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.

Study Overview

• Status: Completed
• Conditions: Schizophrenia Therapeutics
• Intervention / Treatment: Drug: Berberine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Tianjin, China
    • Tianjin Anding Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: control group
Experimental: berberine group	Drug: Berberine; Patients in the berberine group received berberine hydrochloride tablets (100 mg/tablet), three tablets three times daily.; Other Names: stable antipsychotic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the MCCB Overall Composite Score	MCCB is a standardized measurement tool for assessing cognitive function in schizophrenia. There are 9 subtests, which mainly assess 7 cognitive domains, including information processing speed, attention/alertness, Working memory, word learning, visual memory, reasoning and problem solving, and social cognition. After the evaluation is completed, the MCCB rough score is converted into the total score T score obtained after correction for age, gender, years of education, and untreated period. The T score is then converted into a defect score, with T scores ≥ 40, 35-39, 30-34, 25-29, 20-24, and ≤ 19 corresponding to defect scores 0, 1, 2, 3, 4, and 5, respectively. Among them, 1 represents mild defects, 2 represents mild to moderate defects, 3 represents moderate defects, 4 represents moderate to severe defects, and 5 represents severe defects. In this study, a defect score of ≥ 3 was used as the boundary for significant cognitive impairment.	changes within 0, 12weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of CRP	The concentration of C-reactive protein (CRP) is measured in venous blood. CRP is an acute-phase reactant protein synthesized by the liver, primarily functioning to recognize and clear pathogens or damaged cells. It plays a crucial role in inflammatory responses, infection surveillance, and disease monitoring.	changes within 0, 4, 8, 12weeks
Changes of Fecal Macrogene Sequencing(FMS)	Total genomic DNA was extracted from patient fecal samples and subjected to quality control. Qualified DNA was then randomly fragmented to approximately 350 bp using a Covaris ultrasonic disruptor to generate libraries, which were quantified by Qubit and qPCR. Following library QC, pooled libraries were sequenced on an Illumina NovaSeq platform (PE150). Raw sequencing data underwent quality control, followed by assembly and gene prediction to construct a non-redundant gene set. Genes were then annotated for taxonomic and functional classification and abundance statistics were computed. Statistical analyses, including similarity clustering, group ordination, and differential comparisons, were performed on samples and sample groups.	changes within 0, 12weeks
Change from baseline in scores on the remaining MCCB domains	MCCB is a standardized measurement tool for assessing cognitive function in schizophrenia. There are 9 subtests, which mainly assess 7 cognitive domains, including information processing speed, attention/alertness, Working memory, word learning, visual memory, reasoning and problem solving, and social cognition. After the evaluation is completed, the MCCB rough score is converted into the total score T score obtained after correction for age, gender, years of education, and untreated period.	changes within 0, 12weeks
Psychiatric Symptoms	The psychiatric symptoms of schizophrenia were assessed in all enrolled patients using the Positive and Negative Syndrome Scale (PANSS). The PANSS is a 30-item clinician-rated scale yielding a total score ranging from 30 (least symptomatic) to 210 (symptomatic), where higher scores indicate more severe psychopathology.	changes within 0, 4, 8,12weeks
Depressive Symptoms	The Hamilton Depression Scale-24 (HAMD-24) was used to assess the severity of depressive symptoms. Each item was scored on a scale of 0 (none) to 4 (severe); the total score ranged from 0 to 76, with higher scores indicating more severe depressive symptoms.	changes within 0, 4, 8,12weeks
Anxiety Symptoms	The Hamilton Anxiety Scale (HAMA) is used to assess the severity of anxiety symptoms. Each item is scored on a scale of 0 (none) to 4 (very severe), with a total score range of 0-56. Higher scores indicate more severe anxiety symptoms.	changes within 0, 4, 8, 12weeks
Changes in plasma levels of short-chain fatty acids.	Week 12 changes in plasma short-chain fatty acid levels from baseline.	changes within 0, 12weeks
Changes in plasma bile acid levels	Week 12 changes in plasma bile acid from baseline.	changes within 0, 12weeks
Changes in plasma tryptophan levels	Week 12 changes in plasma tryptophan from baseline.	changes within 0, 12weeks
Changes in glycolipid levels	Glucose and lipid levels were measured at Weeks 0, 4, 8, and 12.	Baseline, week 4, week 8 and week 12
Weight changes	Weight was measured at Weeks 0, 4, 8, and 12.	Baseline, week4, week8, week12

Collaborators and Investigators

• Sponsor: Tianjin Anding Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2023
• Primary Completion (Actual): January 30, 2026
• Study Completion (Actual): April 23, 2026

Study Registration Dates

• First Submitted: July 22, 2023
• First Submitted That Met QC Criteria: January 13, 2026
• First Posted (Actual): January 22, 2026

Study Record Updates

• Last Update Posted (Actual): June 30, 2026
• Last Update Submitted That Met QC Criteria: June 28, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: schizophrenia; Intestinal flora; berberine; cognitive symptoms
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Schizophrenia; Neurobehavioral Manifestations; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Alkaloids; Heterocyclic Compounds, 4 or More Rings; Benzylisoquinolines; Berberine Alkaloids; Berberine
• Other Study ID Numbers: BBR-SCH-2023

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No