title: Dopamine and glutamate receptor genes interactively influence episodic memory in old age.
abstract: Both the dopaminergic and glutamatergic systems modulate episodic memory consolidation. Evidence from animal studies suggests that these two neurotransmitters may interact in influencing memory performance. Given that individual differences in episodic memory are heritable, we investigated whether variations of the dopamine D2 receptor gene (rs6277, C957T) and the N-methyl-D-aspartate 3A (NR3A) gene, coding for the N-methyl-D-aspartate 3A subunit of the glutamate N-methyl-D-aspartate receptor (rs10989591, Val362Met), interactively modulate episodic memory in large samples of younger (20-31 years; n = 670) and older (59-71 years; n = 832) adults. We found a reliable gene-gene interaction, which was observed in older adults only: older individuals carrying genotypes associated with greater D2 and N-methyl-D-aspartate receptor efficacy showed better episodic performance. These results are in line with findings showing magnification of genetic effects on memory in old age, presumably as a consequence of reduced brain resources. Our findings underscore the need for investigating interactive effects of multiple genes to understand individual difference in episodic memory.
authors: Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany; Aging Research Center, Karolinska Institute and Stockholm University, Stockholm, Sweden. Electronic address: goran.papenberg@ki.se.
authors: Goran
authors: G
authors: Papenberg
authors: Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany; Department of Psychology, Technische Universität Dresden, Dresden, Germany.
authors: Shu-Chen
authors: SC
authors: Li
authors: Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany; Department of Education and Psychology, Freie Universität Berlin, Berlin, Germany.
authors: Irene E
authors: IE
authors: Nagel
authors: Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors: Wilfried
authors: W
authors: Nietfeld
authors: Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors: Brit-Maren
authors: BM
authors: Schjeide
authors: Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany; Charité Research Group on Geriatrics, Charité-Universitätsmedizin, Berlin, Germany.
authors: Julia
authors: J
authors: Schröder
authors: Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors: Lars
authors: L
authors: Bertram
authors: Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany; Department of Education and Psychology, Freie Universität Berlin, Berlin, Germany.
authors: Hauke R
authors: HR
authors: Heekeren
authors: Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany.
authors: Ulman
authors: U
authors: Lindenberger
authors: Aging Research Center, Karolinska Institute and Stockholm University, Stockholm, Sweden.
authors: Lars
authors: L
authors: Bäckman
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics* / Q000523:psychology*; D004298:Dopamine / Q000502:physiology; D004843:Epistasis, Genetic / Q000502:physiology*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D018698:Glutamic Acid / Q000502:physiology; D006801:Humans; D008297:Male; D061212:Memory, Episodic; D008875:Middle Aged; D018377:Neurotransmitter Agents / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000235:genetics* / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics* / Q000502:physiology*; D055815:Young Adult
chemical_list: C464437:NR3A NMDA receptor; D018377:Neurotransmitter Agents; D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D004298:Dopamine
keywords: Aging; D2 receptors; Dopamine; Episodic memory; Gene-gene interactions; Glutamate; NMDA receptors