Serotonergic Modulation of Cognition, Emotion and Brain Activation in Healthy Volunteers
NCT ID: NCT04239339
Last Updated: 2023-11-18
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE4
66 participants
INTERVENTIONAL
2020-04-28
2022-10-30
Brief Summary
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* To apply a pharmacological tool of selective serotonin (5-hydroxytryptamine, 5-HT system) reuptake inhibition in healthy humans. Specifically:
* To investigate how sub-chronic administration of 20 mg of escitalopram affects cognitive performance ('cold' cognition) and social-emotional functioning ('hot' cognition) compared with placebo; and
* To investigate how sub-chronic administration of 20 mg of escitalopram affects functional brain activation during a paradigm of reinforcement learning following drug administration compared with placebo, and how activation relates to cognitive performance and social-emotional functioning.
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Detailed Description
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* To apply a pharmacological tool of selective serotonin (5-hydroxytryptamine, 5-HT system) reuptake inhibition in healthy humans. Specifically:
* To investigate how sub-chronic administration of 20 mg of escitalopram affects cognitive performance ('cold' cognition) and social-emotional functioning ('hot' cognition) compared with placebo; and
* To investigate how sub-chronic administration of 20 mg of escitalopram affects functional brain activation during a paradigm of reinforcement learning following drug administration compared with placebo, and how activation relates to cognitive performance and social-emotional functioning.
Serotonin is a monoamine neurotransmitter implicated in diverse cognitive and affective brain functions. Serotonin has a significant role in the regulation of cognition and mood, including emotional appraisal, perception and flexible behaviour, with 5-HT receptors found in the cortex, amygdala and hippocampus. The investigators have previously shown that in healthy human experimental studies, acute dietary tryptophan depletion induces 'waiting' impulsivity and impulsive behaviours, impairs goal-directed behaviour and shifts behavioural control toward habitual responding when appetitive, but goal-directed when aversive. Reduced availability of forebrain serotonin has also shown to impair a range of cognitive processes, such as psychomotor processing, episodic memory, attention and executive function. Recently, the research team have shown that using an acute and clinically relevant dose (20 mg) of escitalopram impaired learning and cognitive flexibility, but improved response inhibition in healthy humans, suggesting a dissociation of effects possibly mediated by differential modulation of brain serotonin levels in distinct functional neural circuits.
The investigators now aim to investigate the effects of sub-chronic administration of 20 mg of escitalopram (i.e. three weeks) in healthy volunteers using sophisticated neuropsychological testing (Cambridge Neuropsychological Test Automated Battery and EMOTICOM) and functional magnetic resonance imaging (fMRI). Whereas 'cold' cognition refers to the use of non-emotional processing (e.g. episodic memory; spatial working memory), 'hot' cognition is emotion-laden and used in response to stimuli with affective salience (e.g. decision-making under high levels of risk of uncertainty). It has been suggested that cognitive-emotional effects, such as the re-appraisal and re-evaluation of emotions underlying learning mechanisms, may mediate improvements in mood associated with SSRI treatment. This project will help further the understanding of the role of serotonin in the regulation of cognitive and emotional processes, as well the neural correlates underlying reinforcement learning, in healthy humans.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
BASIC_SCIENCE
TRIPLE
Study Groups
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Control Group
The placebo control group will be administered the exact same procedure as the intervention group, the only difference being that this group will be administered a placebo pill.
Placebo
Placebo daily for approximately 3 weeks.
Intervention Group
The intervention group will be administered 20mg of Escitalopram daily for approximately 3 weeks.
Escitalopram 20 mg
20mg daily for approximately 3 weeks.
Interventions
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Escitalopram 20 mg
20mg daily for approximately 3 weeks.
Placebo
Placebo daily for approximately 3 weeks.
Eligibility Criteria
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Inclusion Criteria
Exclusion Criteria
* Current or previous neurological disease, severe somatic disease, or the consumption of drugs likely to influence the test results.
* Non- fluent in Danish or pronounced visual or auditory impairments.
* Current or past learning disability.
* Pregnancy (females).
* Lactation (females).
* Contraindications for MRI (pacemaker, metal implants, etc.).
* Allergy to the ingredients in the administered drug.
* Abnormal ECG (e.g. prolonged QT syndrome).
* Dizzy when changing from supine to upright position (e.g. postural orthostatic tachycardia syndrome).
* Mild hypotension (blood pressure below 100/70 mmHg) or hypertension (blood pressure above 140/90 mmHg).
* Head injury or concussion resulting in loss of consciousness for more than 2 min.
* Alcohol or drug abuse.
* Drug use other than tobacco and alcohol within the last 30 days.
* Hash \> 50 x lifetime.
* Drugs \> 10 x lifetime (for each substance).
* Nicotine addiction.
* Current psychoactive medication.
* Severe physical impairments affecting eyesight or motor performance.
* Hamilton-6 depression scale score \> 5.
18 Years
45 Years
ALL
Yes
Sponsors
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University of Cambridge
OTHER
Lundbeck Foundation
OTHER
Rigshospitalet, Denmark
OTHER
Responsible Party
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Professor Barbara Jacquelyn Sahakian
Professor
Locations
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Neurobiology Research Unit
Copenhagen, , Denmark
Countries
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References
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Homberg JR. Serotonin and decision making processes. Neurosci Biobehav Rev. 2012 Jan;36(1):218-36. doi: 10.1016/j.neubiorev.2011.06.001. Epub 2011 Jun 12.
Meneses A. Are 5-HT(1B/1D) and 5-HT(2A/2B/2C) receptors involved in learning and memory processes? IDrugs. 1999 Aug;2(8):796-801.
Worbe Y, Savulich G, Voon V, Fernandez-Egea E, Robbins TW. Serotonin depletion induces 'waiting impulsivity' on the human four-choice serial reaction time task: cross-species translational significance. Neuropsychopharmacology. 2014 May;39(6):1519-26. doi: 10.1038/npp.2013.351. Epub 2014 Jan 2.
Worbe Y, Savulich G, de Wit S, Fernandez-Egea E, Robbins TW. Tryptophan Depletion Promotes Habitual over Goal-Directed Control of Appetitive Responding in Humans. Int J Neuropsychopharmacol. 2015 Feb 5;18(10):pyv013. doi: 10.1093/ijnp/pyv013.
Worbe Y, Palminteri S, Savulich G, Daw ND, Fernandez-Egea E, Robbins TW, Voon V. Valence-dependent influence of serotonin depletion on model-based choice strategy. Mol Psychiatry. 2016 May;21(5):624-9. doi: 10.1038/mp.2015.46. Epub 2015 Apr 14.
Park SB, Coull JT, McShane RH, Young AH, Sahakian BJ, Robbins TW, Cowen PJ. Tryptophan depletion in normal volunteers produces selective impairments in learning and memory. Neuropharmacology. 1994 Mar-Apr;33(3-4):575-88. doi: 10.1016/0028-3908(94)90089-2.
Sahakian BJ, Morris RG, Evenden JL, Heald A, Levy R, Philpot M, Robbins TW. A comparative study of visuospatial memory and learning in Alzheimer-type dementia and Parkinson's disease. Brain. 1988 Jun;111 ( Pt 3):695-718. doi: 10.1093/brain/111.3.695.
Bland AR, Roiser JP, Mehta MA, Schei T, Boland H, Campbell-Meiklejohn DK, Emsley RA, Munafo MR, Penton-Voak IS, Seara-Cardoso A, Viding E, Voon V, Sahakian BJ, Robbins TW, Elliott R. EMOTICOM: A Neuropsychological Test Battery to Evaluate Emotion, Motivation, Impulsivity, and Social Cognition. Front Behav Neurosci. 2016 Feb 24;10:25. doi: 10.3389/fnbeh.2016.00025. eCollection 2016.
Armand S, Langley C, Johansen A, Ozenne B, Overgaard-Hansen O, Larsen K, Jensen PS, Knudsen GM, Sahakian BJ, Stenbaek DS, Fisher PM. Functional brain responses to emotional faces after three to five weeks of intake of escitalopram in healthy individuals: a double-blind, placebo-controlled randomised study. Sci Rep. 2024 Feb 7;14(1):3149. doi: 10.1038/s41598-024-51448-2.
Langley C, Armand S, Luo Q, Savulich G, Segerberg T, Sondergaard A, Pedersen EB, Svart N, Overgaard-Hansen O, Johansen A, Borgsted C, Cardinal RN, Robbins TW, Stenbaek DS, Knudsen GM, Sahakian BJ. Chronic escitalopram in healthy volunteers has specific effects on reinforcement sensitivity: a double-blind, placebo-controlled semi-randomised study. Neuropsychopharmacology. 2023 Mar;48(4):664-670. doi: 10.1038/s41386-022-01523-x. Epub 2023 Jan 23.
Other Identifiers
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H-18038352
Identifier Type: -
Identifier Source: org_study_id
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