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

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.

Schizophrenia and cytokines

“…[17]. Poznato je da u shizofreniji postoji dopaminergičko-glutamatergička disfunkcija, čija je neuroanatomska osnova kortiko-strijato-talamusno-kortikalni krug [18].…”

Curcumin for the treatment of major depression: A randomised, double-blind, placebo controlled study

“…Consequently, this has sparked interest in compounds that target these pathways. Examples include anti-inflammatory treatments influencing immuno-inflammation such as cyclooxygensase-2 (COX-2) inhibitors, aspirin, minocycline and polyunsaturated fatty acids (Berk et al, 2013a, Fond et al, 2014, Muller, 2013 and antioxidant therapies to increase antioxidant defences and lower free radical damage such as n-acetyl cysteine, Ebselen, vitamin E and coenzyme-Q 10 (Berk et al, 2013b, Scapagnini et al, 2012. Interestingly, despite pharmaceutical antidepressants originally being heralded as targeting monoaminergic actions, there is also evidence that they can modulate immuno-inflammation, reduce oxidative stress, enhance neurotrophic factors and influence HPA activity (Abdel-Wahab and Salama, 2011, Andrade and Rao, 2010, Hannestad et al, 2011, Kocki et al, 2012, Schule, 2007.…”

The Integrative Management of Treatment-Resistant Depression: A Comprehensive Review and Perspectives

“…ketamine) [24,25] as well as scopolamine (an anticholinergic agent) [26] have been tested with encouraging results in recent RCT. In addition, inflammatory and oxidative pathways are showing promise as novel treatment targets [27], with agents as diverse as pioglitazone [28], minocycline [29], celecoxib [28], N-acetylcysteine [28] and aspirin [30] showing evidence of utility.…”