The Role of Dopamine, Reward Learning and Prefrontal Activity in Expectation-induced Mood Enhancement

NCT05208294 | Completed

• 1 other identifier: CRC 289 Projekt A07
• Study Type: interventional
• Target: 297
• Locations: 1 country
• Sites: 1

Brief Summary

Although placebo effects on depressive symptoms are well documented, the underlying mechanisms and moderating factors of expectation effects on mood and depression are poorly understood. Various studies show reduced reward processing in clinical and subclinical depression, presumably due to abnormalities in the dopamine (DA) system. Here, the investigators will test whether expectation-induced mood enhancement is mediated by endogenous DA activity and reward learning, and moderated by individual differences in depression-related personality traits. Healthy participants (N=296) will be tested for potentially relevant personality traits and given an inactive substance (placebo) or a DA D2-receptor antagonist sulpiride (400 mg) in combination with a low vs. high expectation manipulation (fully crossed 2x2 placebo design) before performing a probabilistic reinforcement learning task, an effort expenditure task, and undergo a depressed mood induction procedure. Further, EEG indices will be assessed throughout the tasks. The investigators expect that positive expectation improves participants' reinforcement learning, increases participants' willingness to make effort in order to obtain reward, and leads to less depressive symptoms as indicated by mood ratings upon depressive mood induction. If the overall effect of positive expectations is mediated by DA, high-dose sulpiride should block expectation-induced effects, i.e., the anticipated enhanced reinforcement learning and effort expenditure as well as mood improvement in the high vs. low expectation group.

Conditions

Placebo Effect on Mood Improvement

Keywords

placebo effect; treatment expectations; depression; reinforcement learning; mesolimbic dopamine; EEG

Outcome Measures

Primary Outcomes (3)

• The Positive and Negative Affect Schedule (PANAS)

  With regard to depressive mood induction: the mean of participants' five mood ratings during and immediately after the mood induction procedure. Participants' current mood will be rated on a 5-point Likert scale ranging from 1 = very slightly or not at all to 5 = extremely.

  Five time points: approximately 3 hours after treatment (i.e., substance intake), approximately 4 hours after treatment, approximately 4.5 hours after treatment, approximately 4.75 hours after treatment, and approximately 5 hours after treatment.

• The probabilistic reinforcement learning task

  With regard to probabilistic reinforcement learning: participants' reward learning rate parameter αG as estimated in computational modeling.

  This will be the first task participants undergo approximately 3 hours after treatment (i.e., substance intake) followed by the two other tasks.

• The Effort Expenditure for Rewards Task (EEfRT)

  With regard to effort expenditure: The number of participants' choices for the hard task which required more effort.

  This will be the second task participants undergo which follows the probabilistic reinforcement learning task (approximately 4 hours after treatment) followed by the mood induction procedure.

Secondary Outcomes (3)

• Mood ratings

  Simultaneously as PANAS (see primary outcome 1).

• EEG responses to mood induction

  Approximately 4. 5 hours after treatment (i.e., during the mood induction procedure which follows the probabilistic reinforcement learning task and the EEfRT tasks).

• EEG responses to reward feedback

  Approximately 3 hours after treatment (i.e., simultaneously during the probabilistic reinforcement learning task).

Other Outcomes (15)

• State-Trait-Anxiety-Depression Inventory (STADI)

  For trait aspects: one week to two days prior to the experiment; for state aspects: approximately 30 minutes before treatment.

• Behaviroal Approach System Sensitivity (BIS BAS)

  One week to two days prior to the experiment session.

• Perceived Stress Scale (PSS-10)

  One week to two days prior to the experiment session.

Study Arms (4)

High expectation with sulpiride group

EXPERIMENTAL

Prior to the experimental procedure, participants are told by the study clinicians that an antidepressant sulpiride capsule is administrated, while participants actually receive a sulpiride 400mg-capsule (note that the dose is presumably too high to produce antidepressant effects).

Drug: Sulpiride 400 MG; Behavioral: High expectation manipulation

High expectation with placebo group

EXPERIMENTAL

Prior to the experimental procedure, participants are told by the study clinicians that an antidepressant sulpiride capsule is administrated, while participants actually receive a placebo capsule.

Drug: Placebo; Behavioral: High expectation manipulation

Low expectation with sulpiride group

EXPERIMENTAL

Prior to the experimental procedure, participants are told by the study clinicians that an inactive placebo capsule is administrated, while participants actually receive a sulpiride capsule (400 mg).

Drug: Sulpiride 400 MG; Behavioral: Low expectation manipulation

Low expectation with placebo group

EXPERIMENTAL

Prior to the experimental procedure, participants are told by the study clinicians that an inactive placebo capsule is administrated, and participants actually receive a placebo capsule.

Drug: Placebo; Behavioral: Low expectation manipulation

Interventions

Sulpiride 400 MG DRUG

The substituted benzamide sulpiride is a selective D2-receptor antagonist that is generally well tolerated and has a low affinity to histaminergic, cholinergic, serotonergic, adrenergic, or GABA receptors. Sulpiride is slowly absorbed from the gastrointestinal tract and peak serum levels occur at 3 hours . In low doses (50-200 mg), sulpiride presumably blocks presynaptic autoreceptors, thereby elevating DA levels and reducing depressive symptoms, whereas higher doses lead to a predominant blockade of postsynaptic receptors. The dose in the present study (400 mg) is sufficient for behaviorally relevant modulations of dopaminergic processing with minimal risk of side effects. Note that participants in the sulpiride group actually receive a dose that is presumably too high to produce antidepressant effects.

High expectation with sulpiride group; Low expectation with sulpiride group

Placebo DRUG

Participants receive an inactive placebo capsule.

High expectation with placebo group; Low expectation with placebo group

High expectation manipulation BEHAVIORAL

Participants will be told by the study clinicians that an antidepressive sulpiride capsule is administrated.

High expectation with placebo group; High expectation with sulpiride group

Low expectation manipulation BEHAVIORAL

Participants will be told by the study clinicians that an inactive placebo capsule is administrated.

Low expectation with placebo group; Low expectation with sulpiride group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Right-handed
• Aged 18-60 years
• German native speaker
• Informed consent
• Normal or corrected sight

You may not qualify if:

• Current pregnancy
• Current or history of general medical, neurological or psychological disorders, which preclude sulpiride intake
• Self-reported presence of mental disorders
• Liver, kidney, and bowel disorders
• Regular smoking
• Reported alcohol abuse
• Illegal drug intake
• Regular drug intake by prescription in the past three months
• Dreadlocks
• BMI \< 19 or \> 30
• Unremovable metal objects around the head
• Previous knowledge of Japanese characters
• Excessive caffeine intake (\> 8 cups per day)

Sponsors & Collaborators

• Philipps University Marburg: lead

Study Sites (1)

Department of Psychology, Differential Psychology and Personality Research, Philipps-University of Marburg

Marburg, Hesse, 35032, Germany

Location

MeSH Terms

Conditions

Depression

Interventions

Sulpiride

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Erik M Mueller, Prof. Dr.

  Philipps University Marburg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants will be blinded to the actual substance groups. In order to carry out the expectation manipulation, the clinician scientists will provide participants with substance information that is unrelated to the actual substance that is received by the participants. Hence the clinician scientists are blind to the actual substance (double blind design). Other than providing (invalid) substance information (i.e. the expectation manipulation) and drawing blood samples, the study clinicians do not take part in the remaining experimental procedure. The investigators who accompany participants throughout the experimental procedure are not aware of participants' true substance and expectation allocation.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Personality Psychology

Model Details: A fully crossed 2x2 placebo design will be employed by giving participants either a placebo or a sulpiride capsule in combination with a low vs. high expectation manipulation.

Study Record Dates

• First Submitted: December 21, 2021
• First Posted: January 26, 2022
• Study Start: December 9, 2021
• Primary Completion: September 22, 2023
• Study Completion: September 22, 2023
• Last Updated: January 16, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: With publication

Locations

DE (1)