Immunomodulation as Therapeutic Approach in Schizophrenia and Depression: State of the Art

Abstract

Infl ammation has been discussed for decades as an underlying cause of psychiatric disorders such as major depression (MD) and schizophrenia. Almost a hundred years ago, an anti-infl ammatory therapeutic approach, so-called vaccination therapy, was proposed by Wagner von Jauregg. In schizophrenia and MD, opposite patterns of the type-1 and type-2 immune response seem to be associated with differences in the activation of the enzyme indoleamine 2,3-dioxygenase (IDO) and in tryptophan-kynurenine metabolism. These differences are associated with an imbalance in glutamatergic neurotransmission, which may contribute to an excess of N -methyl-D -aspartate (NMDA) agonism in depression and NMDA antagonism in schizophrenia. In both schizophrenia and depression the immunological imbalance results in increased prostaglandin E 2 (PE 2 ) production and probably also in increased cyclooxygenase-2 (COX-2) expression. Although there is strong evidence for the view that the interactions of the immune system, IDO, serotonergic system and glutamatergic neurotransmission play a key role in schizophrenia and depression, several gaps remain that need to be closed by intense research. Accordingly, anti-infl ammatory or immune-modulating substances might have benefi cial effects in schizophrenia and MD. COX-2 inhibitors have shown encouraging results in animal models. Moreover, during the last decade many clinical studies have been performed with COX-2 inhibitors, mostly celecoxib, in schizophrenia and MD. For ethical reasons, all these studies used an add-on design, i.e. the COX-2 inhibitor was given adjunctive to either antipsychotics (in schizophrenia) or antidepressants (in MD). Although an add-on design is a methodological challenge, favourable effects of COX-2 inhibitors were observed in placebo-controlled double-blind studies in both indications. Meta-analytic studies proved a signifi cant therapeutic effect of COX-2 inhibitors in MD and in early stages of schizophrenia. Other pharmacological approaches based on N. Müller (*) Department of Psychiatry and Psychotherapy , Ludwig-Maximilians University Munich , Nussbaumstr. 7 , 80336 Munich , Germany e-mail: Norbert.Mueller@med.uni-muenchen.de 352 immunological effects are discussed. Anti-infl ammatory and immune-modulating compounds are promising but still need careful further scientifi c evaluation, including clinical studies in larger samples of patients.

The Role of Intercellular Adhesion Molecule-1 in the Pathogenesis of Psychiatric Disorders

“…Ex vivo neuroimaging, e.g., positron emission tomography, may be able to provide additional information in answer to these questions, but to date, no ligand for ICAM has been developed. The differences in the neuroinflammatory process between disorders may also explain why anti-inflammatory treatment has beneficial therapeutic effects in some psychiatric disorders, such as MDD and schizophrenia (Müller, 2015), and prophylactic effects in dementia (Müller et al, 2015).…”

Treatment-Resistant Depression Revisited: A Glimmer of Hope

“…The adjunctive use of CBX has been positive in that it enhanced the response of antidepressants with overall good tolerability and safety. Agents used concurrently have included fluoxetine, reboxetine, sertraline and mood stabilizers [ 210 , 211 , 212 , 213 ]. The adjunctive treatment of CBX with an antidepressant has also been shown to be beneficial in BD patients, as demonstrated by the study of Nery et al and our own study with treatment-resistant bipolar depressed patients given escitalopram and CBX [ 214 , 215 ].…”

Neuroinflammation in Schizophrenia: A Critical Review and The Future

“…Various clinical therapeutic studies based on the anti-inflammatory approach show promising results. The COX-2 inhibitor celecoxib showed favorable results in several studies 41 . Laan et al showed that 3 month adjuvant aspirin treatment reduced the total and positive scores on the Positive and Negative Syndrome Scale (PANSS) compared to the placebo group even if it could not improve the cognitive function in schizophrenic patients 42 .…”