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The complement system in schizophrenia: where are we now and what's next?
Woo, Julia J; Pouget, Jennie G; Zai, Clement C; Kennedy, James L.
Afiliação
  • Woo JJ; Tanenbaum Centre for Pharmacogenetics, Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health, 250 College Street, Toronto, ON, M5T 1R8, Canada.
  • Pouget JG; Tanenbaum Centre for Pharmacogenetics, Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health, 250 College Street, Toronto, ON, M5T 1R8, Canada.
  • Zai CC; Tanenbaum Centre for Pharmacogenetics, Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health, 250 College Street, Toronto, ON, M5T 1R8, Canada.
  • Kennedy JL; Tanenbaum Centre for Pharmacogenetics, Campbell Family Mental Health Research Institute, Center for Addiction and Mental Health, 250 College Street, Toronto, ON, M5T 1R8, Canada. Jim.Kennedy@camh.ca.
Mol Psychiatry ; 25(1): 114-130, 2020 01.
Article em En | MEDLINE | ID: mdl-31439935
ABSTRACT
The complement system is a set of immune proteins involved in first-line defense against pathogens and removal of waste materials. Recent evidence has implicated the complement cascade in diseases involving the central nervous system, including schizophrenia. Here, we provide an up-to-date narrative review and critique of the literature on the relationship between schizophrenia and complement gene polymorphisms, gene expression, protein concentration, and pathway activity. A literature search identified 23 new studies since the first review on this topic in 2008. Overall complement pathway activity appears to be elevated in schizophrenia. Recent studies have identified complement component 4 (C4) and CUB and Sushi Multiple Domains 1 (CSMD1) as potential genetic markers of schizophrenia. In particular, there is some evidence of higher rates of C4B/C4S deficiency, reduced peripheral C4B concentration, and elevated brain C4A mRNA expression in schizophrenia patients compared to controls. To better elucidate the additive effects of multiple complement genotypes, we also conducted gene- and gene-set analysis through MAGMA which supported the role of Human Leukocyte Antigen class (HLA) III genes and, to a lesser extent, CSMD1 in schizophrenia; however, the HLA-schizophrenia association was likely driven by the C4 gene. Lastly, we identified several limitations of the literature on the complement system and schizophrenia, including small sample sizes, inconsistent methodologies, limited measurements of neural concentrations of complement proteins, little exploration of the link between complement and schizophrenia phenotype, and lack of studies exploring schizophrenia treatment response. Overall, recent findings highlight complement components-in particular, C4 and CSMD1-as potential novel drug targets in schizophrenia. Given the growing availability of complement-targeted therapies, future clinical studies evaluating their efficacy in schizophrenia hold the potential to accelerate treatment advances.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Esquizofrenia / Proteínas do Sistema Complemento Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Mol Psychiatry Assunto da revista: BIOLOGIA MOLECULAR / PSIQUIATRIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Canadá

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Esquizofrenia / Proteínas do Sistema Complemento Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Mol Psychiatry Assunto da revista: BIOLOGIA MOLECULAR / PSIQUIATRIA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Canadá