Berberine Improving Cognitive Impairments in Schizophrenia

Study on the Mechanism s of Berberine Improving Cognitive Impairments in Schizophrenia Based on Gut-brain Axis

This study is a 12-week, randomized, blank-controlled, assessor-blinded trial. Eligible patients were randomized in a 1:1 ratio to receive either berberine hydrochloride or blank control as an add on to their stable antipsychotic regimen for 12 weeks. Randomization was performed using a computer-generated random number table, and allocation was concealed using sequentially numbered, opaque, sealed envelopes. The trial included four visits: baseline (visit 1), week 4 (visit 2), week 8 (visit 3) and week 12 (visit 4). Patients in the berberine group received berberine hydrochloride tablets (100 mg/tablet), three tablets three times daily. The control group received no intervention (blank control) and continued their usual care.

Psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS); cognitive symptoms were evaluated using the MATRICS Consensus Cognitive Battery (MCCB); depressive symptoms were assessed using the 24-item Hamilton Depression Rating Scale (HAMD-24); and anxiety symptoms were evaluated using the Hamilton Anxiety Rating Scale (HAMA). All assessments were administered by trained research personnel. The MCCB assessment was performed only at baseline and Week 12, whereas the PANSS, HAMD, and HAMA assessments were conducted at baseline, Week 4, Week 8, and Week 12. The primary outcome measure was the uncorrected T-score of the MCCB Overall Composite Score, which was derived by standardizing and summing the T-scores across seven cognitive domains: processing speed, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. Since commercially available berberine is only formulated as yellow tablets with a marked bitter taste, which makes it difficult to prepare an indistinguishable placebo, a blank control design was adopted to maintain feasibility while ensuring the integrity of the study. We acknowledge that this open-label design may introduce potential placebo effects. Nevertheless, the cognitive assessments are less susceptible to expectancy effects, and both the raters and statisticians were blinded to group assignment to minimize bias.

Inclusion Criteria:

• a diagnosis of SCZ according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5);
• receiving stable doses of antipsychotic medication for at least 1 month before enrollment;
• age between 18 and 65 years;
• provision of written informed consent by patients and their families.

Exclusion Criteria:

• a current diagnosis of any other DSM-5 psychiatric disorder;
• presence of severe physical illness;
• receipt of physical treatments such as repetitive transcranial magnetic stimulation or modified electroconvulsive therapy within one month prior to enrollment;
• hemolytic anemia or glucose-6-phosphate dehydrogenase (G6PD) deficiency;
• pregnant and lactating women;
• any factor that would interfere with the participant's ability to provide informed consent or complete the study.