Increased serum levels of C3 and C4 in patients with schizophrenia compared to eutymic patients with bipolar disorder and healthy

Soria, Lisiane dos Santos; Gubert, Carolina; Ceresér, Keila Maria Mendes; Gama, Clarissa Severino; Kapczinski, Flávio

doi:10.1590/s1516-44462012000100022

Cited by 38 publications

(5 citation statements)

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“…Genetic evidence suggests that the polymorphisms of C3 were associated with risk of schizophrenia (Rudduck et al, 1985;Fañanás et al, 1992;Ni et al, 2015;Zhang et al, 2018). And patients with schizophrenia had increased C3 protein levels in peripheral blood (Santos Sória et al, 2012;Ali et al, 2017) and serum C3 concentrations were positively correlated with PANSS scores (Li et al, 2016). The C4 gene has two isoforms, C4A and C4B, located within the major histocompatibility complex (MHC) region on chromosome 6.…”

Section: Introductionmentioning

confidence: 99%

Associations Between Genotype and Peripheral Complement Proteins in First-Episode Psychosis: Evidences From C3 and C4

et al. 2021

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Schizophrenia is a common neuropsychiatric disorder with complex pathophysiology. Recent reports suggested that complement system alterations contributed to pathological synapse elimination that was associated with psychiatric symptoms in schizophrenia. Complement component 3 (C3) and complement component 4 (C4) play central roles in complement cascades. In this study, we compared peripheral C3 and C4 protein levels between first-episode psychosis (FEP) and healthy control (HC). Then we explored whether single nucleotide polymorphisms (SNPs) at C3 or C4 genes affect peripheral C3 or C4 protein levels. In total, 181 FEPs and 204 HCs were recruited after providing written informed consent. We measured serum C3 and C4 protein levels using turbidimetric inhibition immunoassay and genotyped C3 and C4 polymorphisms using the Sequenom MassArray genotyping. Our results showed that three SNPs were nominally associated with schizophrenia (rs11569562/C3: A > G, p = 0.048; rs2277983/C3: A > G, p = 0.040; rs149898426/C4: G > A, p = 0.012); one haplotype was nominally associated with schizophrenia, constructed by rs11569562–rs2277983–rs1389623 (GGG, p = 0.048); FEP had higher serum C3 and C4 (both p < 0.001) levels than HC; rs1389623 polymorphisms were associated with elevated C3 levels in our meta-analysis (standard mean difference, 0.50; 95% confidence interval, 0.30 to 0.71); the FEP with CG genotype of rs149898426 had higher C4 levels than that with GG genotypes (p = 0.005). Overall, these findings indicated that complement system altered in FEP and rs149898426 of C4 gene represented a genetic risk marker for schizophrenia likely through mediating complement system. Further studies with larger sample sizes needs to be validated.

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Section: Introductionmentioning

confidence: 99%

Associations Between Genotype and Peripheral Complement Proteins in First-Episode Psychosis: Evidences From C3 and C4

et al. 2021

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“…The CSMD1 protein has been shown to inhibit the complement system by promoting C3b/C4b degradation and preventing MAC formation ( Escudero-Esparza et al, 2013 ), interestingly, only in the classical and lectin pathways ( Kraus et al, 2006 ). Serum and plasma of SZ patients showed higher concentrations of complement proteins compared to controls ( Mayilyan et al, 2008 ; Arakelyan et al, 2011 ; Sória et al, 2012 ). Other studies looking into serum C3 and C4 concentrations reported mixed results in SZ patients ( Maes et al, 1997 ; Cazzullo et al, 1998 ; Li et al, 2016 ), indicating a need for standardization of complement protein collection and detection.…”

Section: Complement System In Neuropsychiatric Disordersmentioning

confidence: 82%

Dysregulation of complement system in neuropsychiatric disorders: A mini review

Sierra

Tripathi

Pillai

2022

Biomarkers in Neuropsychiatry

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“…Despite documented evidence that numerous CC dysregulations do occur in SCH [ 54 ], a recent meta-analysis found no significant differences in the levels of C3 or C4 between SCH patients and HC [ 53 ]. Likewise, while some studies revealed significantly higher levels of C3 concentrations in SCH patients as compared to HC [ 55 , 56 , 57 ], others found significantly lower levels of C3 in SCH [ 58 , 59 ] or no differences between the same patient population and controls [ 60 , 61 , 62 ]. Laskaris et al observed higher blood C3 and C4 levels in ultra-high risk (UHR) patients and increased C4 level among patients with SCH as compared to HC [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

Complement Activation Products in Patients with Chronic Schizophrenia

Rudkowski

Waszczuk

Tyburski

et al. 2023

JCM

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Evidence suggests a role of the immune system in the pathogenesis of a number of mental conditions, including schizophrenia (SCH). In terms of physiology, aside from its crucial protective function, the complement cascade (CC) is a critical element of the regeneration processes, including neurogenesis. Few studies have attempted to define the function of the CC components in SCH. To shed more light on this topic, we compared the levels of complement activation products (CAP) (C3a, C5a and C5b-9) in the peripheral blood of 62 patients with chronic SCH and disease duration of ≥ 10 years with 25 healthy controls matched for age, sex, BMI and smoking status. Concentrations of all the investigated CAP were elevated in SCH patients. However, after controlling for potential confounding factors, significant correlations were observed between SCH and C3a (M = 724.98 ng/mL) and C5a (M = 6.06 ng/mL) levels. In addition, multivariate logistic regression showed that C3a and C5b-9 were significant predictors of SCH. There were no significant correlations between any CAP and SCH symptom severity or general psychopathology in SCH patients. However, two significant links emerged between C3a and C5b-9 and global functioning. Increased levels of both complement activation products in the patient group as compared to healthy controls raise questions concerning the role of the CC in the etiology of SCH and further demonstrate dysregulation of the immune system in SCH patients.

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Increased serum levels of C3 and C4 in patients with schizophrenia compared to eutymic patients with bipolar disorder and healthy

Cited by 38 publications

References 5 publications

Associations Between Genotype and Peripheral Complement Proteins in First-Episode Psychosis: Evidences From C3 and C4

Associations Between Genotype and Peripheral Complement Proteins in First-Episode Psychosis: Evidences From C3 and C4

Dysregulation of complement system in neuropsychiatric disorders: A mini review

Complement Activation Products in Patients with Chronic Schizophrenia

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