Proteomic landscape of atypical antipsychotics clinical response in blood plasma from schizophrenia patients

ABSTRACT: Antipsychotics are the main line of treatment for schizophrenia, despite being effective only in about 50% of patients. Additionally, serious side effects may cause medication drop-out, aggravated by a lack of understanding about how these drugs act at molecular level. As proteomics is a suitable tool for studying multifactorial disorders, the main goal was to unravel signaling pathways in blood plasma associated with a positive treatment outcome for the atypical antipsychotics olanzapine and risperidone. Blood plasma was collected from schizophrenia patients six weeks after treatment (T6), and patients were classified as good or poor responders to olanzapine or risperidone, and then samples were compared to each patient's baseline (T0). All samples were analyzed using label-free quantitative shotgun proteomics. Samples were depleted of the 14 most abundant proteins in plasma, were digested, and then submitted to M-Class two-dimensional nano-liquid chromatography, coupled online to a Synapt G2-Si mass spectrometer. Data was obtained in MSE mode (data- independent acquisition) in combination with ion-mobility (HDMSE). The proteins found to be differentially abundant in good responders compared to poor responders for risperidone and olanzapine were functionally analyzed in silico using Ingenuity® Pathway Analysis and were found to be mostly involved with immune system functions. This data can contribute to better understand the biochemical signaling peripherally triggered by antipsychotic medication, and can eventually be used to help improve treatment outcome by predicting patient response as well as through the development of new medication or a combination of drugs that act on the immune system to reduce the duration of poor response periods in patients suffering with schizophrenia.

INSTRUMENT(S): Synapt MS

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

DISEASE(S): Paranoid Schizophrenia

SUBMITTER: Sheila Garcia-Rosa  

LAB HEAD: Daniel Martins-de-Souza

PROVIDER: PXD015049 | Pride | 2020-06-01

REPOSITORIES: Pride