Autoimmune Diseases and Severe Infections as Risk Factors for Schizophrenia: A 30-Year Population-Based Register Study
Abstract
Objective:
Method:
Results:
Conclusions:
Method
Registers
Study Population
Assessment of Schizophrenia and Other Mental Illness
Assessment of Autoimmune Disease and Infection
Schizophrenia Spectrum Disorders in Persons Without Infections | Schizophrenia Spectrum Disorders in Persons With Infections | |||||
---|---|---|---|---|---|---|
Autoimmune Disease | Incidence Rate Ratiob | 95% CI | Case Patients | Incidence Rate Ratiob | 95% CI | Case Patients |
Persons without autoimmune disease (reference) | 1.00 | Reference | 29,372 | 1.60 | 1.56–1.64 | 8,777 |
Any autoimmune disease | 1.29 | 1.18–1.41 | 483c | 2.25 | 2.04–2.46 | 444c |
Autoimmune disease with suspected presence of brain reactive antibodies | 1.48 | 1.31–1.68 | 244 | 2.56 | 2.25–2.89 | 243 |
Autoimmune hepatitis | 2.75 | 1.38–4.83 | 10 | 8.91 | 6.50–11.84 | 43 |
Autoimmune thyroiditis | 3 | 4.57 | 2.09–8.51 | 8 | ||
Celiac disease | 2.11 | 1.09–3.61 | 11 | 2.47 | 1.13–4.61 | 8 |
Guillain-Barré syndrome | 1.22 | 0.58–2.19 | 9 | 2.84 | 1.52–4.76 | 12 |
Multiple sclerosis | 1.44 | 1.03–1.94 | 39 | 2.10 | 1.37–3.06 | 24 |
Sjögren's syndrome | 2.07 | 0.82–4.20 | 6 | 4 | ||
Systemic lupus erythematosus | 1.84 | 0.92–3.23 | 10 | 2.11 | 1.06–3.70 | 10 |
Thyrotoxicosis (Graves' disease) | 1.94 | 1.47–2.49 | 56 | 2.47 | 1.68–3.49 | 29 |
Type I diabetes | 1.27 | 1.04–1.53 | 104 | 2.04 | 1.68–2.44 | 109 |
Other autoimmune diseases | 1.19 | 1.05–1.34 | 256 | 1.95 | 1.70–2.23 | 212 |
Ankylosing spondylitis | 1.38 | 0.79–2.20 | 15 | 1.68 | 0.72–3.25 | 7 |
Crohn's disease | 1.22 | 0.88–1.65 | 39 | 1.67 | 1.18–2.27 | 36 |
Iridocyclitis | 1.32 | 0.87–1.91 | 25 | 1.99 | 1.21–3.06 | 18 |
Juvenile arthritis | 1.00 | 0.52–1.71 | 11 | 1.77 | 0.95–2.97 | 12 |
Psoriasis vulgaris | 1.37 | 1.01–1.80 | 47 | 2.77 | 2.07–3.63 | 49 |
Seropositive rheumatoid arthritis | 0.75 | 0.51–1.06 | 28 | 2.15 | 1.52–2.95 | 35 |
Ulcerative colitis | 1.22 | 0.97–1.51 | 80 | 1.65 | 1.24–2.14 | 52 |
Autoimmune diseases with too few cases to calculate individual riskd | 1.59 | 1.13–2.17 | 36 | 2.21 | 1.53–3.07 | 32 |
Data Analyses
Results
General Population | No Substance Abuse | No Psychiatric Family Historyb | Psychiatric Family Historyb | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Autoimmune Disease and Infection | Incidence Rate Ratioc | 95% CI | Case Patients | Incidence Rate Ratioc | 95% CI | Case Patients | Incidence Rate Ratioc | 95% CI | Case Patients | Incidence Rate Ratioc | 95% CI | Case Patients |
Persons without a hospital contact for an autoimmune disease or infection (reference) | 1.00 | Reference | 29,372 | 1.00 | Reference | 22,730 | 1.00 | Reference | 16,041 | 1.00 | Reference | 5,515 |
Autoimmune disease | 1.30 | 1.19–1.42 | 483 | 1.29 | 1.16–1.43 | 353 | 1.26 | 1.11–1.43 | 238 | 1.16 | 0.93–1.44 | 83 |
One infection | 1.39 | 1.35–1.43 | 5,121 | 1.27 | 1.22–1.31 | 3,600 | 1.32 | 1.27–1.37 | 2,908 | 1.23 | 1.15–1.31 | 1,242 |
One infection and autoimmune disease | 1.73 | 1.48–2.00 | 177 | 1.52 | 1.26–1.82 | 114 | 1.66 | 1.34–2.03 | 91 | 1.27 | 0.88–1.76 | 32 |
Two infections | 1.70 | 1.62–1.78 | 1,789 | 1.46 | 1.37–1.54 | 1,171 | 1.59 | 1.49–1.69 | 1,007 | 1.41 | 1.28–1.55 | 470 |
Two infections and autoimmune disease | 2.21 | 1.79–2.68 | 96 | 2.11 | 1.64–2.66 | 66 | 2.26 | 1.70–2.92 | 53 | 1.26 | 0.73–2.02 | 15 |
Three or more infections | 2.56 | 2.44–2.69 | 1,867 | 1.99 | 1.87–2.11 | 1,070 | 2.33 | 2.18–2.49 | 997 | 1.94 | 1.77–2.12 | 554 |
Three or more infections and autoimmune disease | 3.40 | 2.91–3.94 | 171 | 2.58 | 2.08–3.15 | 89 | 3.17 | 2.54–3.89 | 86 | 2.79 | 2.03–3.71 | 43 |
Total | 39,076 | 29,193 | 21,421 | 7,954 |
Infection Only (No Autoimmune Disease) | Autoimmune Disease | |||||
---|---|---|---|---|---|---|
Infection | Incidence Rate Ratiob | 95% CI | Case Patients | Incidence Rate Ratiob | 95% CI | Case Patients |
Sepsis | 1.95 | 1.47–2.51 | 55 | 4.98 | 2.49–8.73 | 10 |
Hepatitis | 4.89 | 4.26–5.58 | 212 | 8.89 | 6.03–12.53 | 29 |
Gastrointestinal | 1.32 | 1.26–1.39 | 1,847 | 1.82 | 1.46–2.24 | 83 |
Skin | 1.71 | 1.62–1.80 | 1,427 | 2.14 | 1.69–2.66 | 74 |
Pregnancy-related | 1.14 | 0.98–1.31 | 185 | 1.22 | 0.48–2.47 | 6 |
Respiratory | 1.53 | 1.46–1.61 | 1,885 | 2.25 | 1.79–2.79 | 77 |
Urogenital | 1.90 | 1.79–2.01 | 1,200 | 2.70 | 2.10–3.41 | 66 |
CNS | 1.28 | 1.09–1.50 | 148 | 2.62 | 1.31–4.60 | 10 |
Other | 1.70 | 1.62–1.78 | 1,818 | 1.99 | 1.60–2.43 | 89 |
Persons without hospital contact for infection (reference) | 1.00 | 29,372 | 1.30 | 1.18–1.42 | 483 |
Infection Only (No Autoimmune Disease) | Autoimmune Disease | |||||
---|---|---|---|---|---|---|
Time Since Last Severe Infection | Incidence Rate Ratiob | 95% CI | Case Patients | Incidence Rate Ratiob | 95% CI | Case Patients |
<1 year | 2.35 | 2.20–2.51 | 901 | 2.91 | 2.18–3.80 | 50 |
1 year | 1.89 | 1.75–2.04 | 670 | 2.85 | 2.09–3.77 | 44 |
2 years | 1.73 | 1.59–1.87 | 576 | 2.46 | 1.73–3.37 | 35 |
3–4 years | 1.66 | 1.56–1.77 | 1,020 | 2.42 | 1.86–3.08 | 61 |
5–9 years | 1.51 | 1.44–1.58 | 1,931 | 2.10 | 1.72–2.54 | 100 |
10–14 years | 1.46 | 1.38–1.53 | 1,524 | 2.31 | 1.83–2.87 | 76 |
≥15 years | 1.42 | 1.35–1.48 | 2,155 | 1.68 | 1.33–2.08 | 78 |
Persons without hospital contact for infection (reference) | 1.00 | 29,372 | 1.29 | 1.18–1.41 | 483 |
Discussion
Strengths and Limitations
Footnotes
References
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