A Neurobiological Model of Anhedonia

October 14, 2024 updated by: Dahlia Mukherjee, Milton S. Hershey Medical Center

Inflammatory, Behavioral and Neural Markers of Anhedonia in Major Depressive Disorder

The purpose of this research study is to better understand anhedonia in Major Depressive Disorder by investigating the reward-related neural and inflammatory correlates.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

Background: Despite extensive research on the treatment of Major Depressive Disorder (MDD) relapse rates are as high as 80%. Of those, 30-40% fall into the severe spectrum called treatment resistant depression (TRD) as they fail to respond to at least two lines of antidepressant treatment interventions. TRD has been linked with anhedonia, the inability to experience pleasure or interest in usually enjoyable activities. The neurobiology of anhedonia is poorly understood with recent literature examining an inflammatory association and linking it to deficits in reward-related brain circuitry. The present study examines neurobiological correlates of anhedonia in MDD and TRD, specifically C-Reactive Protein (CRP), IL-6 and ventral striatal (VS) activity. The study also explores whether VS activity mediates the association between inflammation and anhedonia.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Penn State Milton S. Hershey Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Participants will be recruited from the surrounding community as well as through clinics associated with a central Pennsylvania medical center.

Description

Inclusion Criteria:

  • Current diagnosis of MDD based on the MINI International Neuropsychiatric Interview (MINI)
  • For treatment resistant depression participants: unsuccessful treatment with at least 2 types or doses of antidepressant medication treatment
  • Right-handed
  • Capacity for informed consent
  • Score a 9 or higher on the MADRS

Exclusion Criteria:

  • Comorbid Bipolar Disorder
  • Substance use disorder in the last 12 months
  • Schizophrenia, and other psychotic disorders
  • Comorbid illness such as endocrinological illness (e.g. Cushing's disease) rheumatologic illness (e.g., systemic Lupus erythematosus, current treatment with glucocorticoids), and autoimmune diseases (e.g. psoriasis)
  • Pregnancy
  • Daily NSAID or aspirin use and any metallic implant
  • Visual/Hearing Impairments that would keep participant from being able to complete tasks

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Participants with Major Depressive Disorder including TRD
Treatment resistant depression (TRD) participants are defined as participants with Major Depressive Disorder (MDD) who fail to respond to at least two lines of antidepressant medication treatment interventions.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Basal inflammatory marker assessment
Time Frame: 1 hour
Quantify the profile of basal inflammatory markers (IL-6 and C-reactive protein) in blood. Blood will be collected within an hour after consent and will be processed by 3 hours.
1 hour
Behavior during reward-based task - Monetary Incentive Delay Task
Time Frame: 30 minutes
Participants will complete the Monetary Incentive Delay (MID) task, a reward-based task, while undergoing functional magnetic resonance imaging (fMRI). Results will include button press reaction time for the MID task.
30 minutes
Behavior during reward-based task - Reward Probabilistic Reversal Learning Task
Time Frame: 30 minutes
Participants will complete a Reward Probabilistic Reversal Learning Task, a reward-based task, while undergoing functional magnetic resonance imaging (fMRI). Results will include choice behavior, either choice A or choice B, (button press) for this task.
30 minutes
Blood oxygen level dependent (BOLD) activation during reward-based tasks
Time Frame: 1 hour
Participants will undergo functional magnetic resonance imaging (fMRI) while completing the tasks in Outcome 2. Ventral striatum activation during the tasks will be measured by % BOLD signal change. The expected signal change is between .1-.8%.
1 hour

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Mediation model between inflammation and anhedonia
Time Frame: 3 hours
Hierarchical linear mediation analysis will be used to determine if BOLD signal in the ventral striatum during reward based tasks significantly mediates the link between inflammation and anhedonia.
3 hours
Exploratory inflammatory marker assessment
Time Frame: 3 hours

Exploratory analysis of pro (IL-8, TNF-alpha) and anti- inflammatory marker (IL-10) from blood samples will be conducted. All cytokines will be transformed log(x+1) to correct a positive skew and to maintain a meaningful zero. Outlier cytokine values (>3 standard deviations above the mean) and winsorize will be identified by replacing any value with a z-score of greater than 3 SD with the value of 3 SD from the mean. This will be done for each individual cytokine. Z-scores for each individual's cytokine concentration will be calculated based on the means and standard deviations for each cytokine after winsorizing. The composite cytokine score will then be determined by calculating the mean of the basal cytokine Z-scores for each individual.

A composite measure of inflammation may be statistically examined, which would involve combining these cytokines into 1-2 factors.
3 hours
Exploratory analysis of reward related regions
Time Frame: 3 hours
Exploratory analysis of reward related brain regions (ventromedial prefrontal cortex and orbitofrontal cortex) will be conducted using % BOLD signal change. The expected signal change is between .1-.8%.
3 hours

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Punishment-Based Probabilistic Reversal Learning Task Performance
Time Frame: 30 minutes
Participants will complete the Punishment Probabilistic Reversal Learning Task. This task is used to measure punishment-based decision making. Participants will complete 20 practice trials before moving on to 90 actual trials. The 90 trials are divided into three blocks of 30 trials each. At the end of a block of 30 trials, a reversal takes place, i.e. the image which had the higher probability of not losing money now has the lower probability of not losing money and vice versa. Each punishment has a monetary value of $0.10. The participants will start off with $10 and will try to keep as much of that as possible. At the end of the task the screen displays $10 minus the amount of money that the participant lost. Total money lost, total number of win-stay choices and lose-shift choices will be assessed.
30 minutes
Delay Discounting Task Performance
Time Frame: 30 minutes
This task is used to measure the extent to which a participant discounts delayed rewards. The task consists of 51 choices. Each choice is between a smaller monetary reward available immediately and a larger monetary reward received after a delay. For example, "Would you prefer $10 now or $15 in 7 days?" Performance is calculated in percentage of now options chosen. This task measures impulsivity through calculation of the number of "now" options vs the number of "later" options.
30 minutes
Stroop Task
Time Frame: 15 minutes
The Stroop Task is a well validated neuropsychological assessment that measures cognitive functioning. The task measures reaction time and accuracy, therefore a lower time score demonstrates better cognitive functioning than a higher time score.
15 minutes
Go/No-Go Task
Time Frame: 5 minutes
For this task, participants are going to be asked to press the space bar when a green oval appears saying "GO", and to not press the space bar (no response) when a red oval appears saying "NOGO". This is a test of inhibitory control assessed by reaction time and correct/incorrect responses. A lower reaction time and higher number of correct responses is favorable.
5 minutes
Wisconsin Card Sorting Task
Time Frame: 20 minutes
In this task, the participant will need to match a card to one of the four cards that are presented on the top of the screen. The participant will need to click on one of the four cards that match the card on the left. after each trial, the participant will receive feedback. If incorrect, the participant will need to try a different rule to match the cards. The participant can match the cards according to color, number, or shape. The rule the participant is attempting to figure out changes after 10 trials. this task measures shifting and cognitive flexibility by assessing the frequency of errors (total, preservation and non-preservation), and reaction time. A lower total number of errors and lower reaction time is favorable.
20 minutes
N-Back Task
Time Frame: 20 minutes
In this task, participants are presented with a sequence of stimuli one by one. For each stimulus, they need to decide if the current stimulus is the same as the one presented "N" trials ago. The "N" can be 1 trial, 2 trials, 3 trials, etc The higher the number, the more difficult the task. The factors that seem to influence the performance are not only the "N" but also the speed of presentation and the size of the set of stimuli. This is a test of working memory and working memory capacity, which are assessed by response accuracy and response time. A lower response time with higher accuracy is more favorable.
20 minutes
Lexical Decision Task
Time Frame: 5 minutes
In this task, participants will be shown two words on the screen at a time. If both words are correct English words, the participant will press the "A" key. If one or both of the words are non-sense words (for example "FLUMMOL"), the participant will press the button "L". The participant will need to respond within 2 seconds for the answer to be recorded. This is a test of semantic memory and the word retrieval assessed through reaction time and accuracy. A lower reaction time and greater accuracy is more favorable.
5 minutes

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Milton S. Hershey Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institutes of Health (NIH)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Dahlia Mukherjee, Ph.D, Milton S. Hershey Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 19, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 30, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 30, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 31, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 17, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 29, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 16, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 14, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • STUDY00011450
  • UL1TR002014 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Depression

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings