Isobaric tags for relative and absolute quantitation in identifying proteins for clozapine treatment response in patients with schizophrenia: A preliminary study

Abstract

Objective: Schizophrenia is a mental disorder characterized by reduced social engagement, abnormal emotional expression, and a lack of motivation. Isobaric tags for relative and absolute quantitation (iTRAQ) are a novel proteomic technique. In this study, we intended to identify potential biomarkers for predicting clozapine treatment response using iTRAQ. Methods: We identified patients with schizophrenia that responded to a four-week treatment with clozapine. Patient's peripheral blood mononuclear cells (PBMC) were collected before and after treatment. iTRAQ-based proteomics analysis was done to identify differentially expressed proteins in PBMC before and after treatment. STRING analysis map was built, and a target protein was selected. Western blot validation was then done. Results: In 10 identified clozapine treatment-responsive patients, we screened 2,735 proteins. Nine downregulated proteins and 11 upregulated proteins were differentially expressed by 1.5-fold after clozapine treatment. STRING network analysis revealed a series of apolipoproteins, and only apolipoprotein A4 (APOA-IV) was selected for validation. Western blot validations showed that protein levels of APOA-IV were significantly most downregulated in the patient after clozapine treatment (p = 0.05). Conclusion: In this study, we integrated clinical observation data, bioinformational protein interaction analysis, and iTRAQ labeling to study proteomics in patients with schizophrenia successfully treated with clozapine. We suggest that APOA-IV protein can be a biomarker for predicting clozapine treatment response in patients with schizophrenia. But these results in this study need a larger sample size to be validated.

Keywords

• apolipoprotein a-iv
• biomarker
• itraq labeling
• protein-protein interaction analysis