European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology · 2025
Blood-based biomarkers of neuroaxonal and astroglial injury identify ultra-treatment-resistant schizophrenia.
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de Oliveira Caio Andrade, Pinto Joel Porfirio, de Pinho Carolina Saraiva Nunes, Soares Michelle Verde Ramo, Silva Maria Francilene Souza, Lucena David Freitas, Braga-Neto Pedro, Campos Eugênio de Moura, Sanders Lia Lira O, Frota Annyta Fernandes, Macedo Danielle S
Аннотация
BACKGROUND: Ultra-treatment-resistant schizophrenia (UTRS) is the most severe subtype of treatment refractoriness, with persistent symptoms despite clozapine use. Although immunoinflammatory mechanisms have been implicated in schizophrenia, the biological basis of UTRS remains unclear. We hypothesized that blood-based biomarkers of astroglial and neuroaxonal injury could distinguish UTRS from other schizophrenia subtypes and healthy controls.
METHODS: Plasma levels of glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), ubiquitin C-terminal hydrolase L1 (UCH-L1), and total tau were measured using the Quanterix Neurology 4-Plex A assay. Participants included individuals with treatment-sensitive schizophrenia (TSS, n = 11), treatment-resistant schizophrenia (TRS, n = 13), UTRS (n = 10), and healthy controls (n = 15), recruited from an outpatient psychiatric service in Brazil. Group differences were assessed using univariate analyses. ROC curves evaluated the discriminative performance of each biomarker.
RESULTS: Patients with UTRS exhibited significantly higher levels of GFAP, NfL, and UCH-L1 compared to controls (p < 0.05). TSS and TRS showed intermediate values. Total tau was elevated only in TRS. ROC analysis revealed excellent accuracy for GFAP (AUC = 0.913) and good performance for NfL and UCH-L1 (AUCs > 0.85) in distinguishing UTRS from controls.
CONCLUSIONS: UTRS is associated with a distinct peripheral biomarker profile reflecting astroglial and neuroaxonal injury. Plasma levels of GFAP and NfL, measured via ultrasensitive assays, may serve as promising biomarkers for identifying ultra-resistant schizophrenia and guiding precision psychiatry strategies.
METHODS: Plasma levels of glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), ubiquitin C-terminal hydrolase L1 (UCH-L1), and total tau were measured using the Quanterix Neurology 4-Plex A assay. Participants included individuals with treatment-sensitive schizophrenia (TSS, n = 11), treatment-resistant schizophrenia (TRS, n = 13), UTRS (n = 10), and healthy controls (n = 15), recruited from an outpatient psychiatric service in Brazil. Group differences were assessed using univariate analyses. ROC curves evaluated the discriminative performance of each biomarker.
RESULTS: Patients with UTRS exhibited significantly higher levels of GFAP, NfL, and UCH-L1 compared to controls (p < 0.05). TSS and TRS showed intermediate values. Total tau was elevated only in TRS. ROC analysis revealed excellent accuracy for GFAP (AUC = 0.913) and good performance for NfL and UCH-L1 (AUCs > 0.85) in distinguishing UTRS from controls.
CONCLUSIONS: UTRS is associated with a distinct peripheral biomarker profile reflecting astroglial and neuroaxonal injury. Plasma levels of GFAP and NfL, measured via ultrasensitive assays, may serve as promising biomarkers for identifying ultra-resistant schizophrenia and guiding precision psychiatry strategies.