Interactive effects of dopamine transporter genotype and aging on resting-state functional networks

PLoS One. 2019 May 8;14(5):e0215849. doi: 10.1371/journal.pone.0215849. eCollection 2019.


Aging and dopamine modulation have both been independently shown to influence the functional connectivity of brain networks during rest. Dopamine modulation is known to decline during the course of aging. Previous evidence also shows that the dopamine transporter gene (DAT1) influences the re-uptake of dopamine and the anyA9 genotype of this gene is associated with higher striatal dopamine signaling. Expanding these two lines of prior research, we investigated potential interactive effects between aging and individual variations in the DAT1 gene on the modular organization of brain acvitiy during rest. The graph-theoretic metrics of modularity, betweenness centrality and participation coefficient were assessed in 41 younger (age 20-30 years) and 37 older (age 60-75 years) adults. Age differences were only observed in the participation coefficient in carriers of the anyA9 genotype of the DAT1 gene and this effect was most prominently observed in the default mode network. Furthermore, we found that individual differences in the values of the participation coefficient correlated with individual differences in fluid intelligence and a measure of executive control in the anyA9 carriers. The correlation between participation coefficient and fluid intelligence was mainly shared with age-related differences, whereas the correlation with executive control was independent of age. These findings suggest that DAT1 genotype moderates age differences in the functional integration of brain networks as well as the relation between network characteristics and cognitive abilities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aging / genetics*
  • Aging / physiology*
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Brain / physiology
  • Brain Mapping
  • Cognition
  • Dopamine Plasma Membrane Transport Proteins / genetics*
  • Female
  • Genotype*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Nerve Net / diagnostic imaging
  • Nerve Net / metabolism
  • Nerve Net / physiology*
  • Rest / physiology*
  • Young Adult


  • Dopamine Plasma Membrane Transport Proteins
  • SLC6A3 protein, human

Grants and funding

This research was supported by 2 grants from the German Research Foundation (DFG LI 879/12-2 and DFG SFB 940/2, Project B3) both awarded to SCL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.