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Open Access 01-07-2018 | Original Article

Influence of the DRD2/ANKK1 Taq1A polymorphism on caudate volume in older adults without dementia

Authors: Xin Li, Goran Papenberg, Grégoria Kalpouzos, Lars Bäckman, Jonas Persson

Published in: Brain Structure and Function | Issue 6/2018

Abstract

Dopaminergic neuromodulation is critically important for brain and cognitive integrity. The DRD2/ANKK1 Taq1A polymorphism is associated with striatal dopamine (DA) D2 receptor availability. Some previous studies have found that the A allele of the Taq1A polymorphism influences brain structure, but the results are inconsistent, likely due to population heterogeneity and small sample sizes. We investigated the genetic effect on caudate volume in a large sample of older adults without dementia. Results show that A-allele carriers have smaller caudate volume compared to non-carriers in relatively older adults (n = 167; Mage = 77.8 years), whereas the genotype did not influence caudate volume in a younger age group (n = 220; Mage = 62.8 years). Cognitive performance was not significantly affected by the DRD2 gene. Our findings extend previous observations by showing magnified genetic effects on brain volume in old age, and provide evidence for a link between a DA-related genetic polymorphism and grey matter volume in a brain region within the nigrostriatal dopaminergic pathway.

Ashburner J (2007) A fast diffeomorphic image registration algorithm. NeuroImage 38(1):95–113. https://doi.org/10.1016/j.neuroimage.2007.07.007 CrossRefPubMed

Ashburner J, Friston KJ (2005) Unified segmentation. Neuroimage 26(3):839–851. https://doi.org/10.1016/j.neuroimage.2005.02.018 CrossRefPubMed

Bäckman L, Ginovart N, Dixon RA, Wahlin TBR, Wahlin A, Halldin C, Farde L (2000) Age-related cognitive deficits mediated by changes in the striatal dopamine system. Am J Psychiatry 157(4):635–637CrossRefPubMed

Bäckman L, Small BJ, Wahlin Å (2001) Aging and memory: cognitive and biological perspectives. In: Birren JE, Schaie KW (eds) Handbook of the Psychology of Aging, 5th edn. Academic Press, San Diego, pp 349–377

Bäckman L, Nyberg L, Soveri A, Johansson J, Andersson M, Dahlin E, Neely AS, Virta J, Laine M, Rinne JO (2011) Effects of working-memory training on striatal dopamine release. Science 333(6043):718–718. https://doi.org/10.1126/science.1204978 CrossRefPubMed

Bartres-Faz D, Junque C, Serra-Grabulosa JM, Lopez-Alomar A, Moya A, Bargallo N, Mercader JM, Moral P, Clemente IC (2002) Dopamine DRD2 Taq I polymorphism associates with caudate nucleus volume and cognitive performance in memory impaired subjects. Neuroreport 13(9):1121–1125. https://doi.org/10.1097/00001756-200207020-00010 CrossRefPubMed

Berry AS, Shah VD, Furman DJ, White RL III, Baker SL, O’Neil JP, Janabi M, D’Esposito M, Jagust WJ (2017) Dopamine synthesis capacity is associated with D2/3 receptor binding but not dopamine release. Neuropsychopharmacology. https://doi.org/10.1038/npp.2017.180 PubMedPubMedCentralCrossRef

Berryhill ME, Wiener M, Stephens JA, Lohoff FW, Coslett HB (2013) COMT and ANKK1-Taq-Ia genetic polymorphisms influence visual working memory. Plos One 8(1):7. https://doi.org/10.1371/journal.pone.0055862 CrossRef

Camps M, Cortes R, Gueye B, Probst A, Palacios JM (1989) Dopamine-receptors in human-brain—autoradiographic distribution of D2 sites. Neuroscience 28(2):275–290. https://doi.org/10.1016/0306-4522(89)90179-6 CrossRefPubMed

Cerasa A, Gioia MC, Tarantino P, Labate A, Arabia G, Annesi G, Lanza P, Di Palma G, Blasi V, Quattrone A (2009) The DRD2 TaqIA polymorphism associated with changed midbrain volumes in healthy individuals. Genes Brain Behav 8(4):459–463. https://doi.org/10.1111/j.1601-183X.2009.00492.x CrossRefPubMed

Cervenka S, Bäckman L, Cselenyi Z, Halldin C, Farde L (2008) Associations between dopamine D2-receptor binding and cognitive performance indicate functional compartmentalization of the human striatum. Neuroimage 40(3):1287–1295. https://doi.org/10.1016/j.neuroimage.2007.12.063 CrossRefPubMed

Colzato LS, van den Wildenberg WPM, Hommel B (2013) The genetic impact (C957T-DRD2) on inhibitory control is magnified by aging. Neuropsychologia 51(7):1377–1381. https://doi.org/10.1016/j.neuropsychologia.2013.01.014 CrossRefPubMed

Cools R (2011) Dopaminergic control of the striatum for high-level cognition. Curr Opin Neurobiol 21(3):402–407. https://doi.org/10.1016/j.conb.2011.04.002 CrossRefPubMed

Cools R, D’Esposito M (2011) Inverted-U-shaped dopamine actions on human working memory and cognitive control. Biol Psychiat 69(12):E113-E125. https://doi.org/10.1016/j.biopsych.2011.03.028 CrossRefPubMedCentral

Dahl M, Allwood CM, Hagberg B (2009) The realism in older people’s confidence judgments of answers to general knowledge questions. Psychol Aging 24(1):234CrossRefPubMed

Dahlin E, Neely AS, Larsson A, Bäckman L, Nyberg L (2008) Transfer of learning after updating training mediated by the striatum. Science 320(5882):1510–1512. https://doi.org/10.1126/science.1155466 CrossRefPubMed

Darki F, Peyrard-Janvid M, Matsson H, Kere J, Klingberg T (2012) Three dyslexia susceptibility genes, DYX1C1, DCDC2, and KIAA0319, affect temporo-parietal white matter structure. Biol Psychiat 72(8):671–676. https://doi.org/10.1016/j.biopsych.2012.05.008 CrossRefPubMed

Dureman I (1960) SRB:1. Stockholm. Psykologiförlaget, Sweden

Erixon-Lindroth N, Farde L, Wahlin TBR, Sovago J, Halldin C, Bäckman L (2005) The role of the striatal dopamine transporter in cognitive aging. Psychiatry Res Neuroimaging 138(1):1–12. https://doi.org/10.1016/j.pscychresns.2004.09.005 CrossRef

Fearnley JM, Lees AJ (1991) Ageing and Parkinson’s disease: substantia nigra regional selectivity. Brain J Neurol 114 (Pt 5):2283CrossRef

Folstein MF, Folstein SE, McHugh PR (1975) Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12(3):189–198CrossRefPubMed

Gunning-Dixon FM, Head D, McQuain J, Acker JD, Raz N (1998) Differential aging of the human striatum: a prospective MR imaging study. Am J Neuroradiol 19(8):1501–1507PubMed

Hall H, Sedvall G, Magnusson O, Kopp J, Halldin C, Farde L (1994) Distribution of D1-and D2-dopamine receptors, and dopamine and its metabolites in the human brain

Hariri AR, Drabant EM, Weinberger DR (2006) Imaging genetics: perspectives from studies of genetically driven variation in serotonin function and corticolimbic affective processing. Biol Psychiat 59(10):888–897. https://doi.org/10.1016/j.biopsych.2005.11.005 CrossRefPubMed

Harris SE, Deary IJ (2011) The genetics of cognitive ability and cognitive ageing in healthy older people. Trends Cognit Sci 15(9):388–394. https://doi.org/10.1016/j.tics.2011.07.004 CrossRef

Hirvonen M, Laakso A, Nagren K, Rinne JO, Pohjalainen T, Hietala J (2004) C957T polymorphism of the dopamine D2 receptor (DRD2) gene affects striatal DRD2 availability in vivo. Mol Psychiatry 9(12):1060–1061. https://doi.org/10.1038/sj.mp.4001561 CrossRefPubMed

Hoyer WJ, Verhaeghen P (2006) Memory aging. In: Birren JE, Schaie KW (eds) Handbook of the Psychology of Aging, 6th edn. Elsevier, Amsterdam, Netherlands, pp 209–232

Ito H, Kodaka F, Takahashi H, Takano H, Arakawa R, Shimada H, Suhara T (2011) Relation between presynaptic and postsynaptic dopaminergic functions measured by positron emission tomography: implication of dopaminergic tone. J Neurosci 31(21):7886–7890. https://doi.org/10.1523/jneurosci.6024-10.2011 CrossRefPubMed

Jack CR, Twomey CK, Zinsmeister AR, Sharbrough FW, Petersen RC, Cascino GD (1989) Anterior temporal lobes and hippocampal formations: normative volumetric measurements from MR images in young adults. Radiology 172(2):549–554CrossRefPubMed

Jocham G, Klein TA, Neumann J, von Cramon DY, Reuter M, Ullsperger M (2009) Dopamine DRD2 polymorphism alters reversal learning and associated neural activity. J Neurosci 29(12):3695–3704. https://doi.org/10.1523/jneurosci.5195-08.2009 CrossRefPubMedPubMedCentral

Jönsson EG, Nothen MM, Grunhage F, Farde L, Nakashima Y, Propping P, Sedvall GC (1999) Polymorphisms in the dopamine D2 receptor gene and their relationships to striatal dopamine receptor density of healthy volunteers. Mol Psychiatry 4(3):290–296. https://doi.org/10.1038/sj.mp.4000532 CrossRefPubMed

Karrer TM, Josef AK, Mata R, Morris ED, Samanez-Larkin GR (2017) Reduced dopamine receptors and transporters but not synthesis capacity in normal aging adults: a meta-analysis. Neurobiol Aging 57:36–46CrossRefPubMedPubMedCentral

Kish SJ, Shannak K, Rajput A, Deck JHN, Hornykiewicz O (1992) Aging produces a specific pattern of striatal dopamine loss: implications for the etiology of idiopathic Parkinson’s disease. J Neurochem 58(2):642–648. https://doi.org/10.1111/j.1471-4159.1992.tb09766.x CrossRefPubMed

Kline RB (2005) Principles and practice of structural equation modeling. Guilford, New York

Laukka EJ, Lövdén M, Herlitz A, Karlsson S, Ferencz B, Pantzar A, Keller L, Graff C, Fratiglioni L, Bäckman L (2013) Genetic effects on old-age cognitive functioning: a population-based study. Psychol Aging 28(1):262–274. https://doi.org/10.1037/a0030829 CrossRefPubMed

Li SC, Sikstrom S (2002) Integrative neurocomputational perspectives on cognitive aging, neuromodulation, and representation. Neurosci Biobehav Rev 26(7):795–808. https://doi.org/10.1016/s0149-7634(02)00066-0 CrossRefPubMed

Lindenberger U, Nagel IE, Chicherio C, Li SC, Heekeren HR, Bäckman L (2008) Age-related decline in brain resources modulates genetic effects on cognitive functioning. Front Neurosci 2(2):234–244. https://doi.org/10.3389/neuro.01.039.2008 CrossRefPubMedPubMedCentral

Liu F, Pardo LM, Schuur M, Sanchez-Juan P, Isaacs A, Sleegers K, de Koning I, Zorkoltseva IV, Axenovich TI, Witteman JCM, Janssens A, van Swieten JC, Aulchenko YS, Oostra BA, van Duijn CM (2010a) The apolipoprotein E gene and its age-specific effects on cognitive function. Neurobiol Aging 31(10):1831–1833. https://doi.org/10.1016/j.neurobiolaging.2008.09.015 CrossRefPubMed

Liu YW, Paajanen T, Westman E, Wahlund LO, Simmons A, Tunnard C, Sobow T, Proitsi P, Powell J, Mecocci P, Tsolaki M, Vellas B, Muehlboeck S, Evans A, Spenger C, Lovestone S, Soininen H, AddNeuroMed C (2010b) Effect of APOE epsilon 4 Allele on cortical thicknesses and volumes: the AddNeuroMed Study. J Alzheimers Dis 21(3):947–966. https://doi.org/10.3233/jad-2010-100201 CrossRefPubMed

Lövdén M, Laukka EJ, Rieckmann A, Kalpouzos G, Li TQ, Jonsson T, Wahlund LO, Fratiglioni L, Bäckman L (2013) The dimensionality of between-person differences in white matter microstructure in old age. Hum Brain Mapp 34(6):1386–1398. https://doi.org/10.1002/hbm.21518 CrossRefPubMed

Makris N, Gasic GP, Seidman LJ, Goldstein JM, Gastfriend DR, Elman I, Albaugh MD, Hodge SM, Ziegler DA, Sheahan FS, Caviness VS, Tsuang MT, Kennedy DN, Hyman SE, Rosen BR, Breiter HC (2004) Decreased absolute amygdala volume in cocaine addicts. Neuron 44(4):729–740. https://doi.org/10.1016/j.neuron.2004.10.027 CrossRefPubMed

Manos PJ, Wu R (1994) The ten point clock test: a quick screen and grading method for cognitive impairment in medical and surgical patients. Int J Psychiatry Med 24(3):229–244CrossRefPubMed

Martin WRW, Palmer MR, Patlak CS, Calne DB (1989) Nigrostriatal function in humans studied with positron emission tomography. Ann Neurol 26(4):535–542. https://doi.org/10.1002/ana.410260407 CrossRefPubMed

Mattay VS, Goldberg TE, Sambataro F, Weinberger DR (2008) Neurobiology of cognitive aging: Insights from imaging genetics. Biol Psychol 79(1):9–22. https://doi.org/10.1016/j.biopsycho.2008.03.015 CrossRefPubMedPubMedCentral

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. https://doi.org/10.1002/humu.20039 CrossRefPubMed

Nieoullon A (2002) Dopamine and the regulation of cognition and attention. Prog Neurobiol 67(1):53–83. https://doi.org/10.1016/s0301-0082(02)00011-4 CrossRefPubMed

Nilsson L-G, Bäckman L, Erngrund K, Nyberg L, Adolfsson R, Bucht G, Karlsson S, Widing M, Winblad B (1997) The betula prospective cohort study: memory, health, and aging. Aging Neuropsychol Cogn 4(1):1–32. https://doi.org/10.1080/13825589708256633 CrossRef

Nyberg L, Karalija N, Salami A, Andersson M, Wahlin A, Kaboovand N, Kohncke Y, Axelsson J, Rieckmann A, Papenberg G, Garrett DD, Riklund K, Lövdén M, Lindenberger U, Bäckman L (2016) Dopamine D2 receptor availability is linked to hippocampal-caudate functional connectivity and episodic memory. Proc Natl Acad Sci USA 113(28):7918–7923. https://doi.org/10.1073/pnas.1606309113 CrossRefPubMedPubMedCentral

O’Reilly RC, Frank MJ (2006) Making working memory work: a computational model of learning in the prefrontal cortex and basal ganglia. Neural Comput 18(2):283–328. https://doi.org/10.1162/089976606775093909 CrossRefPubMed

Papenberg G, Bäckman L, Nagel IE, Nietfeld W, Schroeder J, Bertram L, Heekeren HR, Lindenberger U, Li S-C (2013) COMT polymorphism and memory dedifferentiation in old age. Psychol Aging 29(2):374–383. https://doi.org/10.1037/a0033225 CrossRefPubMed

Papenberg G, Li S-C, Nagel IE, Nietfeld W, Schjeide B-M, Schroeder J, Bertram L, Heekeren HR, Lindenberger U, Bäckman L (2014) Dopamine and glutamate receptor genes interactively influence episodic memory in old age. Neurobiol Aging. https://doi.org/10.1016/j.neurobiolaging.2013.11.014 PubMedCrossRef

Papenberg G, Lindenberger U, Bäckman L (2015a) Aging-related magnification of genetic effects on cognitive and brain integrity. Trends Cogn Sci 19(9):506–514. https://doi.org/10.1016/j.tics.2015.06.008 CrossRefPubMed

Papenberg G, Lövdén M, Laukka EJ, Kalpouzos G, Keller L, Graff C, Kohncke Y, Li T-Q, Fratiglioni L, Bäckman L (2015b) Magnified effects of the COMT gene on white-matter microstructure in very old age. Brain Struct Funct 220(5):2927–2938. https://doi.org/10.1007/s00429-014-0835-4 CrossRefPubMed

Papenberg G, Ferencz B, Mangialasche F, Mecocci P, Cecchetti R, Kalpouzos G, Fratiglioni L, Bäckman L (2016) Physical activity and inflammation: effects on gray-matter volume and cognitive decline in aging. Hum Brain Mapp 37(10):3462–3473. https://doi.org/10.1002/hbm.23252 CrossRefPubMed

Persson J, Rieckmann A, Kalpouzos G, Fischer H, Bäckman L (2015) Influences of a DRD2 polymorphism on updating of long-term memory representations and caudate BOLD activity: magnification in aging. Hum Brain Mapp 36(4):1325–1334. https://doi.org/10.1002/hbm.22704 CrossRefPubMed

Pohjalainen T, Rinne JO, Nagren K, Lehikoinen P, Anttila K, Syvalahti EKG, Hietala J (1998) The A1 allele of the human D-2 dopamine receptor gene predicts low D-2 receptor availability in healthy volunteers. Mol Psychiatry 3(3):256–260. https://doi.org/10.1038/sj.mp.4000350 CrossRefPubMed

Rasch B, Papassotiropoulos A, de Quervain DF (2010) Imaging genetics of cognitive functions: focus on episodic memory. Neuroimage 53(3):870–877. https://doi.org/10.1016/j.neuroimage.2010.01.001 CrossRefPubMed

Raz N, Rodrigue KM, Kennedy KM, Head D, Gunning-Dixon F, Acker JD (2003) Differential aging of the human striatum: longitudinal evidence. Am J Neuroradiol 24(9):1849–1856PubMed

Raz N, Lindenberger U, Rodrigue KM, Kennedy KM, Head D, Williamson A, Dahle C, Gerstorf D, Acker JD (2005) Regional brain changes in aging healthy adults: general trends, individual differences and modifiers. Cereb Cortex 15(11):1676–1689. https://doi.org/10.1093/cercor/bhi044 CrossRefPubMed

Reeves S, Bench C, Howard R (2002) Ageing and the nigrostriatal dopaminergic system. Int J Geriatr psychiatry 17(4):359–370. https://doi.org/10.1002/gps.606 CrossRefPubMed

Rieckmann A, Karlsson S, Karlsson P, Brehmer Y, Fischer H, Farde L, Nyberg L, Bäckman L (2011) Dopamine D1 receptor associations within and between dopaminergic pathways in younger and elderly adults: links to cognitive performance. Cereb Cortex 21(9):2023–2032. https://doi.org/10.1093/cercor/bhq266 CrossRefPubMed

Salthouse TA, Babcock RL (1991) Decomposing adult age differences in working memory. Dev Psychol 27(5):763CrossRef

Shao W, Zhang S-z, Tang M, Zhang X-h, Zhou Z, Yin Y-q, Zhou Q-b, Huang Y-y, Liu Y-j, Wawrousek E, Chen T, Li S-b, Xu M, Zhou J-n, Hu G, Zhou J-w (2013) Suppression of neuroinflammation by astrocytic dopamine D2 receptors via alpha B-crystallin. Nature 494(7435):90–94. https://doi.org/10.1038/nature11748 CrossRefPubMed

Stein JL, Hibar DP, Madsen SK, Khamis M, McMahon KL, de Zubicaray GI, Hansell NK, Martin NG, Wright MJ, Saykin AJ, Jack CR Jr, Weiner MW, Toga AW, Thompson PM (2011) Genome-wide search reveals dopamine-related genetic variation effects on caudate volume replicated in young and elderly populations (N = 1198). Society for Neuroscience Abstract Viewer and Itinerary Planner 40

Taki Y, Thyreau B, Kinomura S, Sato K, Goto R, Wu K, Kawashima R, Fukuda H (2013) A longitudinal study of age- and gender-related annual rate of volume changes in regional gray matter in healthy adults. Hum Brain Mapp 34(9):2292–2301. https://doi.org/10.1002/hbm.22067 CrossRefPubMed

Thompson J, Thomas N, Singleton A, Piggott M, Lloyd S, Perry EK, Morris CM, Perry RH, Ferrier IN, Court JA (1997) D2 dopamine receptor gene (DRD2) Taq1 A polymorphism: reduced dopamine D2 receptor binding in the human striatum associated with the A1 allele. Pharmacogenetics 7(6):479–484CrossRefPubMed

Tsai SJ, Yu YWY, Lin CH, Chen TJ, Chen SP, Hong CJ (2002) Dopamine D2 receptor and N-methyl-d-aspartate receptor 2B subunit genetic variants and intelligence. Neuropsychobiology 45(3):128–130. https://doi.org/10.1159/000054951 CrossRefPubMed

Volkow ND, Gur RC, Wang G-J, Fowler JS, Moberg PJ, Ding Y-S, Hitzemann R, Smith G, Logan J (1998a) Association between decline in brain dopamine activity with age and cognitive and motor impairment in healthy individuals. Am J Psychiatry 155(3):344–349. https://doi.org/10.1176/ajp.155.3.344 PubMedCrossRef

Volkow ND, Wang GJ, Fowler JS, Ding YS, Gur RC, Gatley J, Logan J, Moberg PJ, Hitzemann R, Smith G, Pappas N (1998b) Parallel loss of presynaptic and postsynaptic dopamine markers in normal aging. Ann Neurol 44(1):143–147. https://doi.org/10.1002/ana.410440125 CrossRefPubMed

Wang Y, Chan GLY, Holden JE, Dobko T, Mak E, Schulzer M, Huser JM, Snow BJ, Ruth TJ, Calne DB, Stoessl AJ (1998) Age-dependent decline of dopamine D1 receptors in human brain: A PET study. Synapse 30 (1):56–61. https://doi.org/10.1002/(sici)1098-2396(199809)30:1<56::aid-syn7>3.0.co;2-jCrossRefPubMed

Watanabe K, Kakeda S, Yoshimura R, Ide S, Hayashi K, Katsuki A, Umene-Nakano W, Watanabe R, Abe O, Korogi Y (2015) Genetic variation in the catechol-O-Methyl transferase Val108/158Met Is linked to the caudate and posterior cingulate cortex volume in healthy subjects: voxel-based morphometry analysis of brain magnetic resonance imaging. Plos One. https://doi.org/10.1371/journal.pone.0142862 CrossRefPubMedPubMedCentral

Woodward ND, Zald DH, Ding ZH, Riccardi P, Ansari MS, Baldwin RM, Cowan RL, Li R, Kessler RM (2009) Cerebral morphology and dopamine D-2/D-3 receptor distribution in humans: a combined F-18 fallypride and voxel-based morphometry study. Neuroimage 46(1):31–38. https://doi.org/10.1016/j.neuroimage.2009.01.049 CrossRefPubMedPubMedCentral

Zazzo R (1974) Test des deux barrages. Actualités pédagogiques et psychologiques, vol 7. Delachaux et Nestlé, Neuchâtel

Title: Influence of the DRD2/ANKK1 Taq1A polymorphism on caudate volume in older adults without dementia
Authors: Xin Li
Goran Papenberg
Grégoria Kalpouzos
Lars Bäckman
Jonas Persson
Publication date: 01-07-2018
Publisher: Springer Berlin Heidelberg
Published in: Brain Structure and Function / Issue 6/2018
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-018-1650-0

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Influence of the DRD2/ANKK1 Taq1A polymorphism on caudate volume in older adults without dementia

Abstract

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

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