PT  - JOURNAL ARTICLE
AU  - Roberto Viviani
AU  - Irene Messina
AU  - Julia E. Bosch
AU  - Lisa Dommes
AU  - Anna Paul
AU  - Katharina L. Schneider
AU  - Catharina Scholl
AU  - Julia C. Stingl
TI  - Effects of genetic variability of CYP2D6 on neural substrates of sustained attention during on-task activity
AID  - 10.1101/831198
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 831198
4099  - http://biorxiv.org/content/early/2020/10/09/831198.short
4100  - http://biorxiv.org/content/early/2020/10/09/831198.full
AB  - The polymorphic drug-metabolizing enzyme CYP2D6, which is responsible for the metabolism of most psychoactive compounds, is expressed not only in the liver, but also in the brain. The effects of its marked genetic polymorphism on the individual capacity to metabolize drugs are well known, but its role in metabolism of neural substrates affecting behavior personality or cognition, suggested by its CNS expression, is a long-standing unresolved issue. To verify earlier findings suggesting a potential effect on attentional processes, we collected functional imaging data while N=415 participants performed a simple task in which the reward for correct responses varied. CYP2D6 allelic variants predicting higher levels of enzymatic activity level were positively associated with cortical activity in occipito-parietal areas as well as in a right lateralized network known to be activated by spatial attentional tasks. Reward-related modulation of activity in cortical areas was more pronounced in poor metabolizers. In conjunction with effects on reaction times, our findings provide evidence for reduced cognitive efficiency in rapid metabolizers compared to poor metabolizers in on-task attentional processes manifested through differential recruitment of a specific neural substrate.Competing Interest StatementThe authors have declared no competing interest.