AnhedoniaNCT05629520
A Neurobiological Model of Anhedonia
An observational study of Anhedonia and Depression, run by Milton S. Hershey Medical Center at 1 site in United States.
Trial summary
The purpose of this research study is to better understand anhedonia in Major Depressive Disorder by investigating the reward-related neural and inflammatory correlates. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Anhedonia, Depression
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Feb 2020to 30 Jul 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Participants will be recruited from the surrounding community as well as through clinics associated with a central Pennsylvania medical center.
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
About this study
Official title: 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.
Read the 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.
- Conditions
- Anhedonia, Depression
- Keywords
- Depression, Anhedonia, Reward Related Neural Circuitry, Inflammation
- Medical subject headings
- Anhedonia, Depression, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 being measured
The primary outcome is the main question the study is designed to answer.
Basal inflammatory marker assessment
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.
Measured: 1 hour
Behavior during reward-based task - Monetary Incentive Delay Task
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.
Measured: 30 minutes
Behavior during reward-based task - Reward Probabilistic Reversal Learning Task
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.
Measured: 30 minutes
Blood oxygen level dependent (BOLD) activation during reward-based tasks
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%.
Measured: 1 hour
Secondary outcomes (3)
Mediation model between inflammation and anhedonia
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.
Measured: 3 hours
Exploratory inflammatory marker assessment
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.
Measured: 3 hours
Exploratory analysis of reward related regions
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%.
Measured: 3 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2022
- Study start19 Feb 2020
- Primary completion30 Jul 2024
- Study completion30 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AnhedoniaStudies of the same condition, open and under way.
- More trials run by Milton S. Hershey Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Milton S. Hershey Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Responsible party
- Principal investigator, Dahlia Mukherjee, Milton S. Hershey Medical Center
- Investigators
- Dahlia Mukherjee, Ph.D, Principal investigator, Milton S. Hershey Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05629520
- Sponsor's protocol ID
- STUDY00011450
- Other IDs
- UL1TR002014
- Status last verified
- Oct 2024
- First submitted
- 31 Oct 2022
- Last updated
- 16 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inflammatory, Behavioral and Neural Markers of Anhedonia in Major Depressive Disorder
- ClinicalTrials.gov ID
- NCT05629520
- Acronym / sponsor ID
- STUDY00011450
- Conditions
- Anhedonia, Depression
- Keywords
- Depression, Anhedonia, Reward Related Neural Circuitry, Inflammation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Milton S. Hershey Medical CenterUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- 19 Feb 2020 (actual)
- Primary completion
- 30 Jul 2024 (actual)
- Study completion
- 30 Jul 2024 (actual)
- First posted
- 29 Nov 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study is to better understand anhedonia in Major Depressive Disorder by investigating the reward-related neural and inflammatory correlates.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Participants will be recruited from the surrounding community as well as through clinics associated with a central Pennsylvania medical center.
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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.
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.
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.
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%.
3 secondary outcomes
Mediation model between inflammation and anhedonia
Time frame: 3 hours
Exploratory inflammatory marker assessment
Time frame: 3 hours
Exploratory analysis of reward related regions
Time frame: 3 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dahlia Mukherjee, Ph.D principal investigator
Milton S. Hershey Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Anhedonia and Depression, run by Milton S. Hershey Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Basal inflammatory marker assessment (time frame: 1 hour). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2024.