Schizophrenia and brain inflammation: bystander or key player?

By Ana Espino | Published on August 21, 2025 | 2 min read


#Schizophrenia #Neuroinflammation #Cytokines  


Schizophrenia is a chronic and disabling psychiatric disorder, affecting about 1% of the global population. It manifests through disorganized thinking, impaired social and occupational functioning, and a marked reduction in quality of life. Biologically, schizophrenia is considered a multifactorial illness, resulting from complex interactions between genetic, neurodevelopmental, environmental, and immunological factors. Increasing evidence suggests that neuroinflammation may play a central role in this pathophysiology.  

Research has highlighted excessive activation of microglia, elevated pro-inflammatory cytokines, and disruptions of the blood–brain barrier, potentially contributing to neuronal network dysfunction and worsening of symptoms. The major challenge remains to determine whether this inflammation represents a causal mechanism, an aggravating factor, or a secondary consequence of the disease and its treatments. In this context, the study was initiated to explore the role of neuroinflammation in schizophrenia and assess its diagnostic and therapeutic implications.    

Inflammation: mere reflection or true driver?

This study combines clinical, biological, and imaging approaches to better understand the potential role of neuroinflammation in schizophrenia. Post-mortem studies allow for direct analysis of brain tissues. Neuroimaging techniques have made it possible to assess in vivo inflammatory activity and its relationship with symptom severity. The study of peripheral biomarkers such as cytokines and acute-phase proteins in blood or cerebrospinal fluid has provided indirect measures. Finally, genetic and transcriptomic data were analyzed to identify variations associated with immuno-inflammatory pathways.  

Findings show increased microglial activation in several brain regions of patients with schizophrenia. Biological analyses reveal persistently elevated levels of pro-inflammatory cytokines (IL-6, TNF-α, IL-1β), correlated with symptom severity. Genetic studies identify polymorphisms related to immune-inflammatory pathways, suggesting a hereditary vulnerability. The integrity of the blood–brain barrier appears compromised, allowing infiltration of peripheral immune cells. Clinically, some patient subgroups display a pronounced inflammatory phenotype, associated with poorer response to conventional antipsychotics and more severe progression. Pilot therapeutic trials with anti-inflammatory agents (NSAIDs, minocycline, tocilizumab) show mixed but encouraging results, suggesting potential clinical benefit.    

Neuroinflammation and schizophrenia: toward new targets?

Schizophrenia remains a complex and disabling condition, with an etiology that extends beyond the dopaminergic hypothesis alone. A major current challenge lies in integrating the inflammatory dimension into this multifactorial model. The objective of this review was to clarify the role of neuroinflammation. Results suggest that neuroinflammation is a significant contributing mechanism, influencing both symptoms and therapeutic response.

However, existing studies are limited by methodological heterogeneity, the cross-sectional nature of many investigations, and the absence of standardized biomarkers to define an “inflammatory phenotype” in schizophrenia. Future research must focus on developing robust biomarkers, conducting longitudinal studies, and testing targeted anti-inflammatory therapies on a larger scale—paving the way for a more personalized approach in the management of schizophrenia.      

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