DepressionNCT06080646
Reward Processing and Depressive Subtypes: Identifying Neural Biotypes
An observational study of Depression and Depressive Disorder, run by San Francisco Veterans Affairs Medical Center at 1 site in United States.
Trial summary
Deficits in motivation and pleasure are common in depression, and thought to be caused by alterations in the ways in which the brain anticipates, evaluates, and adaptively uses reward-related information. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Depression, Depressive Disorder, Major Depressive Disorder
- How many people
- 158 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2021to 1 Sep 2025
- 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 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Individuals with Major Depressive Disorder (age range 18 - 70)
Who may be able to join
- 18-70 years with a diagnosis of major depressive disorder (MDD) for MDD group, or without for unaffected comparison (UC) group
- Negative metal screen for MRI safety
- Normal (or corrected to normal) vision
Who cannot join
- Past or present neurological problems (including seizures and head trauma resulting in neurological or cognitive symptoms)
- Loss of consciousness (LOC) greater than 30 minutes or any LOC with neurologic symptoms
- Major medical conditions (e.g., seizure disorders, treatment with anticonvulsant medication, endocrine disorders, significant cardiac pathology)
- Substance dependence, within the past year, or failed urine toxicology on the day of neuroimaging sessions
- Known claustrophobia
- Current Pregnancy
- IQ estimate < 70
Trial locations and contacts
1 site in 1 country.
United States1 site
San Francisco Healthcare System
San Francisco, California, 94121
About this study
Official title: Reward Processing and Depressive Subtypes: Identifying Neural Biotypes Related to Suicide Risk, Resilience, and Treatment Response
Deficits in motivation and pleasure are common in depression, and thought to be caused by alterations in the ways in which the brain anticipates, evaluates, and adaptively uses reward-related information. However, reward processing is a complex, multi-circuit phenomenon, and the precise neural mechanisms that contribute to the absence or reduction of pleasure and motivation are not well understood. Variation in the clinical presentation of depression has long been a rule rather than an exception, including individual variation in symptoms, severity, and treatment response. This heterogeneity complicates understanding of depression and thwarts progress toward disease classification and treatment planning. Discovery of depression-specific biomarkers that account for neurobiological variation that presumably underlies distinct clinical manifestations is critical to this larger effort.
Read the detailed description
This study combines clinically motivated questions with in-depth study of neurobiological mechanisms to evaluate how reward system neurobiology contributes to expression of reward-related deficits, such as decreased pleasure and motivation in major depressive disorder (MDD). Conceptually, the investigator will use a multi-measure approach, by studying basic brain responses to reward anticipation as well as higher-order aspects of reward processing necessary for decision-making.
Methodologically, the investigator will combine fMRI, EEG, and behavioral assessment, to more fully characterize reward-related brain functions and their clinical correlates. In addition to evaluating reward effects between MDD and healthy controls (HC), the investigator will also focus on understanding the relationship between reward processing and clinical features of high relevance to depression, with an emphasis on suicidality.
- Conditions
- Depression, Depressive Disorder, Major Depressive Disorder, Major Depressive Episode, Depressive Symptoms, Anhedonia
- Being tested
- cross-sectional MRI and EEG assessments (NO INTERVENTION)
- Keywords
- reward, motivation, EEG, fMRI, MRI, functional MRI, amotivation, avolition, suicidality, suicide
- Medical subject headings
- Depression, Depressive Disorder, Depressive Disorder, Major, Anhedonia, Suicidal Ideation, Suicide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cross-sectional MRI and EEG assessments (NO INTERVENTION)Other
Also called cross-sectional MRI and EEG assessments
n/a there is no intervention in this observational study
| Study group | Role | What they receive |
|---|---|---|
| MDD (Major Depressive Disorder) Group | Individuals (ages 18-70 years) who meet DSM-5 criteria for MDD, as assessed using the Structured Clinical Interview for DSM-5 (SCID-5), with Stable psychiatric medication regime for > 1 month will be recruited for participation in EEG and fMRI sessions in this observational study. Receives: Other: cross-sectional MRI and EEG assessments (NO INTERVENTION) | |
| Unaffected Comparison Group | 50 unaffected comparison participants will be matched as a group to the age, race, educational level, handedness, and parental socio-economic status of the MDD patient group will be recruited for participation in EEG and fMRI testing sessions identical to those administered to the patients Receives: Other: cross-sectional MRI and EEG assessments (NO INTERVENTION) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Stimulus preceding negativity
Stimulus preceding negativity (EEG measure of reward anticipation) of reward-related brain activation patterns and EEG responses on participants
Measured: 1 month (EEG measure of reward anticipation)
Reward positivity
Reward positivity (EEG measure of reward feedback) of reward-related brain activation patterns and EEG responses on participants
Measured: 1 month (EEG measure of reward feedback)
Late positive potential
Late positive potential (EEG measure of affective salience) of reward-related brain activation patterns and EEG responses on participants
Measured: 1 month (EEG measure of effective salience)
fMRI response to win vs. loss reward feedback
fMRI response to win vs. loss reward feedback of reward-related brain activation patterns and EEG responses on participants
Measured: 1 month (fMRI data)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2023
- Study start1 Jun 2021
- Primary completion30 Jun 2025
- Study completion1 Sep 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DepressionStudies of the same condition, open and under way.
- 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
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 158 participants (actual)
Sponsor and investigators
- Lead sponsor
- San Francisco Veterans Affairs Medical Center
- Sponsor type
- US federal agency
- Responsible party
- Principal investigator, Susanna Fryer, PhD, San Francisco Veterans Affairs Medical Center
- Investigators
- Susanna L Fryer, PhD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06080646
- Sponsor's protocol ID
- CX001980
- Status last verified
- Sep 2026
- First submitted
- 28 Sep 2023
- Last updated
- 8 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Not part of currently approved protocol or original agreement with sponsor
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reward Processing and Depressive Subtypes: Identifying Neural Biotypes Related to Suicide Risk, Resilience, and Treatment Response
- ClinicalTrials.gov ID
- NCT06080646
- Acronym / sponsor ID
- CX001980
- Conditions
- Depression, Depressive Disorder, Major Depressive Disorder, Major Depressive Episode, Depressive Symptoms, Anhedonia
- Keywords
- reward, motivation, EEG, fMRI, MRI, functional MRI, amotivation, avolition
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 158 participants (actual)
- Lead sponsor
- San Francisco Veterans Affairs Medical CenterUS federal agency
- Study start
- 1 Jun 2021 (actual)
- Primary completion
- 30 Jun 2025 (actual)
- Study completion
- 1 Sep 2025 (actual)
- First posted
- 12 Oct 2023 (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.
Deficits in motivation and pleasure are common in depression, and thought to be caused by alterations in the ways in which the brain anticipates, evaluates, and adaptively uses reward-related information. However, reward processing is a complex, multi-circuit phenomenon, and the precise neural mechanisms that contribute to the absence or reduction of pleasure and motivation are not well understood. Variation in the clinical presentation of depression has long been a rule rather than an exception, including individual variation in symptoms, severity, and treatment response. This heterogeneity complicates understanding of depression and thwarts progress toward disease classification and treatment planning. Discovery of depression-specific biomarkers that account for neurobiological variation that presumably underlies distinct clinical manifestations is critical to this larger effort.
Detailed description
This study combines clinically motivated questions with in-depth study of neurobiological mechanisms to evaluate how reward system neurobiology contributes to expression of reward-related deficits, such as decreased pleasure and motivation in major depressive disorder (MDD). Conceptually, the investigator will use a multi-measure approach, by studying basic brain responses to reward anticipation as well as higher-order aspects of reward processing necessary for decision-making.
Methodologically, the investigator will combine fMRI, EEG, and behavioral assessment, to more fully characterize reward-related brain functions and their clinical correlates. In addition to evaluating reward effects between MDD and healthy controls (HC), the investigator will also focus on understanding the relationship between reward processing and clinical features of high relevance to depression, with an emphasis on suicidality.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MDD (Major Depressive Disorder) Group | – | Other: cross-sectional MRI and EEG assessments (NO INTERVENTION)Individuals (ages 18-70 years) who meet DSM-5 criteria for MDD, as assessed using the Structured Clinical Interview for DSM-5 (SCID-5), with Stable psychiatric medication regime for > 1 month will be recruited for participation in EEG and fMRI sessions in this observational study. |
| Unaffected Comparison Group | – | Other: cross-sectional MRI and EEG assessments (NO INTERVENTION)50 unaffected comparison participants will be matched as a group to the age, race, educational level, handedness, and parental socio-economic status of the MDD patient group will be recruited for participation in EEG and fMRI testing sessions identical to those administered to the patients |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Individuals with Major Depressive Disorder (age range 18 - 70)
Key inclusion criteria (3 listed)
- 18-70 years with a diagnosis of major depressive disorder (MDD) for MDD group, or without for unaffected comparison (UC) group
- Negative metal screen for MRI safety
- Normal (or corrected to normal) vision
Key exclusion criteria (7 listed)
- Past or present neurological problems (including seizures and head trauma resulting in neurological or cognitive symptoms)
- Loss of consciousness (LOC) greater than 30 minutes or any LOC with neurologic symptoms
- Major medical conditions (e.g., seizure disorders, treatment with anticonvulsant medication, endocrine disorders, significant cardiac pathology)
- Substance dependence, within the past year, or failed urine toxicology on the day of neuroimaging sessions
- Known claustrophobia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| cross-sectional MRI and EEG assessments (NO INTERVENTION)Also: cross-sectional MRI and EEG assessmentsn/a there is no intervention in this observational study | Other | MDD (Major Depressive Disorder) Group, Unaffected Comparison Group |
Primary outcome
Stimulus preceding negativity
Time frame: 1 month (EEG measure of reward anticipation)
Stimulus preceding negativity (EEG measure of reward anticipation) of reward-related brain activation patterns and EEG responses on participants
Reward positivity
Time frame: 1 month (EEG measure of reward feedback)
Reward positivity (EEG measure of reward feedback) of reward-related brain activation patterns and EEG responses on participants
Late positive potential
Time frame: 1 month (EEG measure of effective salience)
Late positive potential (EEG measure of affective salience) of reward-related brain activation patterns and EEG responses on participants
fMRI response to win vs. loss reward feedback
Time frame: 1 month (fMRI data)
fMRI response to win vs. loss reward feedback of reward-related brain activation patterns and EEG responses on participants
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 8 Sep 2026.
- Individual participant dataSharing planned: No. Not part of currently approved protocol or original agreement with sponsor
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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.
Susanna L Fryer, PhD principal investigator
University of California, San Francisco
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 Depression and Depressive Disorder, run by San Francisco Veterans Affairs 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 3 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 8 Sep 2026. 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?
Stimulus preceding negativity (time frame: 1 month (EEG measure of reward anticipation)). 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 8 Sep 2026.