Association between clinical remission in schizophrenia and immunological biomarkers: a systematic review.

OBJECTIVE

Schizophrenia involves complex interactions between genetic, neurobiological, and environmental factors, with immuno-inflammatory processes and oxidative stress playing central roles in its pathophysiology. Despite evidence linking these pathways to disease course, the specific relationship between clinical remission and immunological biomarkers remains underexplored. This systematic review aimed to investigate the association between clinical remission in individuals with schizophrenia and immune system markers, including inflammatory and oxidative stress indicators.

METHODS

This systematic review followed PRISMA guidelines, searching Scopus, PubMed, BVS, Web of Science, and PsycINFO from 2005-2024 for observational studies (cross-sectional, case-control, cohort) in English. Inclusion criteria required evaluation of schizophrenia patients, comparison of remitted versus non-remitted groups using RSWG or equivalent criteria, and assessment of immunological biomarkers and oxidative stress markers.

RESULTS

Twenty-two studies met inclusion criteria. Fifteen studies found inflammatory biomarker alterations: neutrophil-to-lymphocyte ratio (NLR) reduction in remission versus relapse/stability periods; higher hsCRP, lower IL-33/sST2 in remission; baseline TNF-α reductions predicting remission; IL-6 decreases correlating with white matter improvements; higher baseline neutrophil gelatinase-associated lipocalin (NGAL) levels and complement pathway proteins such as C4A. Four studies on oxidative stress showed increased SOD/TAC activity and reduced biopirines/AOPP in remission versus acute phases, though some markers like erythrocyte SOD remained persistently altered.

CONCLUSIONS

Clinical remission in schizophrenia appears to be associated with changes in selected peripheral inflammatory and oxidative stress biomarkers, although further prospective longitudinal studies are needed.