Increased complement classical and mannan-binding lectin pathway activities in schizophrenia

The Complement System in Schizophrenia

“…The last is in accordance with the report of Sasaki et al 64 showing no significant changes (slight increase) in CH50 after 8 weeks' neuroleptic administration in acute exacerbating schizophrenia. In our recent studies, neither correlation of neuroleptic treatment with CH50 and C4 hemolytic activities, nor comparative analysis of neuroleptic-free versus medicated schizophrenic patients (approximate gender and age-matched group) revealed an association between CH50, and Cl, C2, C4 hemolytic activities, activities of MBL-MASP-1 and MBL-MASP-2 complexes and neuroleptic usage 67,68 Although Hakobyan et al 67 found more than a 50% decrease in C3 hemolytic activity in drug-free patients in comparison with medicated ones, Maes et al 71 reported no difference in plasma C3 and C4 concentration in such patient groups. From the few and restricted data presented here, it appears that there is no significant effect of neuroleptic-medication on the total complement activity and on individual component levels and activities, although given the trends for increases seen in some studies, and the fact that differences between patients and controls on total complement activity also reached only trend levels in most studies, a role for neuroleptic medication cannot be excluded.…”

“…79 The concentrations of these complexes show wide interindividual variation. 78 Thus, complement activation depends not only on MBL concentration and oligomeric state, but also on the quantity of MASP-2 and MASP-1 in serum, as after some certain threshold MASP-1 can compete out MASP-2 from binding to MBL 78 Taking into account our recent findings on exploration of MBL-MASP and L-ficolin-MASP complexes in schizophrenia, 61,68,69 it is likely that subtle interplay between MBL, ficolins and MASPs determines complex composition and modulation of the lectin pathway, which could be a very dynamic process depending on the current immune status of the organism and, particularly for schizophrenia, on the stage and course of illness, or on the presence of secondary factors such as coincidental infections, the impact of chronic smoking or effects of poor hygiene. To further explore the associations between raised lectin pathway activity and schizophrenia, we are undertaking multifactorial exploration of the whole lectin pathway, including measurement of H-ficolin and MASP-2 serum concentrations and genotype analyses of the components, as well as H-ficolin-MASP-1 and H-ficolin-MASP-2 complex activities in the same sample cohort.…”

“…[65][66][67] Significantly raised CH50 has been observed in a sample of schizophrenic patients, but only when they were in remission, a finding which is not consistent with the earlier studies. 68 Yet another recent investigation suggests raised classical pathway functional activity in a chronic schizophrenic patient cohort vs. healthy volunteers. 61 Thus, while these results do not implicate a replicable finding, it is conceivable that differences in disease stage and course of the patient groups investigated may influence complement total hemolytic activity.…”

“…61 This finding is in agreement with previous results, showing higher MBL-MASP-2 complex activity in patients in remission, there were no significant differences in MBL serum concentration and the activity of MBL-MASP-1 complexes in comparison with controls. 68 A year later we investigated the same parameters in chronic schizophrenic patients in an acute symptomatic exacerbation. 69 A modest increase in MBL level and significantly higher activities of MBL-MASP-1 and MBL-MASP-2 complexes were detected.…”

Cryoglobulins as indicators of upregulated immune response in schizophrenia

“…In certain diseased conditions the ability of Cgs to bind complement components and activate the complement system, the major mediator of the immune response, was observed [13,14]. On the other hand, several studies including our own results suggest about the involvement of the complement dysfunction in pathomechanisms of schizophrenia [15][16][17][18]. These findings generate interest in studying Cgs in schizophrenia.…”