Reward Processing and Depressive Subtypes: Identifying Neural Biotypes

San Francisco Veterans Affairs Medical Center

Status: Enrolling

Conditions: Depressive Symptoms; Major Depressive Disorder; Major Depressive Episode; Anhedonia; Depression; Depressive Disorder

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

Study type: Observational

Funder types: Other U.S. Federal agency

Identifiers

NCT06080646

CX001980

Details and patient eligibility

About

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.

Full 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.

Enrollment: 150 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

• 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

Trial design

150 participants in 2 patient groups

MDD (Major Depressive Disorder) Group

Description:

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.

Treatment:

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

Unaffected Comparison Group

Description:

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

Treatment:

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