The Role of Serotonin in Compulsive Behavior in Humans: Underlying Brain Mechanisms
Status and phase
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Treatments
Details and patient eligibility
About
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.
Full 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.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
- Individuals with high scores on obsessive-compulsive traits (with or without a diagnosis of OCD established by a psychiatrist) and healthy volunteers (male or female) between 18 and 70 years. Compulsive individuals without an OCD diagnosis are individuals without a history of psychiatric or other major medical conditions but scoring abnormally high on the Obsessive-Compulsive Inventory (OCI) questionnaire.
Exclusion criteria
- Current or previous neurological disease, severe somatic disease, or consumption of medical 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 or significant 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 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).
- Current medication with serotonergic acting compounds. Use of other psychoactive substances must be stable at least one month prior to inclusion and maintained throughout the study.
- Severe physical impairments affecting eyesight or motor performance.
- For the OCD group: other Axis I mental disorder as primary diagnosis according to ICD-10 criteria.
- For healthy volunteers: any current or former primary psychiatric disorder (Axis I WHO ICD-10 diagnostic classification).
Trial design
Primary purpose
Allocation
Interventional model
Masking
46 participants in 4 patient groups, including a placebo group
Trial contacts and locations
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Central trial contact
Gitte M. Knudsen, Professor; Trevor W. Robbins, Professor
Data sourced from clinicaltrials.gov
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