Proteomische Untersuchungen aus dem Liquor cerebrospinalis schizophrener Patienten

Abstract

Schizophrenia is one of the most impairing and commonly prevalent mental disorders. Despite much research its pathogenesis remains unclear. The diagnosis of schizophrenia still fully relies on clinical criteria because no laboratory-chemical tests are available. Accordingly, the aim of this study was to identify biomarkers in cerebrospinal fluid (CSF) of schizophrenia patients. Such a process could potentially facilitate diagnosis of the disease and improve the understanding of its pathogenesis. Therefore, the cerebrospinal fluid of 12 patients with first manifestation of schizophrenia was compared with CSF of 12 healthy controls. In a first step, the brain specific proteins Tau, Beta-Amyloid, S100B and Orexin A were quantified using Enzyme-linked Immunosorbent Assay (ELISA) and Radioimmunoassay (RIA). No statistically significant differences were seen between the two groups. In order to identify differentially expressed proteins in the CSF proteome of schizophrenia patients, two-dimensional Difference in-Gel Electrophoresis (2D-DIGE) followed by mass spectrometric analysis was used. These experiments showed increased levels of Alpha-1-Antirypsin, Haptoglobin and Apolipoproteins A1 and A4 in CSF of schizophrenia patients. However, these initially seen differences could not be validated in bigger collective with independent methods (Western-Blot and ELISA). These proteins are mainly blood-derived and not specific for schizophrenia. Thus, in order to increase sensitivity for low concentrated brain-specific proteins in CSF some methodical optimizations like the preanalytical depletion of high concentrated blood-proteins are required. In conclusion, the present study’s findings indicate that schizophrenia only leads to relatively small alterations of the CSF proteome. As a consequence for further research, it is necessary to evaluate a bigger sample size and to include gel-free methods for better manageability.