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Neuropsychopharmacology. 2014 Sep;39(10):2357-65. doi: 10.1038/npp.2014.83. Epub 2014 Apr 9.

DRD2/ANKK1 polymorphism modulates the effect of ventral striatal activation on working memory performance.

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Department of Neuroscience, Karolinska institute, Stockholm, Sweden.
1] Department of Child and Adolescent Psychiatry, Central Institute of Mental Health, Mannheim, Germany [2] Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Institute of Neuroscience and Discipline of Psychiatry, School of Medicine, Trinity College Dublin, Dublin, Ireland.
Department of Systems Neuroscience, Universitaetsklinikum Hamburg Eppendorf, Hamburg, Germany.
1] Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK [2] Department of Psychiatry, Universite de Montreal, CHU Ste Justine Hospital, Montreal, QC, Canada.
Neurospin, Commissariat à l'Energie Atomique et aux Energies Alternatives, Paris, France.
1] Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland [2] Departments of Psychiatry and Psychology, University of Vermont, Burlington, Vermont, USA.
School of Physics and Astronomy, University of Nottingham, Nottingham, UK.
Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Physikalisch-Technische Bundesanstalt (PTB), Braunschweig und Berlin, Berlin, Germany.
Department of Addictive Behaviour and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
1] Institut National de la Santé et de la Recherche Médicale, INSERM CEA Unit 1000 'Imaging & Psychiatry', University Paris Sud, Orsay, France [2] AP-HP Department of Adolescent Psychopathology and Medicine, Maison de Solenn, University Paris Descartes, Paris, France.
1] Rotman Research Institute, University of Toronto, Toronto, Canada [2] School of Psychology, University of Nottingham, Nottingham, UK [3] Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
The Hospital for Sick Children, University of Toronto, Toronto, Canada.
Department of Experimental Psychology, Behavioural and Clinical Neurosciences Institute, University of Cambridge, Cambridge, UK.
Department of Psychiatry and Psychotherapy, Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.
Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK.


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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