Serotonergic modulation of cognition
University of Cambridge
Psychiatry, School of clinical medicine
Doctor of Philosophy (PhD)
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Skandali, N. (2018). Serotonergic modulation of cognition (Doctoral thesis). https://doi.org/10.17863/CAM.25255
Action control arises from the interaction of two anatomically distinct decision-making systems, namely goal-directed and habitual behaviour. Goal-directed behaviour is characterized by the consideration of future choices and respective outcomes whereas habitual responding is driven by stimulus-response associations. Response inhibition is essential for goal-directed behaviour and deficits are shown in impulsivity. We administered an acute clinically relevant dosage of the commonly used serotonin reuptake inhibitor escitalopram to sixty-six healthy volunteers in a double-blind, randomized, placebo-controlled design. We administered a large task battery in order to study the effect of escitalopram in several cognitive functions including response inhibition, learning and affective processing. We found dissociate effects on cognitive aspects possibly mediated by distinct cortico-striatal loops. Acute escitalopram administration had a beneficial effect on action cancellation, one aspect of inhibitory control, without any effect on action restraint or waiting impulsivity. The treatment resulted in impaired performance in a probabilistic reversal-learning task and increased sensitivity to misleading feedback thus leading to maladaptive performance. An extra-dimensional set shift impairment during an attention set shift task and a tendency towards impaired instrumental learning discrimination were also observed in the escitalopram group. Our results are discussed in the context of well-documented effects of the dopaminergic system and suggestions of opponent interaction of serotonin and dopamine.
serotonin, reinforcement learning, response inhibition, cognition, goal directed learning, habits, emotional processing, neuropsychopharmacology, neuropsychiatry
This work was jointly sponsored by the University of Cambridge and Cambridgeshire and Peterborough NHS Foundation Trust and approved by the NHS East of England - Cambridge Central Research Ethics Committee (REC reference: 15/EE/0004). It was 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). A Medical Research Council (MRC) Doctoral grant studentship was awarded to Dr N Skandali (1432057).
This record's DOI: https://doi.org/10.17863/CAM.25255
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