Assessment of Complement Cascade Components in Patients With Bipolar Disorder

Reginia, Artur; Kucharska-Mazur, Jolanta; Jabłoński, Marcin; Budkowska, Marta; Dołęgowska, Barbara; Sagan, Leszek; Misiak, Błażej; Ratajczak, Mariusz Z.; Rybakowski, Janusz; Samochowiec, Jerzy

doi:10.3389/fpsyt.2018.00614

Cited by 28 publications

(30 citation statements)

References 78 publications

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“…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 ).…”

Section: Discussionmentioning

confidence: 99%

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

Mongan

Sabherwal

Susai

et al. 2020

Schizophrenia Research

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Background There is renewed focus on the complement system in the pathogenesis of schizophrenia. In addition to providing aetiological insights, consistently dysregulated complement proteins in serum or plasma may have clinical utility as biomarkers. Methods We performed a systematic literature review searching PubMed, Embase and PsycINFO for studies measuring complement system activity or complement protein concentrations in serum or plasma from patients with schizophrenia compared to controls. Random-effects meta-analyses were performed to calculate pooled effect estimates (Hedges' g standardised mean difference [SMD]) for complement proteins whose concentrations were measured in three or more studies. The review was pre-registered on the PROSPERO database (CRD42018109012). Results Database searching identified 1146 records. Fifty-eight full-text articles were assessed for eligibility and 24 studies included. Seven studies measured complement system activity. Activity of the classical pathway did not differ between cases and controls in four of six studies, and conflicting results were noted in two studies of alternative pathway activity. Twenty studies quantified complement protein concentrations of which complement components 3 (C3) and 4 (C4) were measured in more than three studies. Meta-analyses showed no evidence of significant differences between cases and controls for 11 studies of C3 (SMD 0.04, 95% confidence interval [CI] -0.29–0.36) and 10 studies of C4 (SMD 0.10, 95% CI -0.21–0.41). Conclusions Serological studies provide mixed evidence regarding dysregulation of the complement system in schizophrenia. Larger studies of a longitudinal nature, focusing on early phenotypes, could provide further insights regarding the potential role of the complement system in psychotic disorders.

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Section: Discussionmentioning

confidence: 99%

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

Mongan

Sabherwal

Susai

et al. 2020

Schizophrenia Research

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“…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.…”

Section: Discussionmentioning

confidence: 99%

“…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].…”

Section: Introductionmentioning

confidence: 99%

Complement Activation in 22q11.2 Deletion Syndrome

et al. 2020

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The 22q11.2 deletion syndrome (22q11.2 del), also known as DiGeorge syndrome, is a genetic disorder with an estimated incidence of 1:3000 to 1:6000 births. These patients may suffer from affection of many organ systems with cardiac malformations, immunodeficiency, hypoparathyroidism, autoimmunity, palate anomalies, and psychiatric disorders being the most frequent. The importance of the complement system in 22q11.2 del has not been investigated. The objective of this study was to evaluate the complement system in relation to clinical and immunological parameters in patients. A national cohort of patients (n = 69) with a proven heterozygous deletion of chromosome 22q11.2 and a group of age and sex matched controls (n = 56) were studied. Functional capacity of the classical, lectin, and alternative pathways of the complement system as well as complement activation products C3bc and terminal complement complex (TCC) were accessed and correlated to clinical features. All patients in our study had normal complement activation in both classical and alternative pathways. The frequency of mannose-binding lectin deficiency was comparable to the normal population. The patients had significantly raised plasma levels of C3bc and a slight, but not significant, increase in TCC compared with controls. This increase was associated with the presence of psychiatric disorders in patients. The present study shows no complement deficiencies in 22q11.2 deletion syndrome. On the contrary, there are signs of increased complement activation in these patients. Complement activation is particularly associated with the presence of psychiatric disorders.Journal of Clinical Immunology (2020) 40:515-523Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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“…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].…”

Section: Nlrp3 Inflammasome As a Cogwheel/gear That Connects Purinergmentioning

confidence: 99%

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

Ratajczak

Mack

Bujko

et al. 2019

Stem Cell Rev and Rep

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Recent evidence indicates that the occurrence of psychiatric disorders in patients is linked to a local Bsterile^inflammation of brain or due to a systemic inflammation process that affects the central nervous system. This is supported by the observation that in peripheral blood of psychotic patients are detectable several mediators and markers of inflammation as well as clinical data on correlations between systemic chronic inflammatory processes and psychiatric disorders. This may explain why some reported anti-inflammatory treatment strategies have beneficial effects on ameliorating psychotic events. In this review we will present a concept that aberrant purinergic signaling and increases in extracellular level of adenosine triphosphate (ATP) in the brain parenchyma may lead to activation of Nlrp3 inflammasome in microglia cells and as a consequence microglia released danger associated molecular pattern (DAMP) proteins activate complement cascade (ComC) in mannan binding lectin (MBL)dependent manner. Activation of ATP-Nlrp3 inflammasome-ComC axis may also orchestrate trafficking of stem cells released from bone marrow into peripheral blood observed in psychotic patients. Based on this, the ATP-Nlrp3 inflammasome-ComC axis may become a target for new therapeutic approaches, which justifies the development and clinical application of efficient antiinflammatory treatment strategies targeting this axis in psychiatry.

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Assessment of Complement Cascade Components in Patients With Bipolar Disorder

Cited by 28 publications

References 78 publications

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

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

Complement Activation in 22q11.2 Deletion Syndrome

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

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