title: Aging magnifies the effects of dopamine transporter and D2 receptor genes on backward serial memory.
abstract: Aging compromises dopamine transporter (DAT) and receptor mechanisms in the frontostriatal circuitry. In a sample of 1288 younger and older adults, we investigated (i) whether individual differences in genotypes of the DAT gene (i.e., SLC6A3, the DAT variable number of tandem repeat 9/9, 9/10, and 10/10) and in the D2 receptor (DRD2) gene (i.e., the C957T [rs6277] CC and any T) interactively contribute to phenotype variations in episodic memory performance; and (ii) whether these genetic effects are magnified in older adults, because of considerable declines in the dopamine functions. Our results showed that carrying genotypes associated with higher levels of striatal synaptic dopamine (DAT 9/9) and higher density of extrastriatal D2 receptors (C957T CC) were associated with better backward serial recall, an episodic memory task with high encoding and retrieval demands. Critically, the gene-gene interaction effect was reliably stronger in older than in younger adults. In line with the resource modulation hypothesis, our findings suggest that aging-related decline in brain phenotypes (e.g., dopamine functions) could alter the relations between genotypes and behavioral phenotypes (e.g., episodic memory).
authors.affiliation: Max Planck Institute for Human Development, Center for Lifespan Psychology, Berlin, Germany. li@psychologie.tu-dresden.de
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Li
authors.forename: Goran
authors.initials: G
authors.lastname: Papenberg
authors.forename: Irene E
authors.initials: IE
authors.lastname: Nagel
authors.forename: Claudia
authors.initials: C
authors.lastname: Preuschhof
authors.forename: Julia
authors.initials: J
authors.lastname: Schröder
authors.forename: Wilfried
authors.initials: W
authors.lastname: Nietfeld
authors.forename: Lars
authors.initials: L
authors.lastname: Bertram
authors.forename: Hauke R
authors.initials: HR
authors.lastname: Heekeren
authors.forename: Ulman
authors.initials: U
authors.lastname: Lindenberger
authors.forename: Lars
authors.initials: L
authors.lastname: Bäckman
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology*; D008875:Middle Aged; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D017448:Receptors, Dopamine D2