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

Last updated: December 13, 2024
Sponsor: Rigshospitalet, Denmark
Overall Status: Active - Not Recruiting

Phase

4

Condition

Kleptomania

Panic Disorders

Anxiety Disorders

Treatment

Placebo oral tablet

Escitalopram

Clinical Study ID

NCT04336228
H-18038325
  • Ages 18-70
  • All Genders
  • Accepts Healthy Volunteers

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Individuals with high scores on obsessive-compulsive traits (with or without adiagnosis of OCD established by a psychiatrist) and healthy volunteers (male orfemale) between 18 and 70 years. Compulsive individuals without an OCD diagnosis areindividuals without a history of psychiatric or other major medical conditions butscoring abnormally high on the Obsessive-Compulsive Inventory (OCI) questionnaire.

Exclusion

Exclusion Criteria:

  • Current or previous neurological disease, severe somatic disease, or consumption ofmedical drugs likely to influence the test results

  • Non- fluent in Danish or pronounced visual or auditory impairments

  • Current or past learning disability.

  • Pregnancy

  • Lactation

  • Participation in experiments with radioactivity (> 10 mSv) within the last year orsignificant occupational exposure to radioactivity.

  • 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 orthostatictachycardia syndrome).

  • Mild hypotension (blood pressure below 100/70 mmHg) or hypertension (blood pressureabove 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).

  • Current medication with serotonergic acting compounds. Use of other psychoactivesubstances must be stable at least one month prior to inclusion and maintainedthroughout the study.

  • Severe physical impairments affecting eyesight or motor performance.

  • For the OCD group: other Axis I mental disorder as primary diagnosis according toICD-10 criteria.

  • For healthy volunteers: any current or former primary psychiatric disorder (Axis IWHO ICD-10 diagnostic classification).

Study Design

Total Participants: 46
Treatment Group(s): 2
Primary Treatment: Placebo oral tablet
Phase: 4
Study Start date:
April 01, 2020
Estimated Completion Date:
December 31, 2027

Study 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.

Connect with a study center

  • Neurobiology Research Unit, Rigshospitalet

    Copenhagen, 2100
    Denmark

    Site Not Available

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