Abstract
Background: Inflammation plays a major role in the onset and maintenance of schizophrenia. The objective of the present work was to synthetize in a narrative review the recent findings in the field of inflammation in schizophrenia and their application in daily practice.Method: This review was based on the most recent meta-analyses and randomized controlled trials.Results: The disturbed cytokines depend on the phase of the illness. A meta-analysis of cytokines in schizophrenia found higher levels of pro-inflammatory and anti-inflammatory cytokines in the peripheral blood in both patients with first-episode schizophrenia and relapsed patients than in healthy controls. Exploring detailed data on immune-inflammatory disturbances in SZ reveals that IL-6 is one of the most consistently disturbed cytokines. Other cytokines, including IL1, TNF, and IFN, are also disturbed in schizophrenia. Choosing a broad spectrum anti-inflammatory agent that may inhibit subsequent pathways might be particularly useful for the treatment of inflammatory schizophrenia. Highly sensitive C-Reactive Protein is a useful screening marker for detecting inflammation in SZ subjects. Anti-inflammatory agents have shown effectiveness in recently published meta-analyses. Only one study found a significant difference between celecoxib and placebo, but two found a trend toward significance on illness severity and one on positive symptoms. In addition, other published and unpublished data were included in another meta-analysis that concluded the significant effect of add-on celecoxib in positive symptoms in first episode patients. There is a lack of data to determine if aspirin is truly effective in schizophrenia to date. Other anti-inflammatory agents have been explored, including hormonal therapies, antioxidants, omega 3 fatty acids, and minocycline, showing significant effects for reducing total, positive, and negative score symptoms and general functioning. However, each of these agents has multiple properties beyond inflammation and it remains unclear how these drugs improve schizophrenia.Conclusion: The next step is to tailor anti-inflammatory therapy in schizophrenia, with two main challenges: 1. To provide a more efficient anti-inflammatory therapeutic approach that targets specific pathways associated with the pathology of schizophrenia. 2. To develop a more personalized approach in targeting patients who have the best chance of successful treatment.
Highlights
Though conventional treatments have improved schizophrenia prognosis, they and the response rate of antipsychotics in schizophrenia remain unsatisfactory
Neuromediator alterations classically described in schizophrenia have been identified in low-level neuro inflammation and may be key triggers of schizophrenia symptoms onset and maintenance [4]
IL-6 is the most consistent increased cytokine in all phases of schizophrenia, but a large bundle of other cytokines is found to be disturbed. These findings suggest that choosing a broad-spectrum anti-inflammatory agent that may inhibit subsequent pathways may be useful for the treatment of inflammatory schizophrenia
Summary
Though conventional treatments have improved schizophrenia prognosis, they and the response rate of antipsychotics in schizophrenia remain unsatisfactory. Antipsychotics are effective on positive symptoms but unsatisfactory on negative/depressive symptoms, social functioning, and quality of life [1] An explanation for this high rate of non-response and relapses relies on the observation that current pharmacological treatments are primarily based on the monoaminergic hypothesis, without involving the personalized medicine approach. According to this hypothesis, schizophrenia is principally due to a dopamine dysfunction in the brain (with an excess in the striatum ventral tegmental area and a deficit in the prefrontal cortex). The antipsychotic that has shown the best effectiveness, has one of the lowest potentials to reduce dopamine in the brain [2] The objective of the present work was to synthetize in a narrative review the recent findings in the field of inflammation in schizophrenia and their application in daily practice
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