Reward Processing and Depressive Subtypes: Identifying Neural Biotypes

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.

Study Overview

• Status: Recruiting
• Conditions: Depressive Disorder; Depression; Anhedonia; Depressive Symptoms; Major Depressive Disorder; Major Depressive Episode
• Intervention / Treatment: Other: cross-sectional MRI and EEG assessments (NO INTERVENTION)

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 Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Jason Hemmerle, MBA; Phone Number: 24711 415 221 4810; Email: jason.hemmerle@ucsf.edu
• Study Contact Backup: Name: Kaitlyn Dal Bon, BA; Phone Number: 23946 415 221 4810; Email: kaitlyn.dalbon@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94121
      • Recruiting
      • San Francisco Healthcare System
      • Contact: Jason Hemmerle, MBA; Phone Number: 24711 415-221-4810; Email: jason.hemmerle@ucsf.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

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

Description

• 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:

• 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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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); n/a there is no intervention in this observational study; Other Names: cross-sectional MRI and EEG assessments
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); n/a there is no intervention in this observational study; Other Names: cross-sectional MRI and EEG assessments

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stimulus preceding negativity	Stimulus preceding negativity (EEG measure of reward anticipation) of reward-related brain activation patterns and EEG responses on participants	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	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	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	1 month (fMRI data)

Collaborators and Investigators

• Sponsor: San Francisco Veterans Affairs Medical Center
• Investigators: Principal Investigator: Susanna L Fryer, PhD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: September 28, 2023
• First Submitted That Met QC Criteria: October 5, 2023
• First Posted (Actual): October 12, 2023

Study Record Updates

• Last Update Posted (Actual): August 2, 2024
• Last Update Submitted That Met QC Criteria: July 31, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: MRI; functional MRI; fMRI; suicide; EEG; reward; motivation; suicidality; amotivation; avolition
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Nervous System Diseases; Mood Disorders; Neurologic Manifestations; Neurobehavioral Manifestations; Depression; Depressive Disorder; Anhedonia; Depressive Disorder, Major
• Other Study ID Numbers: CX001980

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Not part of currently approved protocol or original agreement with sponsor

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No