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The executive function of shifting between mental sets demands cognitive flexibility. Based on evidence that physical exercise fostered cognition, we tested whether acute physical exercise can improve shifting in an unselected sample of adolescents. Genetic polymorphisms were analyzed to gain more insight into possibly contributing neurophysiological processes. We examined 297 students aged between 13 and 17 years in their schools. Physical exercise was manipulated by an intense incremental exercise condition using bicycle ergometers and a control condition which involved watching an infotainment cartoon while sitting calm. The order of conditions was counterbalanced between participants. Shifting was assessed by a switching task after both conditions. Acute intense physical exercise significantly improved shifting as indicated by reduced switch costs. Exercise-induced performance gains in switch costs were predicted by a single nucleotide polymorphism (SNP) targeting the Dopamine Transporter (DAT1/SLCA6A3) gene suggesting that the brain dopamine system contributed to the effect. The results demonstrate the potential of acute physical exercise to improve cognitive flexibility in adolescents. The field conditions of the present approach suggest applications in schools.

There is converging evidence for genetic, biochemical, and neuropsychological factors to increase the risk for anxiety and anxiety disorders. The pathogenesis of anxiety disorders is assumed to be influenced by a complex interaction of these individual risk factors on several levels, affecting intermediate phenotypes of anxiety such as the startle reflex. Thus, in the present double-blind, placebocontrolled study we attempted to paradigmatically investigate a multi-level pathogenetic model of anxiety by testing the effect of 300 mg caffeine citrate as an antagonist at the adenosine A2A receptor vs placebo on the emotion-potentiated (unpleasant, neutral, and pleasant International Affective Picture System pictures) startle reflex in 110 healthy individuals (male ¼ 56, female ¼ 54) stratified for the adenosine A2A receptor (ADORA2A) 1976T4C polymorphism (rs5751876). In addition to the expected main effect of picture category (highest startle amplitude for unpleasant, lowest for pleasant pictures) groups across all ADORA2A 1976T4C genotype and intervention (caffeine vs placebo) groups, an interaction effect of genotype, intervention, and picture category was discerned: In ADORA2A 1976TT risk genotype carriers, highest startle magnitudes were observed after caffeine administration in response to unpleasant pictures, with this effect arising particularly from the female subgroup. Our data point to a complex, multi-level, and potentially gender-specific pathogenetic model of anxiety, with genetic and biochemical factors interactively increasing the risk of maladaptive emotional processing and thereby possibly also anxiety disorders. The present findings may eventually aid in improving primary and secondary prevention by sharpening the risk profiles of anxiety-prone individuals.