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Familial Mediterranean fever association with schizophrenia: insights from big data analysis
Kassem Sharif1,2,3, Abdulla Watad2,3, Nicola Luigi Bragazzi4
1University of Leeds, United Kingdom.
Introduction:
Several autoimmune diseases have been associated with schizophrenia; however, little is known about putative links with auto-inflammatory conditions. We investigated the association between familial Mediterranean fever (FMF), a paradigmatic auto-inflammatory disease, and schizophrenia and assessed the impact of the latter on the survival of FMF patients.
Material And Methods:
A case-control study was performed by utilising the database of Clalit Health Services, the largest health maintenance organisation in Israel. Familial Mediterranean fever patients were compared to age- and sex-matched controls in terms of prevalence of schizophrenia. The χ2 test was used to assess the distribution of categorical variables, while the t-test was applied for continuous variables. Analysis regarding survival was performed using Kaplan-Meier curves, log rank test, and multivariate Cox proportional-hazards method. Statistical analysis was performed using SPSS version 24.0, IBM, USA.
Results:
The study included 7747 FMF patients and 10,080 age- and sex-matched controls (case-control match 1 : 1.3). On univariate analysis, 50 FMF patients (0.6%) and 89 controls (0.9%) had schizophrenia. On multiple logistic regression model, FMF was inversely associated with schizophrenia (OR = 0.64 [95% CI: 0.43-0.90], p = 0.0173). Familial Mediterranean fever (HR = 1.43 [95% CI: 1.23-1.66]) and schizophrenia (HR = 3.97 [95% CI: 1.47-10.70]) were independently associated with all-cause mortality. However, schizophrenia as a co-morbidity in FMF subjects did not worsen their prognosis (HR = 2.17 [95% CI: 0.60-7.86]).
Conclusions:
Familial Mediterranean fever patients have a significantly lower proportion of schizophrenia than controls. The current evidence shows that auto-inflammatory conditions confer protection against schizophrenia development. Patients with either FMF or schizophrenia are at higher risk of all-cause mortality, a finding that calls for assessment of better medical management of mortality outcomes.
Insights
Familial Mediterranean fever (FMF) patients showed a lower prevalence of schizophrenia, suggesting auto-inflammatory conditions may protect against schizophrenia. Schizophrenia did not worsen FMF patient survival, though both conditions increase mortality risk.
Area of Science:
- Immunology
- Psychiatry
- Genetics
Background:
- Autoimmune diseases are linked to schizophrenia.
- The relationship between auto-inflammatory conditions and schizophrenia is not well understood.
- Familial Mediterranean fever (FMF) is a key auto-inflammatory disease.
Purpose of the Study:
- To investigate the association between FMF and schizophrenia.
- To determine if schizophrenia impacts the survival of FMF patients.
Main Methods:
- A case-control study using data from Clalit Health Services in Israel.
- Compared 7,747 FMF patients with 10,080 age- and sex-matched controls for schizophrenia prevalence.
- Utilized logistic regression, Kaplan-Meier curves, and Cox proportional-hazards models for survival analysis.
Main Results:
- FMF patients had a lower prevalence of schizophrenia (0.6%) compared to controls (0.9%) (OR = 0.64).
- Both FMF (HR = 1.43) and schizophrenia (HR = 3.97) were independently associated with increased all-cause mortality.
- Schizophrenia did not significantly worsen the prognosis of FMF patients (HR = 2.17).
Conclusions:
- Auto-inflammatory conditions, like FMF, appear to confer protection against schizophrenia development.
- Individuals with FMF or schizophrenia face a higher risk of all-cause mortality.
- Improved medical management strategies are needed for patients with FMF or schizophrenia to address mortality outcomes.
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