Clinical trial NCT06080646: Reward Processing and Depressive Subtypes: Identifying Neural Biotypes
Official title: Reward Processing and Depressive Subtypes: Identifying Neural Biotypes Related to Suicide Risk, Resilience, and Treatment Response
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Depression
Depressive Disorder
Major Depressive Disorder
Major Depressive Episode
Depressive Symptoms
Anhedonia
Keywords: reward
motivation
EEG
fMRI
MRI
functional MRI
amotivation
avolition
suicidality
suicide
Lead sponsor: San Francisco Veterans Affairs Medical Center
Sponsor class: FED
First posted: 2023-10-12
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Individuals with Major Depressive Disorder (age range 18 - 70)

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.

Eligibility 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

Primary outcomes:
measure: Stimulus preceding negativity
timeFrame: 1 month (EEG measure of reward anticipation)
measure: Reward positivity
timeFrame: 1 month (EEG measure of reward feedback)
measure: Late positive potential
timeFrame: 1 month (EEG measure of effective salience)
measure: fMRI response to win vs. loss reward feedback
timeFrame: 1 month (fMRI data)
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: San Francisco Healthcare System
state: California
Study officials:
affiliation: University of California, San Francisco
name: Susanna L Fryer, PhD
role: PRINCIPAL_INVESTIGATOR
References: