Unravelling immune alterations in schizophrenia: can DNA methylation provide clues?

Abstract

Several lines of evidence indicate that immune and inflammatory alterations are implicated in the pathophysiology of schizophrenia. There are studies showing higher incidence of various autoimmune disorders, with the exception of rheumatoid arthritis, in schizophrenia patients and their first-degree relatives [1]. Epidemiological studies have also provided that maternal infections with Toxoplasma gondii, influenza virus, herpes simplex virus and rubella virus increase the risk of schizophrenia in offspring [2]. These clinical and epidemiological data have provided grounds for investigating biological underpinnings of immune deregulation in schizophrenia. It has been shown that patients with schizophrenia have altered plasma levels of cytokines, increased levels of acute-phase proteins, elevated titers of various specific and nonspecific autoantibodies, abnormal blood counts of immune cells, especially lymphocytes, and activated microglia in the CNS [3]. Interestingly, some immune and inflammatory alterations may serve as schizo phrenia markers. The recent meta-analysis [4] of cytokine alterations in schizophrenia revealed that IL-1β, IL-6 and TGF-β serve as state-related markers of schizophrenia as they are increased during acute exacerbations and prone to normalize with antipsychotic treatment. On the other hand, IL-12, IFN-γ, TNF-α and soluble IL-2 receptor might be trait markers of schizophrenia, as they are elevated during acute exacerbations and following antipsychotic treatment. These cytokine alterations might also be the consequence of the imbalance between Th1 and Th2 lymphocytes towards the predominance of Th1