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

The Scale for Assessment of Negative Symptoms (SANS) is a clinician-rated observational scale developed by American neuropsychiatrist Nancy C. Andreasen to assess negative symptoms in schizophrenia. The scale includes categories such as alogia (poverty of speech), blunted affect, avolition, anhedonia/asociality, and attention impairment, with a focus on evaluating the patient's deficit symptoms of mental activity. Changes in the total SANS score will, to a certain extent, reflect changes in the severity of the subject's negative symptoms.

In this study, the Skin Flush Meter will be utilized for the first time to quantify the attenuation of the niacin flush response, serving as an objective assessment tool for negative symptoms in schizophrenia (SZ). Building upon a pre-existing image library of niacin flush responses from a previous cohort, the research team from our collaborating unit has developed a niacin predictor device. This device largely preserves the observational steps of the original method. Based on this, previously manual simple scoring has been replaced with artificial intelligence (AI) for processing large volumes of color images. It compares pre- and post-niacin color differences in the skin, extracts variables for erythema intensity, and precisely calculates the area of irregular redness. By integrating the temporal dimension, it further achieves quantification and refinement with second-level resolution.

All participants underwent cognitive function assessment based on the MATRICS Consensus Cognitive Battery (MCCB). 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.

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.

The Clinical Global Impression (CGI) scale is a standardized tool used to assess the severity of a patient's illness and the effectiveness of treatment. The CGI employs a 1 to 7 point graded rating scale, with two subscales: Clinical Global Impression of Severity (CGI-S) and Clinical Global Impression of Improvement (CGI-I). Higher CGI-S scores indicate greater illness severity. CGI-I is calculated as the difference between post-treatment and pre-treatment assessments; a higher score signifies more significant illness improvement.

The Calgary Depression Scale for Schizophrenia (CDSS) is primarily utilized to evaluate depressive symptomatology in patients with schizophrenia. The scale consists of 9 structured items that assess: depressive mood, despair, self-deprecation, delusions of guilt, pathological guilt, diurnal variation (morning depression), early morning awakening, suicidal ideation, and observed depressive signs. Each item is rated on a 0-3 point scale, where higher scores signify increased symptom severity.

The Global Assessment of Functioning (GAF) Scale for individuals with schizophrenia is a specialized instrument for evaluating their functional capacity. Its purpose is to comprehensively assess the patient's functional performance in various significant life areas, such as social, occupational, and psychological functioning, as well as activities of daily living. The scale's scoring ranges from 0-100:

A score of ≥ 71: Suggests generally normal social functioning, enabling regular engagement in work, study, and social activities.

A score of 51-70: Implies mild impairment in social functioning, possibly characterized by diminished social interactions or reduced responsibility.

A score of 31-50: Denotes significant impairment in social functioning, necessitating ongoing supervision or supportive assistance for daily living.

A score of ≤ 30: Signifies severe impairment in social functioning, requiring professional therapeutic or custodial care.

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.

Fresh morning stool samples were collected from subjects at baseline, 12 weeks, or study termination using a 5ml sterile, sealed stool collection kit. Care was taken to collect from the center of the sample, avoiding contact with the external environment to prevent contamination. Within 15 minutes of collection, samples were divided into two 2ml EP tubes and stored at -80°C for fecal 16S rRNA sequencing.