Dopaminerge Genpolymorphismen und sportliche Höchstleistungen

Zusammenfassung

Dopaminerge Funktionen im Zusammenhang mit Lernen, kognitiver Kontrolle und Risikofreudigkeit beeinflussen nicht nur Alltagsverhalten, sondern auch sportliche (Höchst-)Leistungen. Im Zusammenhang mit Trainingsoptimierung und Leistungssteigerung erlangen in diesem Bereich genetisch bedingte Einflüsse auf die Funktionsweise des Dopaminsystems Bedeutung. Bisher sind zwei entsprechende Polymorphismen mit möglichen Bezügen zu sportlicher Leistung näher charakterisiert, die des Catechol-O-Methyltransferase-(COMT-) Enzyms sowie des Dopamintransporters (DAT). Dabei kann davon ausgegangen werden, dass die mit dem Met-Allel des COMT-Enzyms einhergehende erhöhte Konzentrations- und Aufmerksamkeitsleistung bzw. unter Umständen verringerte Stresstoleranz in Bezug auf sportliche Höchstleistungen relevant ist. Ebenso sollte sich die genetische Ausstattung bezüglich DAT auf Sportarten auswirken, bei denen Risikofreudigkeit eine Erfolgsvoraussetzung darstellt oder die hohe Anforderungen an das motorische Lernvermögen stellen. So könnte ein größerer sportlicher Er-folg für Risikosportarten mit der Trägerschaft des 10R-Allels verbunden sein.

Summary

Dopaminergic functions influence not only day-to-day behavior but also athletic accomplishments in the context of learning, cognitive control, and risk-taking. Along with efforts to improve training and enhance performance, genetically pre-determined factors influencing the functions of the dopamine system are a focus of interest. Until now, particularly two polymorphisms with possible repercussions on athletic achievement have been characterized: the catechol-o-methyltransferase (COMT) enzyme and the dopamine transporter (DAT). Accordingly, we can assume that better performance concerning concentration and attention, as well as reduced stress under certain circumstances that have been linked to the Met allele of the COMT enzyme, are relevant to athletic success. The genetic conditions should also have an effect on types of sports for which increased risk-taking or great motor learning capacity is a prerequisite for success. Carriers of the 10R allele could thereby be predisposed to greater success in risky sports.

Schlüsselwörter

Catechol-O-Methyltransferase-Enzym - Dopa-mintransporter - genetische Einflüsse - sportliche Höchstleistung

Keywords

Catechol-o-methyltransferase enzyme - dopamine transporter - genetic modulation - athletic peak performance

• Literatur

• 1 Cools R, Gibbs SE, Miyakawa A, Jagust W, D’Es-posito M. Working memory capacity predicts dopamine synthesis capacity in the human striatum. J Neurosc 2008; 28 (05) 1208-1212.
• 2 Beck F, Beckmann J. Die Rolle hippokampaler und striataler Plastizitätsvorgänge für motorisches Lernen. Deutsche Zeitschrift für Sportmedizin 2010; 61 (7–8) 157-162.
• 3 Beck F, Beckmann J. Die Bedeutung striataler Plastizitätsvorgänge und unerwarteten Bewegungserfolgs für sportmotorisches Lernen. Sportwissenschaft 2010; 40 (01) 19-25.
• 4 Jordet G. Why do English players fail in soccer penalty shootouts? A study of team status, self-regulation, and choking under pressure. J Sports Sci 2009; 27 (02) 97-106.
• 5 Jordet G, Hartman E, Visscher C, Lemmink KAPM. Kicks from the penalty mark in soccer: The roles of stress, skill, and fatigue for kick outcomes. J Sports Sci 2007; 25 (02) 121-129.
• 6 Drechsler R. Exekutive Funktionen. Übersicht und Taxonomie. Zeitschrift für Neuropsychologie 2007; 18: 233-248.
• 7 Kubesch S. Körperliche Aktivität und exekutive Funktionen. Reihe Junge Sportwissenschaft Schorndorf: Hoffmann Verlag; 2008
• 8 McDonald AW, Cohen JD, Stenger VA, Carter CS. Dissociating the role of the dorsolateral prefrontal and anterior cingulated cortex in cognitive control. Science 2000; 288: 1835-1838.
• 9 Medalla M, Barbas H. Synapses with inhibitory neurons differentiate anterior cingulate from dorsolateral prefrontal pathways associated with cognitive control. Neuron 2009; 61 (04) 609-620.
• 10 DiGirolamo GJ, Kramer AF, Barad V, Cepeda NJ, Weissman DH, Milham MP, Wszalek TM, Cohen NJ, Banich MT, Webb A. General and task-specific frontal lobe recruitment in older adults during executive processes: a fMRI investigation of task-switching. Neuroreport 2001; 12: 2065-2071.
• 11 Casey BJ, Thomas KM, Welsh TF, Badgaiyan RD, Eccard CH, Jennings JR, Crone EA. Dissociation of response conflict, attentional selection, and expectancy with functional magnetic resonance imaging. Proc Natl Acad Sci USA 2000; 97: 8728-8733.
• 12 Kubesch S, Walk L. Körperliches und kognitives Training exekutiver Funktionen in Kindergarten und Schule. Sportwissenschaft 2009; 39: 309-317.
• 13 McMorris T, Tomporowski P, Audiffren M. Exercise and cognitive function. West-Sussex: John Wiley & Sons; 2009
• 14 Posner IM, Rothbart MK. Educating the human brain. Washington: American Psychological Association; 2007
• 15 Karoum F, Chrapusta SJ, Egan MF. 3-Methoxytryramine is the major metabolite of released dopamine in the rat frontal cortex: reassessment of the effects of antipsychotics on the dynamics of dopamine release and metabolism in the frontal cortex, nucleus accumbens, and striatum by a simple two pool model. J Neurochem 1994; 63: 972-979.
• 16 Cozato LS, Pratt J, Hommel B. Dopaminergic control of attentional flexibility: inhibition of return is associated with the dopamine transporter gene (DAT1). Front Hum Neurosci 2010; 04: 1-6.
• 17 Diamond A, Briand L, Fossella J, Gehlbach L. Genetic and neurochemical modulation of prefrontal cognitive functions in children. Am J Psychiatry 2004; 161: 125-132.
• 18 Mier D, Kirsch P, Meyer-Lindenberg A. Neural substrates of pleiotropic action of genetic variation in COMT: a meta-analysis. Mol Psychiatry 2010; 15: 918-927.
• 19 Lotta T, Vidgren J, Tilgmann C, Ulmanen I, Melen K, Julkunen I, Taskinen J. Kinetics of human soluble and membrane-bound catechol-O-methyltransferase: a revised mechanism and description of the thermolabile variant of the enzyme. Biochemistry 1995; 34: 4202-4210.
• 20 Lachman HM, Papolos DF, Saito T, Yu YM, Szumlanski CL, Weinshilboum RM. Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Phar-macogenetics 1996; 06: 243-250.
• 21 Blair C, Diamond A. Biological processes in prevention and intervention: The promotion of self regulation as a means of preventing school failure. Dev Psychopathol 2008; 20: 899-911.
• 22 Palmatier MA, Kang AM, Kidd KK. Global variation in the frequencies of functionally different catechol-O-methyltransferase alleles. Biol Psychiatry 1999; 15: 557-567.
• 23 Diamond A, Briand L, Fossella J, Gehlbach L. Genetic and neurochemical modulation of prefrontal cognitive functions in children. Am J Psychiatry 2004; 161: 125-132.
• 24 Egan MF, Goldberg TE, Kolachana BS, Callicott JH, Mazzanti CM, Straub RE, Goldman D, Weinberger DR. Effect of COMT Val108/158Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci USA 2001; 98: 6917-6922.
• 25 TingKuang Y, Chun-Yen C, Chung-Yi H, Ting-Chi Y, Ming-Yeh L. Association of catechol-O-methyltransferase (COMT) polymorphism and academic achievement in a Chinese cohort. Brain Cogn 2009; 71: 300-305.
• 26 Kubesch S, Walk L, Hille K. Association of cathechol O-methyltransferaser (COMT) polymorphism and executive function in adolescents. Posterpresentation at the EARLI SIG Neuroscience and Education Meeting, Juni Zürich. 2010
• 27 Kempton MJ, Haldane M, Jogia J, Christodoulou T, Powell J, Collier D, Williams SCR, Frangou S. The effects of gender and COMT Val158Met polymorphism on fearful facial affect recognition: a fMRI study. Int J Neuropsychopharmacology 2010; 12: 371-381.
• 28 Diamond A. Consequences of variations in genes that affect dopamine in prefrontal cortex. Cerebral Cortex 2007; 17: 161-170.
• 29 Cohn CK, Axelrod J. The effect of estradiol on catechol-Omethyltransferase activity in rat liver. J Life Sci 1971; 10: 1351-1354.
• 30 Boudikova B, Szumlanski C, Maidak B, Weinshilboum R. Human liver catechol-O-methyltransferase pharmacogenetics. Clin Pharmacol Ther 1990; 48: 381-389.
• 31 Zahrt J, Taylor JR, Mathew RG, Arnsten AFT. Supra-normal stimulation of D1 dopamine receptors in the rodent prefrontal cortex impairs spatial working memory performance. J Neurosci 1997; 17: 8528-8535.
• 32 Mattay VS, Goldberg TE, Fera F, Hariri AR, Tessitore A, Egan MF, Kolachana B, Callicott JH, Weinberger DR. Catechol Omethyltransferase val158-met genotype and individual variation in the brain response to amphetamine. Proc Natl Acad Sci USA 2003; 100: 6186-6191.
• 33 Shors TJ, Miesegaes G. Testosterone in utero and at birth dictates how stressful experience will affect learning in adulthood. Proc Natl Acad Sci USA 2002; 99: 13955-13960.
• 34 Shors TJ, Leuner B. Estrogen-mediated effects on depression and memory formation in females. J Affect Disord 2003; 74: 85-96.
• 35 Shansky RM, Glavis-Bloom C, Lerman D, McRae P, Benson C, Miller K, Cosand L, Horvath TL, Arnsten AF. Estrogen mediates sex differences in stress-induced-prefrontal cortex dysfunction. Mol Psychiatry 2004; 09: 531-538.
• 36 Fan J, Gu X, Guise KG, Liu X, Fossella J, Wang H, Posner MI. Testing the behavioral interaction and integration of attentional networks. Brain Cogn 2009; 70: 209-220.
• 37 Kubesch S, Beck F. I go wild! Neurobiologie des Extremsports. Persönlichkeitsstörungen 2009; 13: 249-257.
• 38 Beauducel A, Strobel A, Brocke B. Psychometrische Eigenschaften und Normen einer deutschsprachigen Fassung der Sensation Seeking-Skalen, Form V. Diagnostica 2003; 49: 61-72.
• 39 Zuckerman M. Behavioural expressions and biosocial bases of sensation seeking. New York: Cambridge University Press; 1994
• 40 Moeller FG, Barratt ES, Dougherty DM, Schmitz JM, Swann AC. Psychiatric aspects of impulsivity. Am J Psychiatry 2001; 158 (11) 1783-93.
• 41 Zuckerman M, Kuhlman DM. Personality and risk-taking: common biosocial factors. J Pers 2000; 68 (06) 999-1029.
• 42 Sesack SR, Hawrylak VA, Guido MA, Levey AI. Cellular and subcellular localization of the dopamine transporter in rat cortex. Adv Pharmacol 1998; 42: 171-4.
• 43 Bannon MJ, Michelhaugh SK, Wang J, Sacchetti P. The human dopamine transporter gene: gene organization, transcriptional regulation, and potential involvement in neuropsychiatric disorders. Eur Neuropsychopharmacol 2001; 11 (06) 449-55.
• 44 Jacobsen LK, Staley JK, Zoghbi SS, Seibyl JP, Kosten TR, Innis RB, Gelernter J. Prediction of dopamine transporter binding availability by genotype: a preliminary report. Am J Psychiatry 2000; 157 (10) 1700-3.
• 45 van Dyck CH, Malison RT, Jacobsen LK, Seibyl JP, Staley JK, Laruelle M, Baldwin RM, Innis RB, Gelernter J. Increased dopamine transporter availability associated with the 9-repeat allele of the SLC6A3 gene. J Nucl Med 2005; 46 (05) 745-51.
• 46 Heinz A, Goldman D, Jones DW, Palmour R, Hommer D, Gorey JG, Lee KS, Linnoila M, Weinberger DR. Genotype influences in vivo dopamine transporter availability in human striatum. Neuropsychopharmacology 2000; 22 (02) 133-9.
• 47 VanNess SH, Owens MJ, Kilts CD. The variable number of tandem repeats element in DAT1 regulates in vitro dopamine transporter density. BMC Genet 2005; 06: 55.
• 48 Guo G, Tong Y, Xie CW, Lange LA. Dopamine transporter, gender, and number of sexual partners among young adults. Eur J Hum Genet 2007; 15 (03) 279-87.
• 49 Jaber M, Jones S, Giros B, Caron MG. The dopamine transporter: a crucial component regulating dopamine transmission. Mov Disord 1997; 12 (05) 629-33.
• 50 Maggos CE, Spangler R, Zhou Y, Schlussman SD, Ho A, Kreek MJ. Quantitation of dopamine transporter mRNA in the rat brain: mapping, effects of “binge” cocaine administration and withdrawal. Synapse 1997; 26 (01) 55-61.
• 51 Berridge KC. The debate over dopamine’s role in reward: the case for incentive salience. Psychopharmacology (Berl) 2007; 191 (03) 391-431.
• 52 Schultz W. Multiple reward signals in the brain. Nat Rev Neurosci 2000; 01 (03) 199-207.
• 53 Schultz W. Behavioral dopamine signals. Trends Neurosci 2007; 30 (05) 203-10.
• 54 Salahpour A, Ramsey AJ, Medvedev IO, Kile B, Sotnikova TD, Holmstrand E, Ghisi V, Nicholls PJ, Wong L, Murphy K, Sesack SR, Wightman RM, Gainetdinov RR, Caron MG. Increased amphetamine-induced hyperactivity and reward in mice over-expressing the dopamine transporter. Proc Natl Acad Sci USA 2008; 105 (11) 4405-10.
• 55 Ralph RJ, Paulus MP, Fumagalli F, Caron MG, Geyer MA. Prepulse inhibition deficits and perseverative motor patterns in dopamine transporter knockout mice: differential effects of D1 and D2 receptor antagonists. J Neurosci 2001; 21 (01) 305-13.
• 56 Zhang X, Bearer EL, Boulat B, Hall FS, Uhl GR, Jacobs RE. Altered neurocircuitry in the dopamine transporter knockout mouse brain. PLoS One 2010; 05 (07) e11506.
• 57 Guo G, Cai T, Guo R, Wang H, Harris KM. The dopamine transporter gene, a spectrum of most common risky behaviors, and the legal status of the behaviors. PLoS One 2010; 05 (02) e9352.
• 58 Sabol SZ, Nelson ML, Fisher C, Gunzerath L, Brody CL, Hu S, Sirota LA, Marcus SE, Greenberg BD, Lucas FRt, Benjamin J, Murphy DL, Hamer DH. A genetic association for cigarette smoking behavior. Health Psychol 1999; 18 (01) 7-13.
• 59 Timberlake DS, Haberstick BC, Lessem JM, Smolen A, Ehringer M, Hewitt JK, Hopfer C. An association between the DAT1 polymorphism and smoking behavior in young adults from the National Longitudinal Study of Adolescent Health. Health Psychol 2006; 25 (02) 190-7.
• 60 Erblich J, Lerman C, Self DW, Diaz GA, Bovbjerg DH. Effects of dopamine D2 receptor (DRD2) and transporter (SLC6A3) polymorphisms on smoking cue-induced cigarette craving among African-American smokers. Mol Psychiatry 2005; 10 (04) 407-14.
• 61 Franklin TR, Lohoff FW, Wang Z, Sciortino N, Harper D, Li Y, Jens W, Cruz J, Kampman K, Ehrman R, Berrettini W, Detre JA, O’Brien CP, Child-ress AR. DAT genotype modulates brain and behavioral responses elicited by cigarette cues. Neur-opsychopharmacology 2009; 34 (03) 717-28.
• 62 Forbes EE, Brown SM, Kimak M, Ferrell RE, Manuck SB, Hariri AR. Genetic variation in components of dopamine neurotransmission impacts ventral striatal reactivity associated with impulsivity. Mol Psychiatry 2009; 14 (01) 60-70.
• 63 Dreher JC, Kohn P, Kolachana B, Weinberger DR, Berman KF. Variation in dopamine genes influences responsivity of the human reward system. Proc Natl Acad Sci USA 2009; 106 (02) 617-22.
• 64 Beck A, Schlagenhauf F, Wustenberg T, Hein J, Kienast T, Kahnt T, Schmack K, Hagele C, Knutson B, Heinz A, Wrase J. Ventral striatal activation during reward anticipation correlates with impulsivity in alcoholics. Biol Psychiatry 2009; 66 (08) 734-42.
• 65 Reuter J, Raedler T, Rose M, Hand I, Glascher J, Buchel C. Pathological gambling is linked to reduced activation of the mesolimbic reward system. Nat Neurosci 2005; 08 (02) 147-8.
• 66 Yacubian J, Sommer T, Schroeder K, Glascher J, Kalisch R, Leuenberger B, Braus DF, Buchel C. Gene-gene interaction associated with neural reward sensitivity. Proc Natl Acad Sci USA 2007; 104 (19) 8125-30.
• 67 Robbins TW, Everitt BJ. Neurobehavioural mechanisms of reward an motivation. Curr Opin Neurobiol 1996; 290: 213-242.
• 68 Grefen CR. Functional neuroanatomy of dopamine in the striatum. In: Iversen LL, Iversen SD, Dunnett SB, Björklund A. Dopamine Handbook. New York: Oxford University Press; 2010
• 69 Williams SM, Goldman-Rakic PS. Widespread origin of the primate mesofrontal dopamine system. Cerebral Cortex 1998; 08: 321-345.
• 70 Ciliax BJ, Heilman C, Demchyshyn LL, Pristupa ZB, Ince E, Hersch SM, Niznik HB, Levey A. The dopamine transporter: immunochemical characterization and localization in brain. J Neurosci 1995; 15: 1714-1723.
• 71 Giros B, Jaber M, Jones SR, Wightman RM, Caron MG. Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature 1996; 379: 606-612.
• 72 Bilder RM, Volavka J, Lachman HM, Grace AA. (2004) The catechol-o-methyltransferase polymorphism: relations to the tonic-phasic hypothesis and neuropsychiatric phenotypes. Neuropsychopharmacology 2004; 29: 1943-1961.
• 73 Flöel A, Breitenstein C, Hummel F, Celnik P, Gingert C, Sawaki L, Knecht S, Cohen LG. Dopaminergic influences on formation of a motor memory. Ann Neurol 2005; 58: 121-130.
• 74 Willuhn I, Steiner H. Motor-skill learning in a novel running-wheel task is dependent on D1 dopamine receptors in the striatum. Neuroscience 2008; 153: 249-258.
• 75 Schultz W. Multiple reward signals in the brain. Nat Rev Neurosci 2010; 01: 199-207.
• 76 Pessiglione M, Seymour B, Flandin G, Dolan RJ, Frith CD. Dopamine-dependent prediction errors underpin reward-seeking behaviour in humans. Nature 2006; 442: 1042-1045.
• 77 Abler B, Hahlbrock R, Unrath A, Grön G, Kassubek J. At-risk pathological gambling: imaging neural reward processing under chronic dopamine agonists. Brain 2009; 132: 2396-2402.
• 78 Palminteri S, Lebreton M, Worbe Y, Grabli D, Hart-mann A, Pessiglione M. Pharmacological modulation of subliminal learning in Parkinson’s and Tourette’s syndromes. Proc Nat Acad Sci USA 2009; 106: 19179-19184.
• 79 Haruno M, Kuroda T, Doya K, Toyama K, Kimura M, Samejima K, Imamizu H, Kawato M. A neural correlate of reward-based behavioural learning in caudate nucleus: a functional magnetic resonance imaging study of a stochastic decision task. J Neurosci 2004; 24: 1660-1665.
• 80 Haruno M, Kawato M. Heterarchical reinforcement-learning model for integration of multiple corticostriatal loops: fMRI examination in stimulus-action-reward association learning. Neural Network 2006; 19: 1242-1254.
• 81 Schonberg T, Daw ND, Joel D, O’Doherty JP. Reinforcement learning signals in the human striatum distinguish learners from nonlearners during reward-based decision making. J Neurosci 2007; 27: 12880-12867.
• 82 Valentin VV, O’Doherty JP. Overlapping prediction errors in dorsal striatum during instrumental learning with juice and money reward in the human brain. J Neurophysiol 2009; 102: 3384-3391.
• 83 Volkow ND, Chang L, Wang GJ, Fowler JS, Leonido-Yee M, Franceschi D, Sedler MJ, Gatley MJ, Hitzemann R, Ding Y-S, Logan J, Wong C, Miller EN. Association of dopamine transporter reduction with psychomotor impairment in methamphetamine abusers. Am J Psychiatry 2001; 158: 377-382.
• 84 Carbon M, Ma Y, Barnes A, Dhawan V, Chaly T, Ghilardi MF, Eidelberg D. Caudate nucleus: influence of dopaminergic input on sequence learning and brain activation in parkinsonism. NeuroImage 2004; 21: 1497-1507.