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

Healthy Individuals Clinical Trial

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

Status Recruiting

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Compulsive Behavior
• Healthy Individuals
• Obsessive-Compulsive Disorder

• NCT number: NCT04336228
• Study type: Interventional
• Source: Rigshospitalet, Denmark
• Contact: Gitte M. Knudsen, Professor
• Phone: +45 35456720
• Email: gitte@nru.dk
• Status: Recruiting
• Phase: Phase 4
• Start date: April 1, 2020
• Completion date: August 2024