Leucine in Midlife Depression

Prior treatment

• Concomitant medications:
  • Immune-active medications (e.g., non-steroidal anti-inflammatory agents).
  • Antibiotics and immunizations in the past 2 weeks.
  • Topical or inhaled steroids within the past week.
  • Oral/parenteral steroids in the last 6 months.
  • Supplements that impact the immune system (e.g., omega-3, probiotics) within the past 2 weeks.
  • Psychotropic medications within the last 4 weeks (8 weeks for fluoxetine).
  • Daily use of sedative-hypnotics, benzodiazepines, and opiates.
• Concomitant Treatment for Depression:
  • \-- Treatments with antidepressant medications or those with antidepressant effects (dopamine supplements).
• Treatment for General Medical Conditions (GMCs):
  • Stabilized medications are allowed if maintained at the same dose during the trial.
  • Multiple recent changes in concomitant medications reviewed by the study PI

Other illness

• Leucine-Specific:
  • History of maple syrup urine disease
  • Risk of hypoglycemia (unstable diabetes)
  • History of vitamin B6 deficiency, relative
• Cognitive:
  • --Cognitive impairment (MMSE score \<28)
• Psychiatric Disorders:
  • Lifetime diagnosis of psychotic disorders.
  • Current mania/hypomania.
  • Substance use disorder in the last 6 months.
  • Active suicidal ideation:
  • Psychiatric hospitalization in the past year.
  • Suicide attempts within the last five years.
  • Scores \>3 on the Columbia Suicide Severity Rating Scale (C-SSRS)
  • Binge eating in the absence of mood symptoms increases.
  • Primary diagnosis of severe DSM-V79 anxiety disorders.
  • Primary diagnosis of DSM-V PTSD (if severity exceeds major depression).
  • Primary diagnosis of DSM-V obsessive-compulsive disorders.
  • Significant personality disorders with multiple hospitalizations or suicide attempts.
  • Developmental disorders (e.g., ADHD).
• Medical Disorders:
  • Unstable medical disorders (frequent provider or medication changes).
  • Lifetime diagnosis/treatment of cancers (excluding basal cell carcinoma).
  • Lifetime diagnosis/treatment of autoimmune disorders.
  • Lifetime exposure to chemotherapeutic agents.

Lab values

• Lysine-Specific:
  • On calcium supplements, relative
  • History of renal/gall stones (could cleared by a primary care provider)

Other

• MRI Considerations:
  • \-- Location and quantity of metallic objects safe to MR
• Population
  • Pregnant women.
  • Children.
  • Prisoners.
  • Individuals unable to consent

• 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 contraceptive measures. Persons exempt from contraception requirements are:
  • Persons assigned male at birth
  • Persons assigned female at birth who:
  • have undergone a hysterectomy or bilateral oophorectomy; or
  • have been naturally postmenopausal for at least 24 consecutive months (i.e., has NOT had menses at any time in the preceding 24 consecutive months)