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The complement system in schizophrenia: where are we now and what's next?
Julia J Woo1, Jennie G Pouget1, Clement C Zai1
1Tanenbaum Centre for Pharmacogenetics, Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health, 250 College Street, Toronto, ON, M5T 1R8, Canada.
Molecular Psychiatry
|August 24, 2019
Summary
The complement system, particularly complement component 4 (C4) and CSMD1, shows elevated activity in schizophrenia. These complement factors are potential new drug targets for treating schizophrenia.
Area of Science:
- Neuroimmunology
- Genetics
- Psychiatry
Background:
- The complement system is crucial for innate immunity and waste clearance.
- Emerging evidence links complement cascade dysregulation to central nervous system disorders like schizophrenia.
- Previous reviews highlighted the need for updated research on complement and schizophrenia.
Purpose of the Study:
- To provide a narrative review and critique of current literature on the relationship between schizophrenia and the complement system.
- To identify potential genetic markers and therapeutic targets within the complement pathway for schizophrenia.
Main Methods:
- Comprehensive literature search for studies published since 2008.
- Analysis of complement gene polymorphisms, gene expression, protein concentrations, and pathway activity.
- Gene and gene-set analysis using MAGMA to assess genetic associations.
Main Results:
- Overall complement pathway activity appears elevated in schizophrenia.
- Complement component 4 (C4) and CSMD1 are identified as potential genetic markers.
- Evidence suggests C4 gene variants and altered C4 expression in schizophrenia patients.
Conclusions:
- Complement components, especially C4 and CSMD1, are implicated in schizophrenia pathogenesis.
- These complement factors represent promising novel drug targets for schizophrenia treatment.
- Future clinical trials are needed to evaluate complement-targeted therapies for schizophrenia.