Genetic determinants of cognitive responses to caffeine drinking identified from a double-blind, randomized, controlled trial

Eur Neuropsychopharmacol. 2015 Jun;25(6):798-807. doi: 10.1016/j.euroneuro.2015.03.001. Epub 2015 Mar 16.

Abstract

The widely observed between-subject variability in cognitive responses to coffee may have a genetic basis. We evaluated cognitive responses to caffeine throughout three complex cognitive tasks assessing different subdomains of attention, namely Alerting and Orienting (Categorical Search Task) and Executive Control (Stroop Task and Eriksen Flanker Task). We explored whether they are influenced by gene variants affecting adenosine metabolism or catecholamine receptors. We recruited 106 healthy male subjects who were administered, in a double-blind design, 40mL of either a decaffeinated coffee preparation plus 3mg/kg caffeine (caf) or the corresponding vehicle (decaf). The protocol was repeated 24h later with the alternative preparation. Cognitive tasks were performed between 30min and 2h after caf or decaf administration. Each subject underwent ambulatory blood pressure monitoring for 2h. Blood samples were collected for genetic evaluations and for plasma caffeine and catecholamines measures. We found a significant reduction of reaction times in two of the cognitive tasks (Categorical Search Task and Stroop Task) after caf compared with decaf, indicating that caffeine, on average, improved the attention level in the domains under investigation. We also found, however, a great inter-individual variability in the cognitive performance responses to caffeine. In exploring genetic sources for such variability, we found a relation between polymorphisms of adenosine A2A and the caffeine effects on the attentional domains of Orienting and Executive control. In conclusion, variability in the attentional response to coffee may be partly explained by genetic polymorphisms of adenosine and adrenergic receptors.

Keywords: Attention; Caffeine; Coffee; Cognitive responses; Nutrigenetics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Attention / drug effects*
  • Attention / physiology
  • Beverages
  • Blood Pressure / drug effects
  • Blood Pressure / genetics
  • Caffeine / metabolism
  • Caffeine / pharmacology*
  • Central Nervous System Stimulants / metabolism
  • Central Nervous System Stimulants / pharmacology*
  • Double-Blind Method
  • Executive Function / drug effects*
  • Executive Function / physiology
  • Female
  • Genotype
  • Humans
  • Male
  • Neuropsychological Tests
  • Orientation / drug effects*
  • Orientation / physiology
  • Polymorphism, Single Nucleotide / genetics*
  • Prospective Studies
  • Reaction Time / drug effects
  • Reaction Time / genetics
  • Receptor, Adenosine A2A / genetics*
  • Time Factors
  • Young Adult

Substances

  • Central Nervous System Stimulants
  • Receptor, Adenosine A2A
  • Caffeine