Serotonin is implicated in multiple executive functions including goal-directed learning, cognitive flexibility, response inhibition and emotional regulation. These functions are impaired in several psychiatric disorders, such as depression and obsessive-compulsive disorder. We tested the cognitive effects of the selective serotonin reuptake inhibitor escitalopram, using an acute and clinically relevant dose (20 mg), in 66 healthy male and female volunteers in a double-blind, placebo-controlled study. Participants performed a cognitive test battery including a probabilistic and reversal learning task, the CANTAB intra-dimensional/extra-dimensional shift test of cognitive flexibility, a response inhibition task with interleaved stop-signal and No-Go trials and tasks measuring emotional processing. We showed that acute escitalopram administration impaired learning and cognitive flexibility, but improved the ability to inhibit responses in stop-signal trials while leaving unaffected acute emotional processing. Our findings suggest a dissociation of effects of acute escitalopram on cognitive functions, possibly mediated by differential modulation of brain serotonin levels in distinct functional neural circuits.This work was supported by a Wellcome Trust Senior Investigator Award to TW Robbins (104631/Z/14/Z) and by the NIHR Cambridge Biomedical Research Centre (Mental Health theme). NS was supported by a Medical Research Council Doctoral Grant Studentship (1432057), JBR by the Wellcome Trust (103838), VV by a Medical Research Council Senior Fellowship (MR/P008747/1), SCR by a Wellcome Trust Clinical Fellowship (110049/Z/15/Z), LP by the Medical Research Council (MR/P01271X/1) and FC employed by Cambridge Cognition. JBR received research grants unrelated to this work from Medical Research Council, James S McDonnell Foundation, PSPAssociation, AZ-Medimmune, Janssen and Lilly, and served as editor for Brain. RR received a grant (16KNO16238) by the Federal Ministry for Economic Affairs and Energy. BJS Consults for Cambridge Cognition, PEAK and Mundipharma, SRC for Cambridge Cognition and Shire, and TWR for Cambridge Cognition, Mundipharma and Unilever, has held research grants from Shionogi and Lundbeck and receives Royalties for CANTAB
