Abstract
Immunological explanatory approaches are becoming increasingly important in schizophrenia research. In this context, the function of the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCSFB) plays an essential role. Different adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), are key elements in sustaining the integrity of the BBB and BCSFB. The objectives of this study were to (1) compare the levels of different cell adhesion molecules in the CSF of patients with schizophrenia spectrum disorders to those of patients with unipolar depression and (2) analyze their association with the established markers of the BBB/BCSFB function (CSF total protein and albumin quotient (AQ)). Therefore, a total of 40 patients with schizophrenia spectrum disorder and 39 age- and sex-matched control patients with unipolar depression were analyzed. The levels of soluble ICAM-1 (s-ICAM-1), soluble VCAM-1 (s-VCAM-1), and plasminogen activator inhibitor 1 (PAI-1) in the CSF were measured using a magnetic bead multiplexing immunoassay. The levels of sICAM-1 (p < 0.001), sVCAM-1 (p < 0.001), and PAI-1 (p < 0.001) in the CSF were significantly higher in patients with schizophrenia spectrum disorder than in patients with unipolar depression. In addition, a significant correlation of sVCAM-1 levels with total protein concentrations (r = 0.454, p = 0.003) and AQ levels (r = 0.512, p = 0.001) in patients with schizophrenia spectrum disorders was observed. The results revealed that sICAM-1 and sVCAM-1 levels in the CSF were higher in patients with schizophrenia spectrum disorder than in those with depression. These circulating signaling molecules may indicate endothelial dysfunction causing impaired BBB/BCSFB function in patients with schizophrenia spectrum disorders. Consistent with this view, a highly significant correlation of sVCAM-1 with CSF protein and AQs was detected. Upregulation of these cell adhesion molecules might be indicative of a proinflammatory immune response underlying the BBB/BCSFB disturbance in a subgroup of patients with schizophrenia spectrum disorders. The significance of the study is limited by its retrospective research design and by the absence of a healthy control group. The assay used was not previously established for the measurement of CSF. Further translational and controlled studies of the role of different cell adhesion molecules in schizophrenia are needed.
Highlights
Immunological explanatory approaches are becoming increasingly important in schizophrenia research [1]
The levels of soluble intercellular adhesion molecule-1 (ICAM-1) (sICAM-1) (p < 0.001), soluble vascular cell adhesion molecule-1 (VCAM-1) (sVCAM-1) (p < 0.001), and plasminogen activator inhibitor 1 (PAI-1) (p < 0.001) in the cerebrospinal fluid (CSF) were significantly higher in the patients with schizophrenia spectrum disorder than in those with unipolar depression (Table 4)
Subgroup analyses between patients with schizoaffective disorder (n = 11) and the other patients from the schizophrenia spectrum disorder group (n = 29) had similar mean ages (z = −1.061, p = 0.289). Both groups did not differ in the concentrations of sICAM-1 (z = −0.939, p = 0.348), sVCAM-1 (z = −1.530, p = 0.126), and PAI-1 (z = −1.636, p = 0.102)
Summary
Immunological explanatory approaches are becoming increasingly important in schizophrenia research [1]. They can produce chemokines [19], and endothelial VCAM-1 is associated with age- and inflammation-induced microglia activation, impaired neurogenesis, and cognitive deficits These changes are diminished by the antagonization of VCAM-1 and can occur even without a disturbance of the BBB/BCSFB parameters or infiltration of immune cells [20]. Previous studies comparing patients with schizophrenia spectrum disorder and controls revealed contradictory findings on soluble ICAM-1 (sICAM-1) levels when obtained using different methods and samples [3] Two previous studies examining CSF samples found an association of sICAM-1-levels and BCSFB markers (total CSF protein and albumin quotient) and with clinical parameters (negative symptoms and duration of disease) [21,22]
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