The Role of Inflammation in the Treatment of Schizophrenia

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 In addition, other published and unpublished data were included in another meta-analysis that concluded the significant effect of add-on celecoxib in positive symptoms in first episode patients.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.

Regulation of Reactive Oxygen Species-Mediated Damage in the Pathogenesis of Schizophrenia

“…Indeed, some antioxidants such as vitamins and essential polyunsaturated fatty acids have been shown to ameliorate the symptoms of schizophrenia [ 144 , 145 , 146 ]. Moreover, several studies have reported that schizophrenia can be treated with a combination of dietary supplementation, adjuvant antioxidant therapy, and antipsychotic medication [ 147 , 148 ].…”

Anti-Inflammatory Diets and Schizophrenia

“…In the central nervous system (CNS), inflammation may be neuroprotective or neurotoxic depending on the interactions among genetic variations, environmental factors, and inflammatory responses [ 17 ]. Recent evidence regarding inflammation and schizophrenia suggests that inflammation is a possible risk factor to induce schizophrenia and to aggravate its symptoms [ 16 18 19 20 ]. The levels of pro-inflammatory cytokines including interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-1β, IL-12, and transforming growth factor (TGF)-β were elevated in subjects with schizophrenia [ 21 22 ].…”

Concordance of Immune-Related Markers in Lymphocytes and Prefrontal Cortex in Schizophrenia

“…During the last 50 years, clinical neuroimaging and molecular studies suggest that immune dysfunction is one of the factors contributing to the pathogenesis of schizophrenia. 56 , 57 Mounting evidence shows that inflammation has a potential role in the development and maintenance of the disease 58–61 and immune and inflammatory mediators could serve as potential biomarkers for schizophrenia. 1 , 62 One hypothesis is that immune alterations observed in the CNS could originate from changes in the peripheral immune system.…”