Schizophrenia is a chronic and debilitating psychiatric disorder for which there is still no biomarker. The diagnosis of the disease is based primarily on clinical interview with no biomolecular support which can be used to increase diagnosis confidence or to guide prognosis. Moreover, medication-resistant patients need to be subjected to long and unhelpful therapy trials before initiating clozapine, which is far from the goal of personalized and preventive medicine.
In the present project, we aim at analyzing the proteic and metabolic content of the peripheral blood mononuclear cells (PBMCs) of minimally medicated first-episode psychosis (FEP) patients, comparing with healthy controls, in order to depict which pathways may play a role at the onset of the disease.
To achieve this goal a state-of-the-art quantitative approach, SWATH-MS, was used for both proteomics and metabolomics analysis. In total, thousands of metabolites and proteins were quantified. After the application of quality and statistical filters, several proteins and metabolites were defined as differentially expressed between FEP and control samples. Multivariate analysis using the differentially expressed proteins and metabolites demonstrated that these were enough to distinguish between the study groups, and after functional analysis of these same proteins some pathways were highlighted as potentially interesting for further studies.
In the future, the results here discussed will be further pursued and the analysis of the proteomic and metabolomic signatures throughout the course of disease and treatment, as well the comparison with other major psychiatric disorders, will be addressed.
This work was financed by ERDF through COMPETE 2020 and Portuguese funds via FCT, under projects: POCI-01-0145-FEDER-007440, POCI-01-0145-FEDER-016428, POCI-01-0145-FEDER-30943 and POCI-01-0145-FEDER-016795; and by The National Mass Spectrometry Network (LISBOA-01-0145-FEDER-402-022125). CS was supported by PhD fellowship SFRH/BD/88419/2012, co-financed by the European Social Funds through the POCH and FCT.