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

Abstract

Background: A relationship between non-neurological autoimmune (NNAI) disorders and psychosis has been widely reported but not yet subjected to meta-analysis. We conducted the first meta-analysis examining the association between NNAI disorders and psychosis and investigated the effect of 1) temporality (as determined by study design), 2) psychiatric diagnosis, and 3) specific autoimmune disorders.

Methods: Major databases were searched for articles published until April 2018; 31 studies, comprising data for >25 million individuals, were eligible. Using random-effects models, we examined the overall association between all NNAI disorders and psychosis; rheumatoid arthritis was examined separately given the well-established negative association with psychosis. Stratified analyses investigated the effect of temporality, psychiatric diagnosis, and specific NNAI disorders.

Results: We observed a positive overall association between NNAI disorders and psychosis (odds ratio [OR] = 1.26; 95% confidence interval [CI], 1.12-1.41) that was consistent across study designs and psychiatric diagnoses; however, considerable heterogeneity was detected (I² = 88.08). Patterns varied across individual NNAI disorders; associations were positive for pernicious anemia (OR = 1.91; 95% CI, 1.29-2.84), pemphigoid (OR = 1.90; 95% CI, 1.62-2.24), psoriasis (OR = 1.70; 95% CI, 1.51-1.91), celiac disease (OR = 1.53; 95% CI, 1.12-2.10), and Graves' disease (OR = 1.33; 95% CI, 1.03-1.72) and negative for ankylosing spondylitis (OR = 0.72; 95% CI, 0.54-0.98) and rheumatoid arthritis (OR = 0.65; 95% CI, 0.50-0.84).

Conclusions: While we observed a positive overall association between NNAI disorders and psychosis, this was not consistent across all NNAI disorders. Specific factors, including distinct inflammatory pathways, genetic influences, autoantibodies targeting brain proteins, and exposure to corticosteroid treatment, may therefore underlie this association.

Keywords: Autoimmune; Epidemiology; Inflammation; Meta-analysis; Psychosis; Schizophrenia.

Figure 1

Search process. Overview of the review process and reasons for exclusion.

Figure 2

Results of overall meta-analysis for all non-neurological autoimmune disorders (except rheumatoid arthritis) and psychosis. Marker and line colors indicate study design: type A (red), type B (blue), type C (pink). AI, autoimmune; CI, confidence interval; Diag, psychiatric diagnosis; HSV, hypersensitivity vasculitis; NSP, nonschizophrenia psychosis; OR, odds ratio; PY, psychosis; SLE, systemic lupus erythematosus; SZ, schizophrenia. ^aAutoimmune hemolytic type. ^bHereditary hemolytic type. ^cPernicious type. ^dAcquired hemolytic. ^eOther hereditary hemolytic type. ^fChildhood-onset.

Figure 3

Results of meta-analysis for rheumatoid arthritis and psychosis. All studies examine schizophrenia with the following exceptions: Allebeck et al. (1985; second row) , nonschizophrenia psychosis; Sundquist et al. (2008; first row) , nonschizophrenia psychosis; Rothermich and Philips (1963) , broadly defined psychosis. Specific rheumatoid arthritis subtypes are as follows: Chen et al. (2012; second row) , juvenile-onset; Eaton et al. (2006; second row) , seropositive; Mors et al. (1999; second row) , juvenile-onset. Marker and line colors indicate study design: type A (red), type B (blue), type C (pink). CI, confidence interval; OR, odds ratio.