Schizophrenia: Complement Cleaning or Killing
Open Access
- 11 February 2021
- Vol. 12 (2), 259
- https://doi.org/10.3390/genes12020259
Abstract
Schizophrenia is a psychiatric disorder with a typical onset occurring during adolescence or young adulthood. The heterogeneity of the disorder complicates our understanding of the pathophysiology. Reduced cortical synaptic densities are commonly observed in schizophrenia and suggest a role for excessive synaptic elimination. A major pathway hypothesised to eliminate synapses during postnatal development is the complement system. This review provides an overview of genetic and functional evidence found for the individual players of the classical complement pathway. In addition, the consequences of the absence of complement proteins, in the form of complement protein deficiencies in humans, are taken into consideration. The collective data provide strong evidence for excessive pruning by the classical complement pathway, contributing to cognitive impairment in schizophrenia. In future studies, it will be important to assess the magnitude of the contribution of complement overactivity to the occurrence and prevalence of phenotypic features in schizophrenia. In addition, more insight is required for the exact mechanisms by which the complement system causes excessive pruning, such as the suggested involvement of microglial engulfment and degradation of synapses. Ultimately, this knowledge is a prerequisite for the development of therapeutic interventions for selective groups of schizophrenia patients.This publication has 74 references indexed in Scilit:
- Childhood infection and adult schizophrenia: A meta-analysis of population-based studiesSchizophrenia Research, 2012
- New developments in C5a receptor signalingCell Health and Cytoskeleton, 2012
- Taming lupus—a new understanding of pathogenesis is leading to clinical advancesNature Medicine, 2012
- Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent MannerNeuron, 2012
- Spike timing plays a key role in synapse elimination at the neuromuscular junctionProceedings of the National Academy of Sciences of the United States of America, 2012
- Genome-wide association study identifies five new schizophrenia lociNature Genetics, 2011
- Extraordinary neoteny of synaptic spines in the human prefrontal cortexProceedings of the National Academy of Sciences of the United States of America, 2011
- Enhanced synaptic connectivity and epilepsy in C1q knockout miceProceedings of the National Academy of Sciences of the United States of America, 2010
- MEGF10 Association with SchizophreniaBiological Psychiatry, 2008
- DEVELOPMENT OF THE VERTEBRATE NEUROMUSCULAR JUNCTIONAnnual Review of Neuroscience, 1999