Serum and plasma glial fibrillary acidic protein in patients with schizophrenia: A systematic review and meta-analysis.

Abstract

Background: Schizophrenia is a neurodevelopmental disorder with a progressive course that typically begins in late adolescence or early adulthood. Glial fibrillary acidic protein (GFAP), a key component of the astrocyte cytoskeleton, has been linked to schizophrenia, with abnormal GFAP levels observed in both brain tissue and peripheral blood samples. This study aims to systematically review and meta-analyze GFAP levels in schizophrenia patients to assess its potential as a biomarker of astrocytic damage.

Methods: We systematically searched PubMed, Scopus, and Web of Science up to April 23, 2025, for studies reporting blood GFAP levels in patients with schizophrenia and healthy controls. Eligible studies included human participants, with GFAP measured in serum or plasma and results reported as summary statistics or extractable from graphs. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. Effect sizes were calculated using Hedges' g. Due to high heterogeneity (I² > 50%), a random effects model was applied. Heterogeneity was assessed using the I² statistic, and publication bias was evaluated through funnel plots and Egger's and Begg's tests.

Results: A total of 164 records were identified through database searches. After removing duplicates, 118 records were screened based on title and abstract, and 12 studies underwent full-text screening. Eight studies were ultimately included. The studies included 854 participants, with an age range from 24 to 45 years. GFAP levels in schizophrenia patients were significantly higher compared to healthy controls (SMD = 0.74, 95% CI [0.15, 1.33], p = 0.01; I² = 93.68%). Removing two specific studies one at a time rendered the results insignificant, while excluding other studies individually did not affect significance. Publication bias was suggested by Begg's test and Egger's test (p < 0.05). Quality assessment indicated low risk of bias in most domains, though most of the studies had high risk due to insufficient reporting on patient enrollment and blinding of laboratory technicians.

Discussion: Our findings suggest a significant difference in GFAP levels in patients with schizophrenia and indicate a potential role for GFAP in astrocytic pathology in these patients. Nonetheless, additional well-designed studies with larger sample sizes and rigorous methodologies are still needed to fully clarify its clinical relevance.