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CompletedNCT06080646Updated Sep 8, 2026

Reward Processing and Depressive Subtypes: Identifying Neural Biotypes

An observational study in Depression, Depressive Disorder and Major Depressive Disorder, sponsored by San Francisco Veterans Affairs Medical Center. Completed at 1 site in United States. Open to participants aged 18 Years to 70 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-09-08.

Sponsored by San Francisco Veterans Affairs Medical Center · Observational

Study type
Observational
Model
Case-control
Time perspective
Cross-sectional
Enrollment
158
Ages
18 Years to 70 Years
Sex
All
01

Study 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. 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.

02

Conditions studied

  • Depression
  • Depressive Disorder
  • Major Depressive Disorder
  • Major Depressive Episode
  • Depressive Symptoms
  • Anhedonia

Keywords

  • reward
  • motivation
  • EEG
  • fMRI
  • MRI
  • functional MRI
  • amotivation
  • avolition
  • suicidality
  • suicide
03

Who can participate

Ages eligible
18 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
Yes
Sampling method
Non-probability sample

Study population

Individuals with Major Depressive Disorder (age range 18 - 70)

  • Our studies require some in-person visits to our research lab, located at 42nd Ave and Clement St in San Francisco.
  • Because this study includes an MRI, part of the screening process will be to ensure you don't have any metal in your body, you do not have head or neck tattoos, and you are comfortable inside the MRI scanner.

Inclusion criteria

Inclusion Criteria:

  • 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

Exclusion criteria

Exclusion Criteria:

  • 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
04

Study design

Observational model
Case-control
Time perspective
Cross-sectional
Enrollment
158 participants (actual)
Patient registry
No

Groups and cohorts

  • 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.

    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

    Other: cross-sectional MRI and EEG assessments (NO INTERVENTION)

Interventions

  • Othercross-sectional MRI and EEG assessments (NO INTERVENTION)

    n/a there is no intervention in this observational study

    Also known as: cross-sectional MRI and EEG assessments

05

What researchers measure

Primary outcomes

  1. Stimulus preceding negativity

    Stimulus preceding negativity (EEG measure of reward anticipation) of reward-related brain activation patterns and EEG responses on participants

    Time frame: 1 month (EEG measure of reward anticipation)

  2. Reward positivity

    Reward positivity (EEG measure of reward feedback) of reward-related brain activation patterns and EEG responses on participants

    Time frame: 1 month (EEG measure of reward feedback)

  3. Late positive potential

    Late positive potential (EEG measure of affective salience) of reward-related brain activation patterns and EEG responses on participants

    Time frame: 1 month (EEG measure of effective salience)

  4. 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

    Time frame: 1 month (fMRI data)

06

Study locations

1 site
  • San Francisco Healthcare System
    San Francisco, California 94121, United States
07

References and documents

Individual participant data

Plan to share: No — Not part of currently approved protocol or original agreement with sponsor

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT06080646
Lead sponsor
San Francisco Veterans Affairs Medical Center
Responsible party
Susanna Fryer, PhD (Staff Psychologist/Clinician Investigator, San Francisco Veterans Affairs Medical Center) — Principal investigator
First posted
Oct 12, 2023
Start date
Jun 1, 2021
Primary completion
Jun 30, 2025
Completion
Sep 1, 2025
Last update
Sep 8, 2026

Study contacts

Susanna L Fryer, PhD
principal investigator · University of California, San Francisco

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.

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