Anti-Inflammatory Therapy as a Promising Target in Neuropsychiatric Disorders

Abstract

This chapter analyzes the therapeutic potential of current anti-inflammatory drugs in treating psychiatric diseases from a neuro-immunological perspective. Based on the bidirectional brain-immune system relationship, the rationale is that a dysregulated inflammation contributes to the pathogenesis of psychiatric and neurological disorders, while the immunology function is associated with psychological variables like stress, affective disorders, and psychosis. Under certain social, psychological, and environmental conditions and biological factors, a healthy inflammatory response and the associated "sickness behavior," which are aimed to resolve a physical injury and microbial threat, become harmful to the central nervous system. The features and mechanisms of the inflammatory response are described across the main mental illnesses with a special emphasis on the profile of cytokines and the function of the HPA axis. Next, it is reviewed the potential clinical utility of immunotherapy (cytokine agonists and antagonists), glucocorticoids, unconventional anti-inflammatory agents (statins, minocycline, statins, and polyunsaturated fatty acids (PUFAs)), the nonsteroidal anti-inflammatory drugs (NSAIDs), and particularly celecoxib, a selective cyclooxygenase-2 (Cox-2) inhibitor, as adjuvants of conventional psychiatric medications. The implementation of anti-inflammatory therapies holds great promise in psychiatry. Because the inflammatory background may account for the etiology and/or progression of psychiatric disorders only in a subset of patients, there is a need to elucidate the immune underpinnings of the mental illness progression, relapse, and remission. The identification of immune-related bio-signatures will ideally assist in the stratification of the psychiatric patient to predict the risk of mental disease, the prognosis, and the response to anti-inflammatory therapy.

Keywords: Anti-inflammatory agents; Cytokines; Glucocorticoids; Inflammation; Mental disorders; Psychoneuroimmunology.