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.
Highlights
Treatment options for common neuropsychiatric disorders, including depression, schizophrenia, and bipolar disorder, have focused on medications that modify the activity of monoamine neurotransmitter systems
Other reviews that have explored the use of somatic drugs for psychiatric diseases have placed a strong focus on COX-2 as the most important and powerful anti-inflammatory [12], but in this paper, we propose that COX-1 is the key component in neurodegeneration and neuroinflammation, and a potential target for therapeutic intervention [12]
The authors found that oral aspirin may increase the production of cytokine-induced, but not lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-a and IL-1b production, suggesting that short-term treatment with aspirin might augment cytokine-induced cytokine production in normal controls. These results provide some evidence that administration of aspirin to patients with inflammatory conditions may suppress the production of TNF-a, IL-1b and maybe IL-6, and of acute-phase proteins such as C-reactive protein (CRP)
Summary
Treatment options for common neuropsychiatric disorders, including depression, schizophrenia, and bipolar disorder, have focused on medications that modify the activity of monoamine neurotransmitter systems. The aforementioned Danish national study [64] confirmed these findings by showing an association of bipolar disorder with a family history of pernicious anemia, and with presence of Guillain-Barré syndrome, inflammatory bowel disease, and autoimmune hepatitis in individual patients These findings imply shared immune pathogenic factors for mood disorders, schizophrenia, and organ-specific autoimmune diseases. In order to understand the clinical efficacy of aspirin in neuropsychiatric disorders such as depression and schizophrenia, it is more important to consider how its inhibition of COX-1 affects the five aforementioned pathways This is supported by data suggesting lower response rates to antidepressants in people receiving NSAIDs [104], but is at odds with some recent studies suggesting a benefit for celecoxib, a COX2 inhibitor, in several disorders including autism and depression [105,106].
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