Charting the Proteome Landscape in Major Psychiatric Disorders: From Biomarkers to Biological Pathways Towards Drug Discovery

Authors

Brisa S Fernandes
Yulin Dai
Peilin Jia
Zhongming Zhao

Publication Date

8-1-2022

Journal

European Neuropsychopharmacology

Abstract

Schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD) are major mental disorders that affect a significant proportion of the global population. Advancing our knowledge of the pathophysiology of these disorders and identifying biomarkers are urgent needs for developing objective diagnostic tests and new therapeutics. In this study, we performed a systematic review and then extracted, curated, and analyzed proteomics data from published studies, aiming to assess the proteome in peripheral blood of individuals with SZ, BD, or MDD. Then, we performed pathway and network analyses to illuminate the biological themes concatenated by the differentially expressed proteins by systematically interrogating the literature to uncover biological pathways with more robust biological meaning. We identified 486 differentially expressed proteins from 51 studies across the three disorders with 9,423 participants. The great majority of pathways were common to SZ, BD, and MDD. They were related to the immune system, including signaling by interleukins, Toll-like receptor signaling pathway, and complement cascade, and to signal transduction, notably MAPK1/MAPK3 signaling, PI3K-Akt Signaling Pathway, Focal Adhesion-PI3K-Akt-mTOR-signaling, rhodopsin-like receptors, GPCR signaling, and the JAK-STAT signaling pathway. Other shared pathways included advanced glycosylation end-product receptor signaling, Regulation of Insulin-like Growth Factor, cholesterol metabolism, and IL-17 signaling pathway. Pathways shared between SZ and BD were integrin cell-surface interactions, GRB2:SOS provides linkage to MAPK signaling for integrins, and syndecan interactions. Shared between BD and MDD were the NRF2 pathway and signaling by EGFR pathways. Our findings advance our understanding of the protein variations and associations with these disorders, which are useful for accelerating biomarker development and drug discovery.

Keywords

Biomarkers, Depressive Disorder, Major, Drug Discovery, Humans, Mental Disorders, Phosphatidylinositol 3-Kinases, Proteome, Proto-Oncogene Proteins c-akt

DOI

10.1016/j.euroneuro.2022.06.001

PMID

35763977

PMCID

PMC9378550

PubMedCentral® Posted Date

8-1-2023

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes