Anti inflammatory agents in schizophrenia? Progr Neuro-Psychopharm & BiolPsy. March 2013

Despite progress in various modalities of  interventions ( pharmacological, social and  psychological ), one third of schizophrenia patients show a chronic course.Genetic studies show that different gene loci located on chromosome 6p22.1 are the most probable susceptibility genes for schizophrenia.This region includes several genes of interest that are related to immune function . It is thought that the immune response  from a variety of causes might be determining the risk for schizophrenia.

It is also thought that gultamatergic hypo function might be causing dopaminergic dysfunction in schizophrenia.  It is shown that the function of glutamate system is linked to immune systems.

Miller et al’s metaanalysis (2011) showed that in acutely relapsed inpatients, showed significantly higher levels of  cytokines (IL-6, TNF-α, IL-8, TGF-β, IL-1RA and IFN-γ) compared to controls.Studies also indicate that different immune profiles may prevail at different stages of schizophrenia. The two types of immune system ( type 1: promotes the cell-mediated immune response directed against intracellular pathogens.  Type 2:  production of antibodies directed against extra- cellular pathogens) might be differentially involved.Some evidence supports that antipsychotic treatment activates type 1 response and probably decrease type 2 response.They might be exerting  a balancing effect.The type 1/type 2 imbalance in the CNS seems to be represented by the imbalance between the activation of microglial cells and astrocytes.Increased levels of S100 B ( a marker of astrocyte activation) in schizophrenia suggest over activation of astrocytes.

Second trimester infection is known to increase the risk of schizophrenia. It may be that the immune response , not the infection itself, may be the culprit. In animal models, immune activation of the mother during the second trimester of pregnancy led to schizophrenia-like symptoms in the offspring in adulthood in a series of studies (Meyer et al., 2011).

Several studies have shown that unmedicated schizophrenia patients have a significantly higher number of monocytes than healthy controls .PET studies have  shown microglial activation in schizophrenia.

What about immune modulation based treatments?

omega 3 fatty acids: Results are inconsistent and the overall effect size is small in comparison with placebo in first-episode and chronic schizophrenia.In high risk group, transition to psychosis was reduced by omega 3 fatty acids.

Erythropoetin: May help to improve cognitive symptoms.

Minocyclin:  Antibiotic with anti-inflammatory action, shown to be effective as an add on agent.

Celecoxib ( Cox 2 inhibitor):Therapeutic effect  was observed in a prospective, randomized, double-blind study as an add-on to risperidone in acute exacerbation of schizophrenia.Increased type 1 immune response was found in the treatment group. Add on celecoxib to amisulpride was also found to be beneficial in early stage of illness.

Summary of the article:

Anti-inflammatory treatment in schizophrenia .Norbert Müller , Aye-Mu Myint, Daniela Krause, Elif Weidinger, Markus J. Schwarz. Progress in Neuro-Psychopharmacology & Biological Psychiatry 42 (2013) 146–153

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