Berberine in Treating Negative Symptoms of Schizophrenia: Clinical Efficacy and Mechanisms

"Negative" symptoms are a major challenge for people with schizophrenia (SZ) and are a key reason why they struggle with everyday functioning. While current medications work well for the "positive" symptoms (like hallucinations or delusions), they aren't very effective at improving these "negative" symptoms, which include things like a lack of motivation or emotion. This study is designed as a large-scale, randomized, placebo-controlled, rater-blinded trial to investigate whether berberine (BBR), a chemical compound, can safely and effectively ameliorate negative symptoms in patients with schizophrenia (SZ). The investigators will also explore the effects of BBR on gut microbiota, related fecal metabolites, and systemic inflammatory status. By comparing these various biomarkers before and after BBR adjunctive treatment, the investigators aim to elucidate the mechanism of action of BBR on negative symptoms and to identify its primary therapeutic targets. This study is expected to open up novel therapeutic avenues for the treatment of negative symptoms in schizophrenia in the future.

Inclusion Criteria: * Subjects met the diagnostic criteria for schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). The diagnosis was confirmed by two psychiatrists who interviewed enrolled patients using the Structured Clinical Interview for DSM-5 Disorders, Clinician Version (SCID-5-CV). * Age between 18 and 60 years, inclusive. * Gender: Not restricted. * Ethnicity: Han Chinese. * Subjects were receiving a stable dose of antipsychotic medication for at least 3 months prior to enrollment and had no dose adjustments in the month preceding enrollment. * Subjects exhibited significant negative symptoms, defined as: A total score of ≤ 70 on the Positive and Negative Syndrome Scale (PANSS). Scores of ≤ 4 on the PANSS items for delusions, conceptual disorganization, hallucinations, and excitement. A score \> 0 on the Negative Symptom Subscale-Positive Symptom Subscale. * The patient or their legal representative provided informed consent and signed the informed consent form agreeing to participate in the study. Exclusion Criteria: * Individuals meeting DSM-5 criteria for other psychiatric disorders. * Current severe neurological disease, uncontrolled metabolic disease, infectious disease, or autoimmune disease. * History of gastrointestinal surgery. * Use of antibiotics, other immunomodulatory agents, hormones, microecological agents, or probiotic medications within the past 1 month. * Allergy to BBR (if "BBR" is a known abbreviation, otherwise it should be spelled out or defined). * Receipt of physical therapies such as electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) within the past 1 month. * Individuals with hemolytic anemia and glucose-6-phosphate dehydrogenase (G6PD) deficiency. * Pregnant or lactating females. * Any factor that would prevent the participant from providing informed consent or participating in the study.