Leucine as a Probe of Kynurenine-Induced Glutamate and Neural Circuit Dysfunction in Midlife Depression
Emory University
Summary
The study aims to investigate the effects of a 6-week leucine challenge on brain chemistry, connectivity, and behavior in people with midlife depression. The researchers will compare the leucine and an active comparator arm (lysine) for 6 weeks.
Description
Major depression is a common and serious mental health condition that can severely impact a person's quality of life. Some symptoms, like loss of pleasure in activities and slowed movements, may be signs that the depression will be harder to treat. These symptoms are also linked to a higher risk of dementia later in life. Scientists think that long-term, low-level inflammation in the body may contribute to depression, especially in middle-aged adults. This inflammation may affect areas of the brain involved in feeling good and controlling movement. One way inflammation might lead to depressi…
Eligibility
- Age range
- 35–65 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Able and willing to provide informed consent * Diagnosis of major depression per Structured Interview for DSM-V (SCID-V) * Moderate to severe depression- Inventory of Depressive Symptoms - Self Reported (IDS-SR score \>34). * SHAPS score \>30 on the 0-56 scale * Body mass index (BMI) between 20-35 kg/m2 * Plasma CRP \>1 mg/L * No contraindications to MRI * Availability of friends or family for transportation after lumbar puncture procedure * Clinically significant findings on EKG * Patient Health Questionnaire (PHQ-9) score greater than 10 * Willingness to adopt contrace…
Interventions
- DrugL-leucine
L-leucine is an essential amino acid used to competitively inhibit kynurenine uptake into the brain via the large neutral amino acid transporter (LAT1). The proposed dose for L-leucine is 4.31 g/day, administered orally.
- DrugL-lysine
L-lysine monohydrochloride is also an essential amino acid. It serves as an active comparator to control for general effects on brain protein synthesis and enters the brain through separate cationic amino acid transporters. The proposed dose for L-lysine is 6 g/day, administered orally
Location
- Emory University HospitalAtlanta, Georgia