1/2-Dopaminergic Dysfunction in Late-Life Depression (The D3 Study)

• Status: Recruiting
• Trial end date: 2027-08-01
• Target enrollment: 0
• Participant gender: All

Summary

Growing evidence suggests that dopamine contributes to key cognitive, emotional, and motor functions across the lifespan. In Late-Life Depression (LLD), dysfunction in these areas is common, predicts poor outcomes, and manifests as difficulties in motivation and effort along with cognitive and gait impairment. While studies of dopamine function in early and midlife depression primarily focus on individuals' ability to feel pleasure and respond to rewards, they often exclude the cognitive and physical function domains relevant for older adults despite a recognized decline in dopamine function with normal aging. The objectives of this collaborative R01 proposal between Columbia University/New York State Psychiatric Institute and Vanderbilt University Medical Center are to: 1) characterize dopaminergic dysfunction in LLD across cognitive, emotional, and motor domains at several levels of analysis (cellular Positron Emission Tomography [PET], circuit Magnetic Resonance Imaging [MRI], and behavioral / self-report); and 2) examine the responsivity of dopamine-related circuits and behavior to stimulation with carbidopa/levodopa (L-DOPA).

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: New York State Psychiatric Institute
• Collaborators: Columbia University; Emory University; National Institute of Mental Health (NIMH); Vanderbilt University Medical Center
• Treatments: Carbidopa; Carbidopa, levodopa drug combination; Levodopa

Criteria

Inclusion Criteria:

Depressed Subjects:

1. Age 60 years or older (female subjects will be post-menopausal by virtue of their age, but last menstrual period month and year will be documented in the study database)

2. Diagnosis and Statistical Manual (DSM-5) diagnosis of Major Depressive Disorder (MDD) or Persistent Depressive Disorder (PDD)

3. Montgomery Asberg Depression Rating Scale Score (MADRS) >=15

4. Decreased processing speed or decreased gait speed

5. Capable of providing informed consent and complying with study procedures

6. Alternative standard treatments for MDD or PDD have been discussed and the individual agrees to be involved in an experimental treatment

Psychiatrically Healthy Elders:

1. Age 60 years or older years old

2. MADRS < 8

3. Capable of providing informed consent and complying with study procedures

Exclusion Criteria:

Depressed Subjects:

1. Diagnosis of Substance Use Disorder (excluding Tobacco Use Disorder) in the past 12 months

2. History of psychosis (except brief psychosis associated with transient medical conditions [e.g., delirium, urinary tract infection, etc], psychotic disorder, mania, or bipolar disorder.

3. Primary neurological disorder, including dementia, stroke, Parkinson's disease, or epilepsy.

4. Mini Mental State Examination (MMSE) < 24

5. MADRS suicide item >4 or other indication of acute suicidality

6. Current or recent (within the past 2 weeks) treatment with antidepressants, antipsychotics, or mood stabilizers

7. History of hypersensitivity, allergy, or intolerance to L-DOPA

8. Any physical or intellectual disability adversely affecting ability to complete assessments.

9. Acute, severe, or unstable medical illness

10. Mobility limiting osteoarthritis of any lower extremity joints, symptomatic lumbar spine disease, or history of joint replacement or spine surgery that limits mobility

11. Contraindication to MRI scanning (Metal implants, pacemaker, metal prostheses, metal orthodontic appliances in the body unless there is confirmation that the substance is MRI compatible.)

12. History of significant radioactivity exposure (nuclear medicine studies or occupational exposure)

13. Has a medical condition managed with medication and/or device and the managing physician considers the condition and/or its management a contraindication to the research use of L-DOPA in this participant

Psychiatrically Healthy Elders:

1. Any personal history of DSM-5 disorder

2. Family history of MDD in first-degree relative

3. Plus, Exclusion criteria 8-12 above