Assessment of Complement Cascade Components in Patients With Bipolar Disorder

Abstract

Introduction: The immune system is undoubtedly involved in the pathogenesis of various psychiatric disorders, such as schizophrenia, bipolar disorder, or depression. Although its role is not fully understood, it appears that this area of research can help to understand the etiology of mental illness. One of the components of the human immune system is the complement system, which forms a part of the innate immune response. Physiologically, except for its essential protective role, it is a vital element in the regeneration processes, including neurogenesis. To date, few studies have tried to clarify the role of the complement cascade in mental disorders.Materials and Methods: We evaluated concentrations of C3a, C5a, and C5b-9 complement cascade components in the peripheral blood of 30 patients suffering from bipolar disorder (BD) for at least 10 years, in euthymia, who were not treated with lithium salts. In addition, we divided our study sample into BD type I (BD-I, 22 persons), and BD type II (BD-II, 8 patients). The control group consisted of 30 healthy volunteers matched for age, sex, BMI, and smoking habits.Results: Compared to healthy controls, BD patients had elevated concentrations of all the investigated components. Furthermore, in patients with BD-II, we observed higher concentrations of C5b-9 as compared to patients with BD-I. However, there was a significant effect of BD diagnosis only on the levels of C3a and C5a but not on the level of C5b-9 after adjustment for potential confounding factors.Conclusions: Increased concentrations of components C3a and C5a of the complement system in the investigated group as compared to healthy controls suggest involvement of the complement cascade in the pathogenesis of BD, and provides further evidence of immune system dysregulation in BD patients.

Peripheral complement proteins in schizophrenia: A systematic review and meta-analysis of serological studies

“…Dysregulation of the complement system may also be associated with phenotypes outside of the schizophrenia or psychosis spectrum. Complement protein changes have been observed in other mental disorders ( Comes et al, 2018 ; Druart and Le Magueresse, 2019 ) including depression ( Chen et al, 2015 ; Stelzhammer et al, 2014 ), bipolar disorder ( Reginia et al, 2018 ) and autism spectrum disorder ( Corbett et al, 2007 ; Fagan et al, 2017 ). Thus these changes may reflect shared molecular pathology and aetiological mechanisms between these clinical phenotypes ( Druart and Le Magueresse, 2019 ).…”

Complement Activation in 22q11.2 Deletion Syndrome

“…Indeed, 23 new studies on involvement of complement system in development of schizophrenia have been published in the time period 2008-2019, indicating that overall complement pathway activity appears to be elevated in schizophrenia [39]. Further, Reginia et al demonstrated increased concentrations of C3a and C5a in the peripheral blood of patients suffering from bipolar disorder as compared to healthy individuals [15]. They also observed higher concentrations of C5b-9 in patients with bipolar disorder type II as compared to patients with bipolar disorder type I.…”

“…Activation of the complement system has also been linked to obesity [10]. Moreover, dysregulation of complement has been demonstrated in both schizophrenia, bipolar disorders, and autism spectrum disorders (ASD), as involvement of the complement system in both synapse elimination and neuron migration in the developing brain has been recognized [11][12][13][14][15][16][17]. On the other hand, deficiency of complement components, including mannose-binding lectin (MBL), which is a part of lectin pathway, might increase the overall susceptibility to infectious disease [18].…”

ATP-Nlrp3 Inflammasome-Complement Cascade Axis in Sterile Brain Inflammation in Psychiatric Patients and its Impact on Stem Cell Trafficking

“…To address this question there are two recently described intrinsic enzymatic pathways including heme oxygenase-1 (HO-1) and inducible nitric oxide synthetize (iNOS) that are inhibitors of Nlrp3 inflammasome and they may control its over-activation [35,36]. To support this, HO-1 activators which possess anti-inflammatory effects have been proposed to treat psychiatric patients [37,38].…”