Reward Processing and Depressive Subtypes: Identifying Neural Biotypes

Recruiting

• Conditions: Depression; Depressive Disorder; Major Depressive Disorder; Major Depressive Episode; Depressive Symptoms; Anhedonia
• Interventions: Other: cross-sectional MRI and EEG assessments (NO INTERVENTION)

• Registration Number: NCT06080646
• Lead Sponsor: San Francisco Veterans Affairs Medical Center

Brief 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.

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 Timeline

• Study Start: 2021-06-01
• Study First Submitted: 2023-09-28
• Study First Submitted QC: 2023-10-05
• Study First Posted: 2023-10-12
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-31
• Last Update Posted: 2024-08-02
• Primary Completion: 2025-06-01
• Study Completion: 2025-09-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 150

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

• 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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
MDD (Major Depressive Disorder) Group	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	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

Primary Outcome Measures

Name	Time	Method
fMRI response to win vs. loss reward feedback	1 month (fMRI data)	fMRI response to win vs. loss reward feedback of reward-related brain activation patterns and EEG responses on participants
Late positive potential	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
Stimulus preceding negativity	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	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

Trial Locations

Locations (1)

San Francisco Healthcare System; 🇺🇸 San Francisco, California, United States