COX-2 Inhibitors, Aspirin, and Other Potential Anti-Inflammatory Treatments for Psychiatric Disorders

Abstract

Inflammatory processes associated with persistent (chronic) infection have long been discussed as etiological factors in psychiatric disorders. Studies have found that people with major depression have higher levels of pro-inflammatory cytokines, for example, IL-1, IL-6, and tumor necrosis factor-alpha, and C-reactive protein. In schizophrenia, many reports have described raised levels of cytokines, for example, IL-6; and meta-analyses have confirmed these findings. Microglia cells are important in inflammatory processes, and positron emission tomography studies have shown microglia activation in both depression and schizophrenia.As a consequence of the above findings, immunomodulation is widely discussed as a potential treatment approach in both major depression and schizophrenia. The COX-2 inhibitor celecoxib was found to have a significant positive effect on major depression, not only in single studies but also in meta-analyses. Celecoxib has also been studied in schizophrenia and has shown efficacy, in particular, in early disease stages. The mixed COX inhibitor aspirin (acetylsalicylic acid) seems to have both protective and therapeutic effects on schizophrenia.This paper discusses the hypothesized role of inflammation in major depression and schizophrenia, including markers of inflammation; pertinent studies on celecoxib and aspirin; and additional immunomodulatory therapeutic strategies.

Keywords: COX-2 inhibition; Inflammation; aspirin; major depression; psychiatry; psychoneuroimmunology; schizophrenia.

Figure 1

Vulnerability–stress–inflammation hypothesis of schizophrenia. LPS, lipopolysaccharides; poly:IC, polyinosinic–polycytidylic acid.