Alternative Complement Pathway in Schizophrenia

Abstract

In the present study, we evaluated functional activity of the alternative pathway of complement in schizophrenia by measuring the alternative pathway hemolytic activity (AH50) of complement as well as hemolytic activity of the complement C3 component (C3H50) in the blood of patients with schizophrenia and healthy subjects. To assess the influence of neuroleptic treatment on measured parameters, both drug-free and medicated patients were examined. In addition, correlation analysis between AH50 and C3H50 has been performed. The results of the present study clearly demonstrate upregulation of the alternative complement cascade in schizophrenia and activator effect of neuroleptics on complement alternative pathway. Based upon the results obtained we hypothesize that hyperactivation of the alternative complement pathway in schizophrenia is stimulated by apoptotic cells.

Complement: a key system for immune surveillance and homeostasis

“…4b)142,151, the same process can be triggered by reactive astrocytes in the damaged or diseased brain, thereby contributing to the pathogenesis of neurological and neurodegenerative diseases. Indeed, complement has been linked not only to AD (see above) but also to glaucoma152, Parkinson's disease153, multiple sclerosis154, and schizophrenia155,156. Conversely, impaired complement activity early in development may be detrimental, given the surprising role for C3a-C3aR signaling in the control of neural crest migration during early embryogenesis157.…”

Functional variants of the genes involved in neurodevelopment and susceptibility to schizophrenia in an Armenian population

“…Several studies, including our own, suggest the implication of both the neuronal development and the immune system abnormalities in the etiology of schizophrenia, a complex disease with substantial genetic background [1][2][3][4][5]. Accordingly, the genes encoding proteins participating in neuronal growth, differentiation, synapse formation, neurotransmission immune mediation, and regulation are considered important candidate susceptibility genes for schizophrenia [6,7].…”

Functional characterization of the complement receptor type 1 and its circulating ligands in patients with schizophrenia

“…Alterations in functional activities of classical, alternative and lectin pathways of complement, a major mediator of the immune response, as well as changes in blood levels and expression profiles of its C1q, C3, and C4 components have been detected in schizophrenia-affected subjects [18-22]. However, little is known about receptors and regulators of the complement system in schizophrenia.…”