Assessing whether the association between rheumatoid arthritis and schizophrenia is bidirectional: A nationwide population-based cohort study

Abstract

Since many studies have shown a reduction in the incidence of rheumatoid arthritis (RA) in patients with schizophrenia (SCZ), little effort has been devoted to studying this link in the Asian population. Moreover, the relationship between these two disorders could be bidirectional, but the influence of RA on the SCZ incidence is unclear. The study aims to determine whether there is a bidirectional association between RA and SCZ in an Asian population. We analyzed a 10-year population- based longitudinal cohort using the National Health Insurance Research Database of Taiwan. In the first analysis, we included a total of 58,847 SCZ patients and 235,382 non-SCZ controls, and in the second analysis, a total of 30,487 RA patients and 121,833 non-RA controls, both matched by gender, age, and index date. Cox regression analyses were performed to examine the risk of RA incidence in the first analysis and the risk of SCZ incidence in the second analysis. The main finding of this study was the discovery of a lower incidence of RA in patients with SCZ (hazard ratio (HR): 0.48, 95% confidence interval (95% CI): 0.31–0.77) after adjustment for baseline demographics and comorbidities. Additionally, the presence of RA predicted a reduced incidence rate for SCZ, but the estimate was not statistically significant (HR: 0.77, 95% CI: 0.44–1.37). The study found a unidirectional association between RA and SCZ. However, RA has an age of onset later than RA, and the protective effect of RA on SCZ incidence would be biased due to the limited number of cases.

Meta-Analysis of Transcriptomic Data of Dorsolateral Prefrontal Cortex and of Peripheral Blood Mononuclear Cells Identifies Altered Pathways in Schizophrenia

“…Chen et al reported a lower incidence of RA in patients with SCZ after adjustment for demographics and comorbidities [81]. Moreover, the presence of RA predicted a reduced, although not significant, incidence rate for SCZ [81]. This is also in line with the observation of a negative correlation between gene expression patterns in SCZ and RA [82], as well as with the small but significant negative SNP-genetic correlation between these diseases [83].…”

“…It is worth noting that the alteration of the MAPK signaling pathway in SCZ may partly explain the negative correlation between SCZ and rheumatoid arthritis (RA), as a large body of data points to the pathogenetic role of MAPK signaling in RA [77][78][79][80]. Chen et al reported a lower incidence of RA in patients with SCZ after adjustment for demographics and comorbidities [81]. Moreover, the presence of RA predicted a reduced, although not significant, incidence rate for SCZ [81].…”

Assessment of Subclinical Psychotic Symptoms in Patients with Rheumatoid Arthritis and Spondyloarthritis

“…However, to date, no publications have reflected a greater prevalence of psychotic episodes for either of these diseases. In fact, in the case of RA, an inverse association has been reported between RA and the most representative manifestation of psychosis, namely, schizophrenia [30][31][32][33]. Similarly, a recent study reported this same negative association not only for RA, but also for SpA [19].…”

Immunoceptive inference: why are psychiatric disorders and immune responses intertwined?

“…A number of central symptoms of psychiatric disorders can also be understood as hypersensitivities-such as social threat hypersensitivity in borderline personality disorder and depression (Bertsch et al 2013;Slavich and Irwin 2014;Badcock et al 2017) or sensory hypersensitivities in autism (Takarae et al 2016). There are several well-established links between hypersensitivities and psychiatric disorders; for example, systemic lupus erythematosus (SLE) and depression (Moustafa et al 2020); thyroiditis and anxiety (Siegmann et al 2018); maternal diabetes type 1 and autism (Xiang et al 2018); SLE, psoriasis, rheumatoid arthritis and schizophrenia (Tiosano et al 2017;Chen et al 2019;Ungprasert et al 2019). Indeed, some accounts even suggest that schizophrenia is an autoimmune disorder (Knight et al 1992;Adams et al 2012).…”