fibrinopeptide-a and Schizophrenia

Schizophrenia is a psychiatric condition characterized by poor prognosis and severe symptoms that decrease the quality of life of patients. It is therefore important to develop rapid and reliable methods for early diagnosis. To achieve this aim, identification of accurate biomarkers will promote research into the mechanisms of schizophrenia and the design of effective diagnosis tools. Discriminative peptides in the serum of participants (277 schizophrenia patients and 294 healthy controls) were detected using the matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry (MALDI-TOF-MS). The diagnostic model for schizophrenia was validated using the ClinProTool software. Discrimination models were tested in the training set (200 schizophrenia patients and 200 healthy controls), and the robustness of the models was evaluated using the independent test set (77 cases and 94 controls). A total of 77 peaks were significantly different between schizophrenia patients and healthy controls with a signal-to-noise ratio of over 5. Among them, 35 peptides were down-regulated and 42 peptides were up-regulated in schizophrenia patients. With a cross-validation rate of 92.7% and a recognition capability rate of 96.5%, the supervised neural network comprising 25 discriminative peaks was found to be the most efficient model for schizophrenia diagnosis (sensitivity = 96.10%, specificity = 94.68%). Peptides at m/z = 2022.18 corresponded to complement C3f, and peptides at m/z = 1020.89, 1351.02, 1466.1 were identified as fragments of fibrinopeptide A. These two peptides may be potential biomarkers for schizophrenia in the Chinese population. The serum peptide levels present a potential clinical diagnostic tool for schizophrenia.

Topics: Adult; Algorithms; Biomarkers; Complement C3b; Down-Regulation; Female; Fibrinopeptide A; Humans; Male; Middle Aged; Neural Networks, Computer; Peptides; Proteome; Schizophrenia; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tandem Mass Spectrometry; Up-Regulation; Young Adult

Diagnosis of schizophrenia does not have a clear objective test at present, so we aimed to identify the potential biomarkers for the diagnosis of schizophrenia by comparison of serum protein profiling between first-episode schizophrenia patients and healthy controls. The combination of a magnetic bead separation system with matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF-MS) was used to analyze the serum protein spectra of 286 first-episode patients with schizophrenia, 41 chronic disease patients and 304 healthy controls. FlexAnlysis 3.0 and ClinProTools(TM) 2.1 software was used to establish a diagnostic model for schizophrenia. The results demonstrated that 10 fragmented peptides demonstrated an optimal discriminatory performance. Among these fragmented peptides, the peptide with m/z 1206.58 was identified as a fragment of fibrinopeptide A. Receiver operating characteristic analysis for m/z 1206.58 showed that the area under the curve was 0.981 for schizophrenia vs healthy controls, and 0.999 for schizophrenia vs other chronic disease controls. From our result, we consider that the analysis of serum protein spectrum using the magnetic bead separation system and MALDI-TOF/TOF-MS is an objective diagnostic tool. We conclude that fibrinopeptide A has the potential to be a biomarker for diagnosis of schizophrenia. This protein may also help to elucidate schizophrenia disease pathogenesis.

Topics: Adult; Biomarkers; Blood Proteins; Case-Control Studies; Female; Fibrinopeptide A; Humans; Male; Mass Spectrometry; Middle Aged; Schizophrenia; Young Adult