Serum S100B Protein is Specifically Related to White Matter Changes in Schizophrenia

Abstract

Background: Schizophrenia can be conceptualized as a form of dysconnectivity between brain regions.To investigate the neurobiological foundation of dysconnectivity, one approach is to analyze white matter structures, such as the pathology of fiber tracks. S100B is considered a marker protein for glial cells, in particular oligodendrocytes and astroglia, that passes the blood brain barrier and is detectable in peripheral blood. Earlier Studies have consistently reported increased S100B levels in schizophrenia. In this study, we aim to investigate associations between S100B and structural white matter abnormalities.Methods: We analyzed data of 17 unmedicated schizophrenic patients (first and recurrent episode) and 22 controls. We used voxel based morphometry (VBM) to detect group differences of white matter structures as obtained from T1-weighted MR-images and considered S100B serum levels as a regressor in an age-corrected interaction analysis.Results: S100B was increased in both patient subgroups. Using VBM, we found clusters indicating significant differences of the association between S100B concentration and white matter. Involved anatomical structures are the posterior cingulate bundle and temporal white matter structures assigned to the superior longitudinal fasciculus.Conclusions: S100B-associated alterations of white matter are shown to be existent already at time of first manifestation of psychosis and are distinct from findings in recurrent episode patients. This suggests involvement of S100B in an ongoing and dynamic process associated with structural brain changes in schizophrenia. However, it remains elusive whether increased S100B serum concentrations in psychotic patients represent a protective response to a continuous pathogenic process or if elevated S100B levels are actively involved in promoting structural brain damage.

MMP9/RAGE pathway overactivation mediates redox dysregulation and neuroinflammation, leading to inhibitory/excitatory imbalance: a reverse translation study in schizophrenia patients

“…This MMP9/RAGE mechanism is a primary interest as some evidence implicates MMP9 and RAGE in SZ pathophysiology. For instance, patient serum contains higher levels of AGEs and S100B than serum from healthy controls [76,77]. Different studies have reported conflicting results on the levels of sRAGE in serum, showing increased [30] or decreased sRAGE [77,78] in patient serum.…”

The S100B story: from biomarker to active factor in neural injury

“…The antipsychotics haloperidol and risperidone have been shown to be able to inhibit the secretion of S100B in C6 glioma cells following IL-6 stimulation: this result has been interpreted as supporting the involvement of inflammatory processes in schizophrenia (de Souza et al 2013). As an indirect indication that S100B may be involved in processes associated with structural brain changes in schizophrenia, a relationship between blood S100B levels and alterations in white matter (namely the posterior cingulate bundle and superior longitudinal fasciculus), as obtained from T1-weighted MR-images, has been reported in unmedicated schizophrenia patients (Milleit et al 2016).…”

“…As an indirect indication that S100B may be involved in processes associated with structural brain changes in schizophrenia, a relationship between blood S100B levels and alterations in white matter (namely the posterior cingulate bundle and superior longitudinal fasciculus), as obtained from T1‐weighted MR‐images, has been reported in unmedicated schizophrenia patients (Milleit et al . ).…”

White matter damage after traumatic brain injury: A role for damage associated molecular patterns

“…CSF levels of S100β correlated with white matter injury after pneumococcal meningitis [109] and endotoxin-induced periventricular white matter injury in preterm fetal sheep was associated with higher S100β levels [81]. Reduced tissue expression of S100β was observed in the corpus callosum of schizophrenia patients [110] whereas increased serum levels of S100β directly correlated with white matter injury in schizophrenic patients [111] and in asphyxiated preterm babies [112]. In line with these findings, acutely increased serum levels of S100β were associated with patient mortality and poor acute and chronic outcomes after severe TBI [113–119] and were predictive of cognitive function at 4 months after pediatric mild TBI [120].…”

“…Increased S100β and S100β auto-antibody serum levels were also observed in football players who had experienced repeated sub-concussive events and correlated with white matter changes and cognitive decline [121]. As extracranial sources of S100β do not affect serum levels in humans [122], reduced tissue expression likely reflects increased extracellular release due to pathological conditions [111]. Functionally, S100β inhibition reduced neurodegeneration [123] and S100β −/− mice or antibody-mediated neutralization of S100β attenuated microglial reactivity and improved memory function after experimental TBI [124].…”