Abstract
Motivation is important for learning and cognition. Although dopaminergic (D2) transmission in the ventral striatum (VS) is associated with motivation, learning, and cognition are more strongly associated with function of the dorsal striatum, including activation in the caudate nucleus. A recent study found an interaction between intrinsic motivation and the DRD2/ANKK1 polymorphism (rs1800497), suggesting that A-carriers of rs1800497 are significantly more sensitive to motivation in order to improve during working memory (WM) training. Using data from the two large-scale imaging genetic data sets, IMAGEN (n=1080, age 13–15 years) and BrainChild (n∼300, age 6–27), we investigated whether rs1800497 is associated with WM. In the IMAGEN data set, we tested whether VS/caudate activation during reward anticipation was associated with WM performance and whether rs1800497 and VS/caudate activation interact to affect WM performance. We found that rs1800497 was associated with WM performance in IMAGEN and BrainChild. Higher VS and caudate activation during reward processing were significantly associated with higher WM performance (p<0.0001). An interaction was found between the DRD2/ANKK1 polymorphism rs1800497 and VS activation during reward anticipation on WM (p<0.01), such that carriers of the minor allele (A) showed a significant correlation between VS activation and WM, whereas the GG-homozygotes did not, suggesting that the effect of VS BOLD on WM is modified by inter-individual genetic differences related to D2 dopaminergic transmission.
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The other members of the IMAGEN consortium (http://www.imagen-europe.com) are: King’s College, Institute of Psychiatry, London, UK: L Reed, S Williams, A Lourdusamy, S Costafreda, A Cattrell, C Nymberg, L Topper, L Smith, S Havatzias, K Stueber, C Mallik, T-K Clarke, D Stacey, C Peng Wong, H Werts, S Williams, C Andrew, S Desrivieres, S Zewdie (Coordination office). Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité Universitätsmedizin Berlin, Berlin, Germany: A Heinz, I Häke, N Ivanov, A Klär, J Reuter, C Palafox, C Hohmann, C Schilling, K Lüdemann, A Romanowski, A Ströhle, E Wolff, M Rapp.Physikalisch-Technische Bundesanstalt, Berlin, Germany: B Ittermann, R Brühl, A Ihlenfeld, B Walaszek, F Schubert. Institute of Neuroscience, Trinity College, Dublin, Ireland: C Connolly, J Jones, E Lalor, E McCabe, A Ní Shiothchái. Department of Psychopharmacology, Central Institute of Mental Health, Mannheim, Germany: R Spanagel, F Leonardi-Essmann, W Sommer. Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Mannheim, Germany: S Vollstaedt-Klein. Department of Child and Adolescent Psychiatry, Central Institute of Mental Health, Mannheim, Germany: L Poustka, S Steiner. Department of Addictive Behaviour and Addiction, Medicine, Mannheim, Germany: M Buehler, S Vollstedt-Klein. Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany: E Stolzenburg, C Schmal, F Schirmbeck. Brain and Body Centre, University of Nottingham, Nottingham, UK: P Gowland, N Heym, C Lawrence, C Newman. Technische Universitaet Dresden, Dresden, Germany: T Huebner, S Ripke, E Mennigen, KU Muller, V Ziesch. Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany: U Bromberg, T Fadai, L Lueken, J Yacubian, J Finsterbusch. Institut National de la Santé et de la Recherche Médicale, Service Hospitalier Frédéric Joliot, Orsay, France: J-L Martinot, E Artiges, N Bordas, S de Bournonville, Z Bricaud, F Gollier Briand, H Lemaitre, J Massicotte, R Miranda, J Penttilä. Neurospin, Commissariat à l'Energie Atomique, Paris, France: A Barbot, Y Schwartz, C Lalanne, V Frouin, B Thyreau. Department of Experimental Psychology, Behavioural and Clinical Neurosciences Institute, University of Cambridge, Cambridge, UK: J Dalley, A Mar, N Subramaniam, D Theobald, N Richmond, M de Rover, A Molander, E Jordan, E Robinson, L Hipolata, M Moreno, Mercedes Arroyo. University of Sussex, Brighton, UK: D Stephens, T Ripley, H Crombag, Y Pena.Centre National de Genotypage, Evry, France (CNG): D Zelenika, S Heath. German Centre for Ethics in Medicine, Bonn (DZEM), Germany: D Lanzerath, B Heinrichs, T Spranger. Gesellschaft fuer Ablauforganisation m.b.H. (Munich) (GABO), Germany: B Fuchs, C Speiser. Klinik für Kinder- und Jugendpsychiatrie, Zentrum für Psychosoziale Medizin, Universitätsklinikum Heidelberg, Germany: F Resch, J Haffner, P Parzer, R Brunner. Scito, Paris, France: A Klaassen, I Klaassen. PERTIMM, Asnières-Sur-Seine, France: P Constant, X Mignon. NordicNeuroLabs, Bergen, Norway: T Thomsen, S Zysset, A Vestboe. Delosis Ltd, London, UK: J Ireland, J Rogers.
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Nymberg, C., Banaschewski, T., Bokde, A. et al. DRD2/ANKK1 Polymorphism Modulates the Effect of Ventral Striatal Activation on Working Memory Performance. Neuropsychopharmacol 39, 2357–2365 (2014). https://doi.org/10.1038/npp.2014.83
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DOI: https://doi.org/10.1038/npp.2014.83
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