Association between Peripheral α-Defensins and Schizophrenia: A Systematic Review

Abstract

Background: Schizophrenia is a complex neuropsychiatric disorder whose pathophysiology extends beyond classical neurotransmitter dysfunction to include immune and inflammatory mechanisms. Among emerging biomarkers, peripheral α-defensins have attracted attention because of their role in innate immunity. Objective: To systematically summarize the available evidence regarding the association between peripheral α-defensins and schizophrenia and to assess their potential as neuroimmune biomarkers. Methods: A systematic review was conducted following the PRISMA 2020 guidelines. PubMed, Scopus, and the Cochrane Library were searched using terms related to schizophrenia, α-defensins, biomarkers, inflammation, and innate immunity. Observational studies involving human participants that evaluated peripheral α-defensins were included. Results: A total of 1,205 records were identified, but only one study met the predefined eligibility criteria. This study reported significantly increased peripheral α-defensin levels in patients with schizophrenia and intermediate concentrations in unaffected monozygotic twins, suggesting that these peptides may reflect biological susceptibility rather than disease activity alone. Indirect evidence involving other defensins further supports the contribution of innate immune dysregulation to severe mental disorders. Conclusions: Peripheral α-defensins appear to be promising candidate biomarkers for schizophrenia; however, current evidence remains scarce and is insufficient for clinical application. Additional well-designed prospective, multicenter, and longitudinal studies are required to validate their diagnostic and prognostic value and to clarify their role in the neuroimmune mechanisms underlying schizophrenia.