NCT04336228

The Role of Serotonin in Compulsive Behavior in Humans: Underlying Brain Mechanisms

• Status: Active Not Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 46 (actual)
• Sponsor: Rigshospitalet, Denmark · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Accepted

Summary

The aim of this project is to investigate: * The status of the central serotonin (5-hydroxytryptamine, 5-HT) system in compulsive behaviour and how it is affected by sub-chronic escitalopram administration * The mechanisms underlying how sub-chronic administration of escitalopram affects the central 5-HT system * How changes in cognitive performance, including the balance between habitual and goal-directed mechanisms, are affected in compulsive behaviour by boosting 5-HT function * How functional brain changes in cognitive function measured with magnetic resonance imaging relate to altered 5-HT function following escitalopram administration.

Detailed description

Previous studies have shown that 5-HT is strongly implicated in compulsive behaviours in experimental animals. Manipulation of 5-HT influences neuronal interactions underlying action selection. Reduced forebrain 5-HT causes perseveration and impairs goal-directed behaviour under reward but not punishment. Dysfunctional 5-HT neurotransmission has also been implicated in Obsessive-Compulsive Disorder (OCD) based on the selective efficacy of relatively high doses of selective serotonin reuptake inhibitors (SSRIs) in treating this disorder. Hitherto, it is unknown whether there is a primary defect in the serotonergic system or whether SSRIs ameliorate symptoms by modulating other brain neurotransmitter pathways. So far, only one study of central 5-HT release in OCD patients has been conducted and its methodology may be questioned. A number of behavioural and cognitive features of OCD, including endophenotype markers that appear to characterise the disorder have been determined. These include a shift in cognitive control from a goal-directed strategy to a habitual (stimulus-response, S-R) strategy, cognitive rigidity in terms of both reversal learning and attentional set-shifting, impaired response inhibition and planning, and a tendency to over-respond to spurious negative feedback in a probabilistic learning paradigm. Neural substrates of these deficits are being investigated using brain imaging methodologies based on magnetic resonance and preliminary evidence suggests an over-active medial prefrontal cortex-caudate nucleus circuits and underactive lateral prefrontal cortex-putamen circuits. However, little evidence exists that relates to the hypothesis of an over-active habit system in this disorder or to the role of serotonin in all these cognitive and behavioural deficits observed in OCD and compulsivity in general.

Conditions

• Obsessive-Compulsive Disorder/High Compulsive Individuals
• Healthy Individuals

Interventions

Type	Name	Description
DRUG	Escitalopram	20mg daily for 3-4 weeks.
DRUG	Placebo oral tablet	20mg placebo tablet daily for 3-4 weeks.

Timeline

• Start date: 2020-04-01
• Primary completion: 2027-12-31
• Completion: 2027-12-31
• First posted: 2020-04-07
• Last updated: 2024-12-18

Locations

1 site across 1 country: Denmark