Reward Processing and Depressive Subtypes: Identifying Neural Biotypes

Study Overview
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Brief Summary
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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
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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.

Official Title
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Reward Processing and Depressive Subtypes: Identifying Neural Biotypes Related to Suicide Risk, Resilience, and Treatment Response

Conditions
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Depression, Depressive Disorder, Major Depressive Disorder, Major Depressive Episode, Depressive Symptoms, Anhedonia

Intervention / Treatment
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* Other: cross-sectional MRI and EEG assessments (NO INTERVENTION)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| MDD (Major Depressive Disorder) Group<br>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)<br>* n/a there is no intervention in this observational study<br>* Other names: cross-sectional MRI and EEG assessments;|
| Unaffected Comparison Group<br>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)<br>* n/a there is no intervention in this observational study<br>* Other names: cross-sectional MRI and EEG assessments;|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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reward, motivation, EEG, fMRI, MRI, functional MRI, amotivation, avolition, suicidality, suicide