Objective: This study examined the effect of adjunctive minocycline on psychopathology and possibly relevant biomarkers in patients with schizophrenia. Method: In a 16-week randomized, double-blind, placebo-controlled study, subjects received either minocycline (200 mg per day) or placebo. Psychopathology was assessed using the Scale for the Assessment of Negative Symptoms (SANS) and the Positive and Negative Syndrome Scale (PANSS) at baseline and week 16. Plasma levels of tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta) and nitric oxide metabolites were assessed at both time points. Results: Fifty-five patients completed the study (27 in the minocycline group, 28 in the placebo group). The minocycline group had significant decreases in the SANS total sore, the PANSS total score and the PANSS negative symptoms score at week 16 compared to the placebo group. In addition, the minocycline group had a significant decrease in plasma levels of nitric oxide metabolites, but no significant difference in changes in plasma levels of IL-1 beta or TNF-alpha, compared to the placebo group at week 16. Further, the more decrease in plasma levels of nitric oxide metabolites was associated with less improvement in negative symptoms. Conclusion: The beneficial effect of adjunctive minocycline treatment on negative symptoms might be through mechanisms other than the nitric oxide pathway. The implications for future studies were discussed. (c) 2018 Published by Elsevier B.V.