The Role of Serotonin in Compulsive Behavior in Humans: Underlying Brain Mechanisms
Last updated on July 2021Recruitment
- Recruitment Status
- Recruiting
- Estimated Enrollment
- Same as current
Summary
- Conditions
- Healthy Individuals
- Obsessive Compulsive Disorder
- Type
- Interventional
- Phase
- Phase 4
- Design
- Allocation: RandomizedIntervention Model: Parallel AssignmentMasking: Triple (Participant, Investigator, Outcomes Assessor)Primary Purpose: Basic Science
Participation Requirements
- Age
- Between 18 years and 70 years
- Gender
- Both males and females
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 punis...
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.
Tracking Information
- NCT #
- NCT04336228
- Collaborators
- University of Cambridge
- Lundbeck Foundation
- Investigators
- Study Chair: Gitte M. Knudsen, Professor Neurobiology Research Unit, Rigshospitalet