Biomarkers Associated with Depression Improvement in Veterans with Gulf War Illness Using the Low-Glutamate Diet

Gulf War Illness (GWI) is a chronic multi-symptom neurological disorder affecting veterans of the Gulf War that is commonly comorbid with depression. A secondary data analysis was conducted to examine serum homocysteine and inflammatory cytokines (IFN-γ, IL-6, IL-1β, TNF-α) as potential biomarkers of depression improvement among veterans with GWI after a one-month dietary intervention aimed at reducing excitotoxicity and increasing micronutrients. Analyses, including multiple linear and logistic regression, were conducted in R studio. Dietary adherence was estimated using a specialized excitotoxin food frequency questionnaire (FFQ), and depression was measured using the Center for Epidemiologic Studies Depression (CES-D) scale. After one month on the diet, 52% of participants reported a significant decrease in depression (p < 0.01). Greater dietary adherence (FFQ) was associated with increased likelihood of depression improvement; OR (95% CI) = 1.06 (1.01, 1.11), (p = 0.02). Reduced homocysteine was associated with depression improvement after adjusting for FFQ change (β = 2.58, p = 0.04), and serum folate and vitamin B12 were not mediators of this association. Reduction in IFN-γ was marginally associated with likelihood of depression improvement (OR (95% CI) = 1.11 (0.00, 1.42), (p = 0.06)), after adjustment for potential confounders. Findings suggest that homocysteine, and possibly IFN-γ, may serve as biomarkers for depression improvement in GWI. Larger trials are needed to replicate this work.