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
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.
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.
Individuals with Major Depressive Disorder (age range 18 - 70)
Inclusion Criteria:
Exclusion Criteria:
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)
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)
n/a there is no intervention in this observational study
Also known as: cross-sectional MRI and EEG assessments
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)
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)
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)
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)
Plan to share: No — Not part of currently approved protocol or original agreement with sponsor
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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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San Francisco Veterans Affairs Medical Center