestino, E.J.; Badgaiyan, R.D.; Gold, M.S. Our evolved unique pleasure circuit makes humans different from apes: Reconsideration of data derived from animal studies. J. Syst. Integr. Neurosci., 2018, 4(1)
[http://dx.doi.org/10.15761/JSIN.1000191] [PMID: 30956812]
[19]
Blum, K.; Kozlowski, G.P. Ethanol and neuromodulators interaction: A cascade model of reward. Alcohol and Behavior; Ollat, H.; Parvez, S; Parvez, H., Ed.; VSP Press Utrecht: The Netherlands, 1990.
[20]
Modestino, E.J.; Blum, K.; Oscar-Berman, M.; Gold, M.S.; Duane, D.D.; Sultan, S.G.S.; Auerbach, S.H. Reward deficiency syndrome: Attentional/arousal subtypes, limitations of current diagnostic nosology, and future research. J. Reward Defic. Syndr., 2015, 1(1), 6-9.
[http://dx.doi.org/10.17756/jrds.2015-002] [PMID: 26306327]
[21]
Pitchers, K.K.; Coppens, C.M.; Beloate, L.N.; Fuller, J.; Van, S.; Frohmader, K.S.; Laviolette, S.R.; Lehman, M.N.; Coolen, L.M. Endogenous opioid-induced neuroplasticity of dopaminergic neurons in the ventral tegmental area influences natural and opiate reward. J. Neurosci., 2014, 34(26), 8825-8836.
[http://dx.doi.org/10.1523/JNEUROSCI.0133-14.2014] [PMID: 24966382]
[22]
Marcello, F.; Grazia, S.M.; Sergio, M.; Federigo, S. Pharmacological “enkephalinase” inhibition in man. Adv. Exp. Med. Biol., 1986, 198, 153-160.
[http://dx.doi.org/10.1007/978-1-4757-0154-8_19]
[23]
Pariyadath, V.; Gowin, J.L.; Stein, E.A. Resting state functional connectivity analysis for addiction medicine: From individual loci to complex networks. Prog. Brain Res., 2016, 224, 155-173.
[http://dx.doi.org/10.1016/bs.pbr.2015.07.015] [PMID: 26822358]
[24]
Febo, M.; Blum, K.; Badgaiyan, R.D.; Perez, P.D.; Colon-Perez, L.M.; Thanos, P.K.; Ferris, C.F.; Kulkarni, P.; Giordano, J.; Baron, D.; Gold, M.S. Enhanced functional connectivity and volume between cognitive and reward centers of naïve rodent brain produced by pro-dopaminergic agent KB220Z. PLoS One, 2017, 12(4)e0174774
[http://dx.doi.org/10.1371/journal.pone.0174774] [PMID: 28445527]
[25]
Febo, M.; Blum, K.; Badgaiyan, R.D.; Baron, D.; Thanos, P.K.; Colon-Perez, L.M.; Demortrovics, Z.; Gold, M.S. Dopamine homeostasis: brain functional connectivity in reward deficiency syndrome. Front. Biosci., 2017, 22, 669-691.
[http://dx.doi.org/10.2741/4509] [PMID: 27814639]
[26]
Blum, K.; Liu, Y.; Wang, W.; Wang, Y.; Zhang, Y.; Oscar-Berman, M.; Smolen, A.; Febo, M.; Han, D.; Simpatico, T.; Cronjé, F.J.; Demetrovics, Z.; Gold, M.S. rsfMRI effects of KB220Z™ on neural pathways in reward circuitry of abstinent genotyped heroin addicts. Postgrad. Med., 2015, 127(2), 232-241.
[http://dx.doi.org/10.1080/00325481.2015.994879] [PMID: 25526228]
[27]
Blum, K.; Chen, T.H.; Chen, A.L.C.; Rhoades, P.; Prihoda, T.J.; Downs, W.B.; Bagchi, D.; Bagchi, M.; Blum, S.H.; Williams, L.; Braverman, E.R.; Kerner, M.; Waite, R.L.; Quirk, B.; White, L J. R., 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., 2008, 12, 129-140.
[28]
Blum, K.; Chen, A.L.; Chen, T.J.; Rhoades, P.; Prihoda, T.J.; Downs, B.W.; Waite, R.L.; Williams, L.; Braverman, E.R.; Braverman, D.; Arcuri, V.; Kerner, M.; Blum, S.H.; Palomo, T. LG839: anti-obesity effects and polymorphic gene correlates of reward deficiency syndrome. Adv. Ther., 2008, 25(9), 894-913.
[http://dx.doi.org/10.1007/s12325-008-0093-z] [PMID: 18781289]
[29]
Blum, K.; Chen, T.; Williams, L.; Chen, A.; Downs, B.; Waite, R.; Huntington, T.; Sims, S.; Prihoda, T.; Rhoads, P.; Reinking, J.; Braverman, D.; Kerner, M.; Blum, S.; Quirk, B.; Braverman, E. Correspondence, a short term pilot open label study to evaluate efficacy and safety of LG839, a customized DNA directed nutraceutical in obesity: Exploring nutrigenomics. Gene Ther. Molecul. Biol. Gene Ther. Mol. Biol. Vol., 2008, 12, 371-382.
[30]
Blum, K.; Chen, T.J.; Meshkin, B.; Downs, B.W.; Gordon, C.A.; Blum, S.; Mengucci, J.F.; Braverman, E.R.; Arcuri, V.; Varshavskiy, M.; Deutsch, R.; Martinez-Pons, M. Reward deficiency syndrome in obesity: a preliminary cross-sectional trial with a Genotrim variant. Adv. Ther., 2006, 23(6), 1040-1051.
[http://dx.doi.org/10.1007/BF02850224] [PMID: 17276971]
[31]
Blum, K.; Febo, M.; Badgaiyan, R.D.; Demetrovics, Z.; Simpatico, T.; Fahlke, C. Oscar-Berman, M.; Li, M.; Dushaj, K.; Gold, M.S.Common neurogenetic diagnosis and meso-limbic manipulation of hypodopaminergic function in Reward Deficiency Syndrome (RDS): Changing the recovery landscape. Curr. Neuropharmacol., 2017, 15(1), 184-194.
[http://dx.doi.org/10.2174/1570159X13666160512150918]
[32]
Lester, B.M.; Tronick, E.; Nestler, E.; Abel, T.; Kosofsky, B.; Kuzawa, C.W.; Marsit, C.J.; Maze, I.; Meaney, M.J.; Monteggia, L.M.; Reul, J.M.; Skuse, D.H.; Sweatt, J.D.; Wood, M.A. Behavioral epigenetics. Ann. N. Y. Acad. Sci., 2011, 1226, 14-33.
[http://dx.doi.org/10.1111/j.1749-6632.2011.06037.x] [PMID: 21615751]
[33]
Johnson, A.M.; Vernon, P.A.; McCarthy, J.M.; Molson, M.; Harris, J.A.; Jang, K.L. Nature vs nurture: are leaders born or made? A behavior genetic investigation of leadership style. Twin Res., 1998, 1(4), 216-223.
[34]
Castermans, E.; Gaillez, S.; Bours, V. [Are we genetically predisposed to addictions?]. Rev. Med. Liege, 2013, 68(5-6), 226-232.
[PMID: 23888569]
[35]
Corbier, J.R.; Chen, A.L.; Blum, K.; Downs, B.W.; Kushner, S.; Samples, R.; Modestino, E.J. Epigenetic repair of Reward Deficiency Syndrome (RDS) incorporating pro-dopamine regulation (KB220ZBR) in a neurological clinic. Case Report: Open Access, 2018, 4(2)
[36]
Blum, K.; Febo, M.; Fried, L.; Li, M.; Dushaj, K.; Braverman, E.R.; McLaughlin, T.; Steinberg, B.; Badgaiyan, R.D. Hypothesizing that neuropharmacological and neuroimaging studies of Glutaminergic-Dopaminergic Optimization Complex (KB220Z) are associated with “Dopamine Homeostasis” in Reward Deficiency Syndrome (RDS). Subst. Use Misuse, 2017, 52(4), 535-547.
[http://dx.doi.org/10.1080/10826084.2016.1244551] [PMID: 28033474]
[37]
Stice, E.; Yokum, S.; Blum, K.; Bohon, C. Weight gain is associated with reduced striatal response to palatable food. J. Neurosci., 2010, 30(39), 13105-13109.
[http://dx.doi.org/10.1523/JNEUROSCI.2105-10.2010] [PMID: 20881128]
[38]
Rothman, R.B.; Blough, B.E.; Baumann, M.H. Dual dopamine/serotonin releasers: potential treatment agents for stimulant addiction. Exp. Clin. Psychopharmacol., 2008, 16(6), 458-474.
[http://dx.doi.org/10.1037/a0014103] [PMID: 19086767]
[39]
Willuhn, I.; Burgeno, L.M.; Groblewski, P.A.; Phillips, P.E. Excessive cocaine use results from decreased phasic dopamine signaling in the striatum. Nat. Neurosci., 2014, 17(5), 704-709.
[http://dx.doi.org/10.1038/nn.3694] [PMID: 24705184]
[40]
Waite, M.R.; Skidmore, J.M.; Billi, A.C.; Martin, J.F.; Martin, D.M. GABAergic and glutamatergic identities of developing midbrain Pitx2 neurons. Dev. Dyn., 2011, 240(2), 333-346.
[http://dx.doi.org/10.1002/dvdy.22532] [PMID: 21246650]
[41]
van Huijstee, A.N.; Mansvelder, H.D. Glutamatergic synaptic plasticity in the mesocorticolimbic system in addiction. Front. Cell. Neurosci., 2015, 8, 466.
[http://dx.doi.org/10.3389/fncel.2014.00466] [PMID: 25653591]
[42]
Delis, F.; Thanos, P.K.; Rombola, C.; Rosko, L.; Grandy, D.; Wang, G.J.; Volkow, N.D. Chronic mild stress increases alcohol intake in mice with low dopamine D2 receptor levels. Behav. Neurosci., 2013, 127(1), 95-105.
[http://dx.doi.org/10.1037/a0030750] [PMID: 23148856]
[43]
El-Ghundi, M.; George, S.R.; Drago, J.; Fletcher, P.J.; Fan, T.; Nguyen, T.; Liu, C.; Sibley, D.R.; Westphal, H.; O’Dowd, B.F. Disruption of dopamine D1 receptor gene expression attenuates alcohol-seeking behavior. Eur. J. Pharmacol., 1998, 353(2-3), 149-158.
[http://dx.doi.org/10.1016/S0014-2999(98)00414-2] [PMID: 9726645]
[44]
Palmer, A.A.; Low, M.J.; Grandy, D.K.; Phillips, T.J. Effects of a Drd2 deletion mutation on ethanol-induced locomotor stimulation and sensitization suggest a role for epistasis. Behav. Genet., 2003, 33(3), 311-324.
[http://dx.doi.org/10.1023/A:1023450625826] [PMID: 12837020]
[45]
Phillips, T.J.; Brown, K.J.; Burkhart-Kasch, S.; Wenger, C.D.; Kelly, M.A.; Rubinstein, M.; Grandy, D.K.; Low, M.J. Alcohol preference and sensitivity are markedly reduced in mice lacking dopamine D2 receptors. Nat. Neurosci., 1998, 1(7), 610-615.
[http://dx.doi.org/10.1038/2843] [PMID: 10196569]
[46]
Risinger, F.O.; Freeman, P.A.; Rubinstein, M.; Low, M.J.; Grandy, D.K. Lack of operant ethanol self-administration in dopamine D2 receptor knockout mice. Psychopharmacology (Berl.), 2000, 152(3), 343-350.
[http://dx.doi.org/10.1007/s002130000548] [PMID: 11105945]
[47]
Thanos, P.K.; Rivera, S.N.; Weaver, K.; Grandy, D.K.; Rubinstein, M.; Umegaki, H.; Wang, G.J.; Hitzemann, R.; Volkow, N.D. Dopamine D2R DNA transfer in dopamine D2 receptor-deficient mice: effects on ethanol drinking. Life Sci., 2005, 77(2), 130-139.
[http://dx.doi.org/10.1016/j.lfs.2004.10.061] [PMID: 15862598]
[48]
Leggio, G.M.; Camillieri, G.; Platania, C.B.; Castorina, A.; Marrazzo, G.; Torrisi, S.A.; Nona, C.N.; D’Agata, V.; Nobrega, J.; Stark, H.; Bucolo, C.; Le Foll, B.; Drago, F.; Salomone, S. Dopamine D3 receptor is necessary for ethanol consumption: an approach with buspirone. Neuropsychopharmacology, 2014, 39(8), 2017-2028.
[http://dx.doi.org/10.1038/npp.2014.51]
[49]
Pearson-Fuhrhop, K.M.; Dunn, E.C.; Mortero, S.; Devan, W.J.; Falcone, G.J.; Lee, P.; Holmes, A.J.; Hollinshead, M.O.; Roffman, J.L.; Smoller, J.W.; Rosand, J.; Cramer, S.C. Dopamine genetic risk score predicts depressive symptoms in healthy adults and adults with depression. PLoS One, 2014, 9(5)e93772
[http://dx.doi.org/10.1371/journal.pone.0093772] [PMID: 24834916]
[50]
Guo, Y.; Zhang, H.; Gao, J.; Wei, S.; Song, C.; Sun, P.; Qiao, M. Study of genes associated with the ‘anger-in’ and ‘anger-out’ emotions of humans using a rat model. Exp. Ther. Med., 2015, 9(4), 1448-1454.
[http://dx.doi.org/10.3892/etm.2015.2246] [PMID: 25780450]

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