(OR04-04-23) Biomarkers of Depression Improvement Using the Low Glutamate Diet in Gulf War Illness

Objectives: Glutamatergic dysregulation and excitotoxicity are known contributors to the pathophysiology of depression. This study examined serum biomarker changes associated with depression improvement in veterans with Gulf War Illness (GWI) after one month on the low glutamate diet from a previous randomized, controlled study.

Methods: Depression was measured using the Center for Epidemiologic Studies Depression Scale (CES-D), while dietary adherence used an excitotoxin food frequency questionnaire (FFQ) pre- and post-diet. The biomarkers of interest included homocysteine and inflammatory cytokines IFN-γ, IL-6, IL-1β , and TNF-α. Using R Studio, homocysteine and cytokine changes were examined for associations with depression change after one month using independent t-tests and multivariable linear regression. Logistic regression was used to estimate the likelihood of depression improvement (Y/N) defined as >30% lower CES-D or a score < 16 for each biomarker, adjusting for potential confounding factors.

Results: After 30-days on the diet, 52% of the veterans reported significant depression improvement (p < 0.01), and this was associated with dietary adherence (p < 0.01). Higher consumption of dietary excitotoxins was associated with a significantly reduced likelihood of depression improvement; OR (95% CI) = 0.95 (0.90, 0.99), (p=0.02). Decreased homocysteine was linearly associated with reduced depression scores, after adjustment for change in FFQ (ß = 2.58, p = 0.04). Change in the inflammatory cytokines was not associated with depression change, except for a marginal association with IFN-γ (p=0.08). Higher IFN-γ levels were marginally associated with a lower likelihood of depression improvement (OR (95% CI) = 0.90 (0.80, 1.00), (p=0.06).), after adjusting for age, sex, race, BMI change, and FFQ change.

Conclusions: These data suggest that homocysteine, and perhaps IFN-γ, may serve as biomarkers that predict depression improvement on the low glutamate diet in those with GWI. Larger clinical trials are needed.

Funding Sources: This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the GWI Research Program under Award No. W81XWH-17-1-0457. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the Department of Defense.