Associations Between Non-neurological Autoimmune Disorders and Psychosis: A Meta-analysis

Cullen, Alexis E.; Holmes, Scarlett; Pollak, Thomas A; Blackman, Graham; Joyce, Daniel; Kempton, Matthew J.; Murray, Robin M.; McGuire, Philip; Mondelli, Valeria

doi:10.1016/j.biopsych.2018.06.016

Cited by 102 publications

(81 citation statements)

References 81 publications

(139 reference statements)

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“…For example, epidemiological studies have reported an association between maternal infection during pregnancy and increased risk for schizophrenia. Also, a meta‐analysis showed an association between schizophrenia and autoimmune disorders. Recent evidence from genetic studies indicates that schizophrenia‐related loci include several genes involved in the immune system.…”

Section: Recent Developments and Future Directions For Research On Comentioning

confidence: 99%

Nonsocial and social cognition in schizophrenia: current evidence and future directions

2019

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Cognitive impairment in schizophrenia involves a broad array of nonsocial and social cognitive domains. It is a core feature of the illness, and one with substantial implications for treatment and prognosis. Our understanding of the causes, consequences and interventions for cognitive impairment in schizophrenia has grown substantially in recent years. Here we review a range of topics, including: a) the types of nonsocial cognitive, social cognitive, and perceptual deficits in schizophrenia; b) how deficits in schizophrenia are similar or different from those in other disorders; c) cognitive impairments in the prodromal period and over the lifespan in schizophrenia; d) neuroimaging of the neural substrates of nonsocial and social cognition, and e) relationships of nonsocial and social cognition to functional outcome. The paper also reviews the considerable efforts that have been directed to improve cognitive impairments in schizophrenia through novel psychopharmacology, cognitive remediation, social cognitive training, and alternative approaches. In the final section, we consider areas that are emerging and have the potential to provide future insights, including the interface of motivation and cognition, the influence of childhood adversity, metacognition, the role of neuroinflammation, computational modelling, the application of remote digital technology, and novel methods to evaluate brain network organization. The study of cognitive impairment has provided a way to approach, examine and comprehend a wide range of features of schizophrenia, and it may ultimately affect how we define and diagnose this complex disorder.

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Section: Recent Developments and Future Directions For Research On Comentioning

confidence: 99%

Nonsocial and social cognition in schizophrenia: current evidence and future directions

2019

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“…(156)]. Recent meta-analysis suggests a positive association between nonneurological autoimmune disorders and psychosis (157). The risk for developing schizophrenia in people with autoimmune disorders was found to increase in association with increasing number of hospitalisations for infections (158), suggesting a synergistic effect.…”

Section: Influenza and Autoimmunitymentioning

confidence: 99%

Schizophrenia and Influenza at the Centenary of the 1918-1919 Spanish Influenza Pandemic: Mechanisms of Psychosis Risk

et al. 2020

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Associations between influenza infection and psychosis have been reported since the eighteenth century, with acute "psychoses of influenza" documented during multiple pandemics. In the late 20 th century, reports of a season-of-birth effect in schizophrenia were supported by large-scale ecological and sero-epidemiological studies suggesting that maternal influenza infection increases the risk of psychosis in offspring. We examine the evidence for the association between influenza infection and schizophrenia risk, before reviewing possible mechanisms via which this risk may be conferred. Maternal immune activation models implicate placental dysfunction, disruption of cytokine networks, and subsequent microglial activation as potentially important pathogenic processes. More recent neuroimmunological advances focusing on neuronal autoimmunity following infection provide the basis for a model of infection-induced psychosis, potentially implicating autoimmunity to schizophrenia-relevant protein targets including the Nmethyl-D-aspartate receptor. Finally, we outline areas for future research and relevant experimental approaches and consider whether the current evidence provides a basis for the rational development of strategies to prevent schizophrenia.

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“…Studies have also shown that individuals with mental disorders such as schizophrenia (6,7) and depression (3,4,8) have a subsequently increased risk of autoimmune diseases. Furthermore, this association between autoimmune diseases and mental disorders has been confirmed in a recent meta-analysis (9).…”

Section: Introductionmentioning

confidence: 68%

“…However, not all autoimmune diseases are associated with mental disorders (9), and there is a welldocumented negative association between rheumatoid arthritis and schizophrenia (10).…”

Section: Introductionmentioning

confidence: 99%

Genetic factors underlying the bidirectional relationship between autoimmune and mental disorders – findings from a Danish population-based study

Liu

Thompson

Appadurai

et al. 2019

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Background:Previous studies have indicated the bidirectionality between autoimmune and mental disorders.However, genetic studies underpinning the co-occurrence of the two disorders have been lacking. In this study, we examined the potential genetic contribution to the association between autoimmune and mental disorders. Methods:We used diagnostic information for patients with seven autoimmune diseases and six mental disorders from the Danish population-based case-cohort sample (iPSYCH2012). We explored the epidemiological association using survival analysis and modelled the effect of polygenic risk scores (PRSs) on two diseases. The genetic factors were investigated using GWAS and HLA imputation data based on iPSYCH cohort. Results:Among 64,039 individuals, a total of 43,902 (68.6%) were diagnosed with mental disorders and 1,383 (2.2%) with autoimmune diseases. There was a significant comorbidity between the two diseases (P=2.67×10 -7 , OR=1.38, 95%CI=1.22-1.56), with an overall bidirectional association wherein individuals with autoimmune diseases had an increased risk of subsequent mental disorders (HR=1.13, 95%CI: 1.07-1.21, P=7.95×10 -5 ) and vice versa (HR=1.27, 95%CI=1.16-1.39, P=8.77×10 -15 ). Though PRSs were significantly correlated with both types of diagnosis, PRSs had little effect on the bidirectional relationship. Importantly, we for the first time observed 12 human leukocyte antigen (HLA) loci and 20 HLA alleles strongly associated with overall autoimmune diseases, but we did not find significant evidence of their associations with overall mental disorders. 4 Conclusions:Our findings confirm the overall comorbidity and bidirectionality between autoimmune and mental disorders and discover HLA genes which are significantly associated with overall autoimmune diseases, but not with overall mental disorders. ≤ 0.05) were followed up with allele-specific tests for the relevant phenotype-gene associations. Statistical analysisThe chi-squared test was applied to examine the epidemiological correlation between autoimmune and mental disorders. Odds ratio (OR) and 95% confidence intervals (95%CI) were calculated using the "epitools" package in R (23).

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Associations Between Non-neurological Autoimmune Disorders and Psychosis: A Meta-analysis

Cited by 102 publications

References 81 publications

Nonsocial and social cognition in schizophrenia: current evidence and future directions

Nonsocial and social cognition in schizophrenia: current evidence and future directions

Schizophrenia and Influenza at the Centenary of the 1918-1919 Spanish Influenza Pandemic: Mechanisms of Psychosis Risk

Genetic factors underlying the bidirectional relationship between autoimmune and mental disorders – findings from a Danish population-based study

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