Top

Published in:

01-04-2013 | Neurology and Preclinical Neurological Studies - Review Article

Genetics of impulse control disorders in Parkinson’s disease

Authors: Florence Cormier, Julia Muellner, Jean-Christophe Corvol

Published in: Journal of Neural Transmission | Issue 4/2013

Abstract

Impulse control disorders (ICD) have been recognised in Parkinson’s disease (PD) as adverse effects of dopamine replacement therapy, particularly with dopamine agonists. Although virtually all PD patients are treated with dopaminergic drugs, only a minority will develop hyperdopaminergic states, suggesting predisposing and/or protecting factors. The age at onset, the sex and the dose or type of dopaminergic drugs have been identified as clinical predictive factors. Recent genetic studies have investigated associations between ICD and polymorphisms of genes involved in the dopamine metabolism pathway (COMT, DAT), dopamine receptors (DRD1, DRD2, DRD3, DRD4), serotonin receptors and its transporter (HTR2A, 5HTT), and glutamate receptors (GRIN2B). Although validation in larger and independent cohorts is needed, the results from these studies give us some insights into the pathophysiology of hyperdopaminergic states and may be useful, at term, in personalising antiparkinsonian treatment in clinical practice.

Althaus M, Groen Y, Wijers AA, Mulder LJ, Minderaa RB, Kema IP, Dijck JD, Hartman CA, Hoekstra PJ (2009) Differential effects of 5-HTTLPR and DRD2/ANKK1 polymorphisms on electrocortical measures of error and feedback processing in children. Clin Neurophysiol 120(1):93–107. doi:10.1016/j.clinph.2008.10.012 PubMedCrossRef

Antonini A, Siri C, Santangelo G, Cilia R, Poletti M, Canesi M, Caporali A, Mancini F, Pezzoli G, Ceravolo R, Bonuccelli U, Barone P (2011) Impulsivity and compulsivity in drug-naive patients with Parkinson’s disease. Mov Disord 26(3):464–468. doi:10.1002/mds.23501 PubMedCrossRef

Ardouin C, Chereau I, Llorca PM, Lhommee E, Durif F, Pollak P, Krack P (2009) Assessment of hyper- and hypodopaminergic behaviors in Parkinson’s disease. Rev Neurol (Paris) 165(11):845–856. doi:10.1016/j.neurol.2009.06.003 CrossRef

Black DW, Moyer T (1998) Clinical features and psychiatric comorbidity of subjects with pathological gambling behavior. Psychiatr Serv 49(11):1434–1439PubMed

Brewer JA, Potenza MN (2008) The neurobiology and genetics of impulse control disorders: relationships to drug addictions. Biochem Pharmacol 75(1):63–75. doi:10.1016/j.bcp.2007.06.043 PubMedCrossRef

Comings DE, Gade R, Wu S, Chiu C, Dietz G, Muhleman D, Saucier G, Ferry L, Rosenthal RJ, Lesieur HR, Rugle LJ, MacMurray P (1997) Studies of the potential role of the dopamine D1 receptor gene in addictive behaviors. Mol Psychiatry 2(1):44–56PubMedCrossRef

Comings DE, Gade-Andavolu R, Gonzalez N, Wu S, Muhleman D, Chen C, Koh P, Farwell K, Blake H, Dietz G, MacMurray JP, Lesieur HR, Rugle LJ, Rosenthal RJ (2001) The additive effect of neurotransmitter genes in pathological gambling. Clin Genet 60(2):107–116. pii:cge600204 PubMedCrossRef

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):993–998PubMed

Cornish KM, Manly T, Savage R, Swanson J, Morisano D, Butler N, Grant C, Cross G, Bentley L, Hollis CP (2005) Association of the dopamine transporter (DAT1) 10/10-repeat genotype with ADHD symptoms and response inhibition in a general population sample. Mol Psychiatry 10(7):686–698. doi:10.1038/sj.mp.4001641 PubMedCrossRef

da Silva Lobo DS, Vallada HP, Knight J, Martins SS, Tavares H, Gentil V, Kennedy JL (2007) Dopamine genes and pathological gambling in discordant sib-pairs. J Gambl Stud 23(4):421–433. doi:10.1007/s10899-007-9060-x PubMedCrossRef

Ebstein RP, Nemanov L, Klotz I, Gritsenko I, Belmaker RH (1997) Additional evidence for an association between the dopamine D4 receptor (D4DR) exon III repeat polymorphism and the human personality trait of novelty seeking. Mol Psychiatry 2(6):472–477PubMedCrossRef

Eisen SA, Lin N, Lyons MJ, Scherrer JF, Griffith K, True WR, Goldberg J, Tsuang MT (1998) Familial influences on gambling behavior: an analysis of 3359 twin pairs. Addiction 93(9):1375–1384PubMedCrossRef

Eisenegger C, Knoch D, Ebstein RP, Gianotti LR, Sandor PS, Fehr E (2010) Dopamine receptor D4 polymorphism predicts the effect of l-DOPA on gambling behavior. Biol Psychiatry 67(8):702–706. doi:10.1016/j.biopsych.2009.09.021 PubMedCrossRef

Floresco SB, Tse MT, Ghods-Sharifi S (2008) Dopaminergic and glutamatergic regulation of effort- and delay-based decision making. Neuropsychopharmacology 33(8):1966–1979. doi:10.1038/sj.npp.1301565 PubMedCrossRef

Forbes EE, Brown SM, Kimak M, Ferrell RE, Manuck SB, Hariri AR (2009) Genetic variation in components of dopamine neurotransmission impacts ventral striatal reactivity associated with impulsivity. Mol Psychiatry 14(1):60–70. doi:10.1038/sj.mp.4002086 PubMedCrossRef

Frank MJ, Seeberger LC, O’Reilly RC (2004) By carrot or by stick: cognitive reinforcement learning in Parkinsonism. Science 306(5703):1940–1943. doi:10.1126/science.1102941 PubMedCrossRef

Gelernter J, Kranzler HR, Satel SL, Rao PA (1994) Genetic association between dopamine transporter protein alleles and cocaine-induced paranoia. Neuropsychopharmacology 11(3):195–200. doi:10.1038/sj.npp.1380106 PubMedCrossRef

Gorwood P, Le Strat Y, Ramoz N, Dubertret C, Moalic JM, Simonneau M (2012) Genetics of dopamine receptors and drug addiction. Hum Genet 131(6):803–822. doi:10.1007/s00439-012-1145-7 PubMedCrossRef

Grice DE, Leckman JF, Pauls DL, Kurlan R, Kidd KK, Pakstis AJ, Chang FM, Buxbaum JD, Cohen DJ, Gelernter J (1996) Linkage disequilibrium between an allele at the dopamine D4 receptor locus and Tourette syndrome, by the transmission-disequilibrium test. Am J Hum Genet 59(3):644–652PubMed

Guo G, Tong Y, Xie CW, Lange LA (2007) Dopamine transporter, gender, and number of sexual partners among young adults. Eur J Hum Genet 15(3):279–287. doi:10.1038/sj.ejhg.5201763 PubMedCrossRef

Heils A, Teufel A, Petri S, Stober G, Riederer P, Bengel D, Lesch KP (1996) Allelic variation of human serotonin transporter gene expression. J Neurochem 66(6):2621–2624PubMedCrossRef

Heinz A, Goldman D, Jones DW, Palmour R, Hommer D, Gorey JG, Lee KS, Linnoila M, Weinberger DR (2000) Genotype influences in vivo dopamine transporter availability in human striatum. Neuropsychopharmacology 22(2):133–139. doi:10.1016/S0893-133X(99)00099-8 PubMedCrossRef

Heitland I, Oosting RS, Baas JM, Massar SA, Kenemans JL, Bocker KB (2012) Genetic polymorphisms of the dopamine and serotonin systems modulate the neurophysiological response to feedback and risk taking in healthy humans. Cogn Affect Behav Neurosci. doi:10.3758/s13415-012-0108-8 PubMed

Hersrud SL, Stoltenberg SF (2009) Epistatic interaction between COMT and DAT1 genes on eating behavior: a pilot study. Eat Behav 10(2):131–133. doi:10.1016/j.eatbeh.2009.01.003 PubMedCrossRef

Holden C (2001) ‘Behavioral’ addictions: do they exist? Science 294(5544):980–982. doi:10.1126/science.294.5544.980 PubMedCrossRef

Ibanez A, Blanco C, Perez de Castro I, Fernandez-Piqueras J, Saiz-Ruiz J (2003) Genetics of pathological gambling. J Gambl Stud 19(1):11–22PubMedCrossRef

Juhasz G, Downey D, Hinvest N, Thomas E, Chase D, Toth ZG, Lloyd-Williams K, Mekli K, Platt H, Payton A, Bagdy G, Elliott R, Deakin JF, Anderson IM (2010) Risk-taking behavior in a gambling task associated with variations in the tryptophan hydroxylase 2 gene: relevance to psychiatric disorders. Neuropsychopharmacology 35(5):1109–1119. doi:10.1038/npp.2009.216 PubMedCrossRef

Kalivas PW, Volkow ND (2005) The neural basis of addiction: a pathology of motivation and choice. Am J Psychiatry 162(8):1403–1413. doi:10.1176/appi.ajp.162.8.1403 PubMedCrossRef

Karkowski LM, Prescott CA, Kendler KS (2000) Multivariate assessment of factors influencing illicit substance use in twins from female–female pairs. Am J Med Genet 96(5):665–670. doi:10.1002/1096-8628(20001009)96:5<665AID-AJMG13>3.0.CO;2-O PubMedCrossRef

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):251–254PubMedCrossRef

Kreek MJ, Nielsen DA, LaForge KS (2004) Genes associated with addiction: alcoholism, opiate, and cocaine addiction. Neuromolecular Med 5(1):85–108. doi:10.1385/NMM:5:1:085 PubMedCrossRef

Kreek MJ, Nielsen DA, Butelman ER, LaForge KS (2005) Genetic influences on impulsivity, risk taking, stress responsivity and vulnerability to drug abuse and addiction. Nat Neurosci 8(11):1450–1457. doi:10.1385/NMM:5:1:085 PubMedCrossRef

Kuhnen CM, Chiao JY (2009) Genetic determinants of financial risk taking. PLoS ONE 4(2):e4362. doi:10.1371/journal.pone.0004362 PubMedCrossRef

LaHoste GJ, Swanson JM, Wigal SB, Glabe C, Wigal T, King N, Kennedy JL (1996) Dopamine D4 receptor gene polymorphism is associated with attention deficit hyperactivity disorder. Mol Psychiatry 1(2):121–124PubMed

Lee JY, Lee EK, Park SS, Lim JY, Kim HJ, Kim JS, Jeon BS (2009) Association of DRD3 and GRIN2B with impulse control and related behaviors in Parkinson’s disease. Mov Disord 24(12):1803–1810. doi:10.1002/mds.22678 PubMedCrossRef

Lee JY, Jeon BS, Kim HJ, Park SS (2012) Genetic variant of HTR2A associates with risk of impulse control and repetitive behaviors in Parkinson’s disease. Parkinsonism Relat Disord 18(1):76–78. doi:10.1016/j.parkreldis.2011.08.009 PubMedCrossRef

Lesch KP, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S, Benjamin J, Muller CR, Hamer DH, Murphy DL (1996) Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274(5292):1527–1531PubMedCrossRef

Lotta T, Vidgren J, Tilgmann C, Ulmanen I, Melen K, Julkunen I, Taskinen J (1995) Kinetics of human soluble and membrane-bound catechol O-methyltransferase: a revised mechanism and description of the thermolabile variant of the enzyme. Biochemistry 34(13):4202–4210PubMedCrossRef

Muramatsu T, Higuchi S (1995) Dopamine transporter gene polymorphism and alcoholism. Biochem Biophys Res Commun 211(1):28–32. doi:10.1006/bbrc.1995.1773 PubMedCrossRef

Ness V, Arning L, Niesert HE, Stuttgen MC, Epplen JT, Beste C (2011) Variations in the GRIN2B gene are associated with risky decision-making. Neuropharmacology 61(5–6):950–956. doi:10.1016/j.neuropharm.2011.06.023 PubMedCrossRef

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. doi:10.1002/humu.20039 PubMedCrossRef

Noble EP (2000) Addiction and its reward process through polymorphisms of the D2 dopamine receptor gene: a review. Eur Psychiatry 15(2):79–89. doi:10.1016/S0924-9338(00)00208-X PubMedCrossRef

Perez de Castro I, Ibanez A, Torres P, Saiz-Ruiz J, Fernandez-Piqueras J (1997) Genetic association study between pathological gambling and a functional DNA polymorphism at the D4 receptor gene. Pharmacogenetics 7(5):345–348PubMed

Perez-Lloret S, Rey MV, Fabre N, Ory F, Spampinato U, Montastruc JL, Rascol O (2012) Do Parkinson’s disease patients disclose their adverse events spontaneously? Eur J Clin Pharmacol 68(5):857–865. doi:10.1007/s00228-011-1198-x PubMedCrossRef

Primus RJ, Thurkauf A, Xu J, Yevich E, McInerney S, Shaw K, Tallman JF, Gallagher DW (1997) II. Localization and characterization of dopamine D4 binding sites in rat and human brain by use of the novel, D4 receptor-selective ligand [3H]NGD 94–1. J Pharmacol Exp Ther 282(2):1020–1027PubMed

Rao H, Mamikonyan E, Detre JA, Siderowf AD, Stern MB, Potenza MN, Weintraub D (2010) Decreased ventral striatal activity with impulse control disorders in Parkinson’s disease. Mov Disord 25(11):1660–1669. doi:10.1002/mds.23147 PubMedCrossRef

Retz W, Rosler M, Supprian T, Retz-Junginger P, Thome J (2003) Dopamine D3 receptor gene polymorphism and violent behavior: relation to impulsiveness and ADHD-related psychopathology. J Neural Transm 110(5):561–572. doi:10.1007/s00702-002-0805-5 PubMedCrossRef

Rogers RD (2011) The roles of dopamine and serotonin in decision making: evidence from pharmacological experiments in humans. Neuropsychopharmacology 36(1):114–132. doi:10.1038/npp.2010.165 PubMedCrossRef

Sabol SZ, Nelson ML, Fisher C, Gunzerath L, Brody CL, Hu S, Sirota LA, Marcus SE, Greenberg BD, Lucas FR 4th, Benjamin J, Murphy DL, Hamer DH (1999) A genetic association for cigarette smoking behavior. Health Psychol 18(1):7–13PubMedCrossRef

Sander T, Harms H, Podschus J, Finckh U, Nickel B, Rolfs A, Rommelspacher H, Schmidt LG (1997) Allelic association of a dopamine transporter gene polymorphism in alcohol dependence with withdrawal seizures or delirium. Biol Psychiatry 41(3):299–304. pii:S0006322396000443 PubMedCrossRef

Shinohara M, Mizushima H, Hirano M, Shioe K, Nakazawa M, Hiejima Y, Ono Y, Kanba S (2004) Eating disorders with binge-eating behaviour are associated with the s allele of the 3′-UTR VNTR polymorphism of the dopamine transporter gene. J Psychiatry Neurosci 29(2):134–137PubMed

Slutske WS, Eisen S, True WR, Lyons MJ, Goldberg J, Tsuang M (2000) Common genetic vulnerability for pathological gambling and alcohol dependence in men. Arch Gen Psychiatry 57(7):666–673. doi:yoa9396 PubMedCrossRef

Stoltenberg SF, Vandever JM (2010) Gender moderates the association between 5-HTTLPR and decision-making under ambiguity but not under risk. Neuropharmacology 58(2):423–428. doi:10.1016/j.neuropharm.2009.09.010 PubMedCrossRef

Vallelunga A, Flaibani R, Formento-Dojot P, Biundo R, Facchini S, Antonini A (2012) Role of genetic polymorphisms of the dopaminergic system in Parkinson’s disease patients with impulse control disorders. Parkinsonism Relat Disord 18(4):397–399. doi:10.1016/j.parkreldis.2011.10.019 PubMedCrossRef

Van Tol HH, Wu CM, Guan HC, Ohara K, Bunzow JR, Civelli O, Kennedy J, Seeman P, Niznik HB, Jovanovic V (1992) Multiple dopamine D4 receptor variants in the human population. Nature 358(6382):149–152. doi:10.1038/358149a0 PubMedCrossRef

Vandenbergh DJ, Persico AM, Hawkins AL, Griffin CA, Li X, Jabs EW, Uhl GR (1992) Human dopamine transporter gene (DAT1) maps to chromosome 5p15.3 and displays a VNTR. Genomics 14(4):1104–1106PubMedCrossRef

Vandenbergh DJ, Rodriguez LA, Miller IT, Uhl GR, Lachman HM (1997) High-activity catechol-O-methyltransferase allele is more prevalent in polysubstance abusers. Am J Med Genet 74(4):439–442. doi:10.1002/(SICI)1096-8628(19970725)74:4<439:AID-AJMG16>3.0.CO;2-J PubMedCrossRef

Volberg RA (1994) The prevalence and demographics of pathological gamblers: implications for public health. Am J Public Health 84(2):237–241PubMedCrossRef

Voon V, Sohr M, Lang AE, Potenza MN, Siderowf AD, Whetteckey J, Weintraub D, Wunderlich GR, Stacy M (2011) Impulse control disorders in Parkinson disease: a multicenter case–control study. Ann Neurol 69(6):986–996. doi:10.1002/ana.22356 PubMedCrossRef

Weintraub D, Koester J, Potenza MN, Siderowf AD, Stacy M, Voon V, Whetteckey J, Wunderlich GR, Lang AE (2010) Impulse control disorders in Parkinson disease: a cross-sectional study of 3090 patients. Arch Neurol 67(5):589–595. doi:10.1001/archneurol.2010.65 PubMedCrossRef

Wilson D, da Silva Lobo DS, Tavares H, Gentil V, Vallada H (2012) Family-based association analysis of serotonin genes in pathological gambling disorder: evidence of vulnerability risk in the 5HT-2A receptor gene. J Mol Neurosci. doi:10.1007/s12031-012-9846-x

Title: Genetics of impulse control disorders in Parkinson’s disease
Authors: Florence Cormier
Julia Muellner
Jean-Christophe Corvol
Publication date: 01-04-2013
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 4/2013
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-012-0934-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Genetics of impulse control disorders in Parkinson’s disease

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2013

A cross-sectional multicenter study of cognitive and behavioural features in multiple system atrophy patients of the parkinsonian and cerebellar type

Non-motor symptoms of Parkinson’s disease: the patient’s perspective

The impact of deep brain stimulation on the nonmotor symptoms of Parkinson’s disease

Instruments for holistic assessment of Parkinson’s disease

Imaging impulse control disorders in Parkinson’s disease and their relationship to addiction

The pharmacology of Tourette syndrome