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Open Access Highly Accessed Opinion

Aspirin: a review of its neurobiological properties and therapeutic potential for mental illness

Michael Berk1234*, Olivia Dean124, Hemmo Drexhage5, John J McNeil6, Steven Moylan1, Adrienne O'Neil16, Christopher G Davey3, Livia Sanna1 and Michael Maes17

Author Affiliations

1 School of Medicine, Deakin University, 75 Pigdon's Road, Waurn Ponds, Geelong, Victoria, 3216, Australia

2 Department of Psychiatry, University of Melbourne, Parkville, Victoria, 3052, Australia

3 Orygen Youth Health Research Centre, 35 Poplar Road, Parkville, Victoria, 3052, Australia

4 Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, 3052, Australia

5 Department of Immunology, Erasmus Medical Center, 3015 CE Rotterdam, The Netherlands

6 School of Public Health and Preventive Medicine, Monash University, Melbourne

7 Maes Clinics @ TRIA, Bangkok, Thailand

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BMC Medicine 2013, 11:74  doi:10.1186/1741-7015-11-74

Published: 18 March 2013

Abstract

There is compelling evidence to support an aetiological role for inflammation, oxidative and nitrosative stress (O&NS), and mitochondrial dysfunction in the pathophysiology of major neuropsychiatric disorders, including depression, schizophrenia, bipolar disorder, and Alzheimer's disease (AD). These may represent new pathways for therapy. Aspirin is a non-steroidal anti-inflammatory drug that is an irreversible inhibitor of both cyclooxygenase (COX)-1 and COX-2, It stimulates endogenous production of anti-inflammatory regulatory 'braking signals', including lipoxins, which dampen the inflammatory response and reduce levels of inflammatory biomarkers, including C-reactive protein, tumor necrosis factor-α and interleukin (IL)--6, but not negative immunoregulatory cytokines, such as IL-4 and IL-10. Aspirin can reduce oxidative stress and protect against oxidative damage. Early evidence suggests there are beneficial effects of aspirin in preclinical and clinical studies in mood disorders and schizophrenia, and epidemiological data suggests that high-dose aspirin is associated with a reduced risk of AD. Aspirin, one of the oldest agents in medicine, is a potential new therapy for a range of neuropsychiatric disorders, and may provide proof-of-principle support for the role of inflammation and O&NS in the pathophysiology of this diverse group of disorders.

Keywords:
aspirin; depression; schizophrenia; dementia; inflammation; cytokines; neuroprogression; treatment; COX