Exploring interleukin-6, lipopolysaccharide binding protein and brain-derived neurotrophic factor following 12 weeks of adjunctive minocycline treatment for depression

Objective: This study aimed to explore effects of adjunctive minocycline treatment on inflammatory and neurogenesis markers in major depressive disorder (MDD). Methods: Serum samples were collected from a randomised, placebo-controlled 12-week clinical trial of minocycline (200mg/day, added to treatment as usual) for adults (n=71) experiencing MDD to determine changes in interleukin-6 (IL-6), lipopolysaccharide binding protein (LBP) and brain derived neurotrophic factor (BDNF). General Estimate Equation modelling explored moderation effects of baseline markers and exploratory analyses investigated associations between markers and clinical outcomes. Results: There was no difference between adjunctive minocycline or placebo groups at baseline or week 12 in the levels of IL-6 (week 12; placebo 2.06±1.35 pg/ml; minocycline 1.77±0.79 pg/ml; p=0.317), LBP (week 12; placebo 3.74±0.95 µg/ml; minocycline 3.93±1.33 µg/ml; p=0.525) or BDNF (week 12; placebo 24.28±6.69 ng/ml; minocycline 26.56±5.45 ng/ml; p=0.161). Higher IL-6 levels at baseline were a predictor of greater clinical improvement. Exploratory analyses suggested that the change in IL-6 levels were significantly associated with anxiety symptoms (HAMA; p=0.021) and quality of life (Q-LES-Q-SF; p=0.023) scale scores. No other clinical outcomes were shown to have this mediation effect, nor did the other markers (LBP or BDNF) moderate clinical outcomes. Conclusion: There were no overall changes in IL-6, LBP or BDNF following adjunctive minocycline treatment. Exploratory analyses suggest a potential role of IL-6 on mediating anxiety symptoms with MDD. Future trials may consider enrichment of recruitment by identifying several markers or a panel of factors to better represent an inflammatory phenotype in MDD with larger sample size.