Berberine improves negative symptoms and cognitive function in patients with chronic schizophrenia via anti-inflammatory effect: a randomized clinical trial

BACKGROUND: Based on the neuroinflammation hypothesis in schizophrenia and known anti-inflammatory effects of berberine, the aim of the present study is to investigate the efficacy of berberine in treating negative symptoms and cognitive deficits in adult patients with chronic schizophrenia. METHODS: Enrolled participants were randomized to receive berberine or placebo for 3 months. The Scale for the Assessment of Negative Symptoms (SANS), Trail-making Test A (TMT-A), Trail-making Test B (TMT-B), and Hopkins Verbal Learning Test (HVLT) were used to evaluate the negative symptoms and cognitive function at four-time points (baseline, 1st, 2nd, and 3rd month). Serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were used as inflammatory markers. 106 patients with per-protocol were analyzed, 56 in the experimental (berberine) group and 50 in the control (placebo) group. RESULTS: From baseline to month 3, patients receiving berberine demonstrated a decrease in total scores on clinical scales SANS, TMT-A and TMT-B and showed a serum level reduction of IL-1β, IL-6 and TNF-α comparing with patients in the control group (P < 0.05). There were positive correlations between the change of serum IL-1β level and the change of SANS (r = 0.210, P = 0.039), TMT-A (r = 0.522, P < 0.001), and TMT-B (r = 0.811, P < 0.001); between the change of serum IL-6 level and the change of TMT-A (r = 0.562, P < 0.001), and TMT-B (r = 0.664, P < 0.001); between the change of serum TNF-α level and the change of TMT-B (r = 0.472, P < 0.001) after berberine treatment. CONCLUSIONS: Berberine is an anti-inflammatory agent that can potentially mitigate the negative symptoms and cognitive deficits in patients with schizophrenia.