COX-2 inhibition as a treatment approach in schizophrenia: Immunological considerations and clinical effects of celecoxib add-on therapy

Abstract

Recent advances in immunological research regarding the differentiation between the type-1 and type-2 immune response are discussed. Increased levels of Interleukin-6 (IL-6) and the activation of the IL-6 system in schizophrenia might be the result of the activation of type-2 monocytes/macrophages, too. On the contrary, several parameters of the specific cellular immune system are blunted, e. g. the decreased type-1 related immune parameters in schizophrenic patients. This study was performed as a double-blind, placebo-controlled, randomized evaluation of risperidone and celecoxib versus risperidone and placebo. Fifty schizophrenic patients were included in the study: 25 patients received risperidone and placebo, and 25 patients received risperidone and celecoxib for 5 weeks after the wash-out period. The treatment effect was calculated by ANCOVA. In parallel, serum levels of sTNF-R1 and sIL- 2R, and the percentages of CD3(+)-, CD4(+)-, and CD19(+) lymphocytes were estimated. As expected, both groups of schizophrenic patients showed significant improvement. However, the celecoxib add-on therapy group showed a significant group effect in the PANSS total score. The cytokines and lymphocytes reflected the type-1/type-2 balancing effects of COX-2 inhibitors. Additional treatment with celecoxib has significant positive effects on the therapeutic action of risperidone with regard to the total schizophrenia psychopathology. Moreover, the fact that treatment with an immunomodulatory drug shows beneficial effects on the symptomatology of schizophrenia indicates that immune dysfunction in schizophrenia is not just an epiphenomenon, but related to the pathomechanism of the disorder.

A Cyclooxygenase-2 Inhibitor Ameliorates Behavioral Impairments Induced by Striatal Administration of Epidermal Growth Factor

“…Thus, cytokine-mediated inflammatory reactions may in certain circumstances evoke psychiatric symptoms. Based on this hypothesis, preclinical trials of nonsteroidal anti-inflammatory drugs on patients with schizophrenia are underway (Muller et al, 2002(Muller et al, , 2004Riedel et al, 2005). Tetracycline, an antibiotic that possesses anti-inflammatory activity, improves the positive and negative syndrome scale (PANSS) of schizophrenia patients (Miyaoka et al, 2007).…”

Neuroinflammation in Schizophrenia Focused on the Pharmacological and Therapeutic Evidence

“…The same authors also reported beneficial effects of celecoxib add-on therapy on cognitive symptoms in schizophrenia patients 155 . But the subsequent studies by other groups reported inconsistent results.…”

Tumor necrosis factor promoter haplotype associated with schizophrenia reveals a linked locus on 1q44

“…46 Clinical reports on the beneficial effects of the antiinflammatory COX-2 inhibitors in combination with the regular antipsychotic treatment on the total schizophrenia psychopathology provide additional evidence that the immune dysfunction seen in schizophrenics may be part of the etiology and/or pathophysiology of the disorder. 47,48 In light of the immunological theory of schizophrenia, the MHC has long been proposed as a candidate locus that may influence the susceptibility to schizophrenia. The MHC spans approximately 4 million base pairs of DNA and has been mapped to 9 Linkage studies have also suggested that there may be at least one locus on chromosome 6p that affects susceptibility to schizophrenia, [10][11][12][13][14] eye-tracking dysfunction, 15 and/or the severity of positive symptoms.…”