title: Phosphoproteomic differences in major depressive disorder postmortem brains indicate effects on synaptic function.
abstract: There is still a lack in the molecular comprehension of major depressive disorder (MDD) although this condition affects approximately 10% of the world population. Protein phosphorylation is a posttranslational modification that regulates approximately one-third of the human proteins involved in a range of cellular and biological processes such as cellular signaling. Whereas phosphoproteome studies have been carried out extensively in cancer research, few such investigations have been carried out in studies of psychiatric disorders. Here, we present a comparative phosphoproteome analysis of postmortem dorsolateral prefrontal cortex tissues from 24 MDD patients and 12 control donors. Tissue extracts were analyzed using liquid chromatography mass spectrometry in a data-independent manner (LC-MS(E)). Our analyses resulted in the identification of 5,195 phosphopeptides, corresponding to 802 non-redundant proteins. Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls, being 20 differentially phosphorylated in at least 2 peptides. The majority of these phosphorylated proteins were associated with synaptic transmission and cellular architecture not only pointing out potential biomarker candidates but mainly shedding light to the comprehension of MDD pathobiology.
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, Cambridgeshire, UK. danms90@gmail.com
authors.forename: Daniel
authors.initials: D
authors.lastname: Martins-de-Souza
authors.forename: Paul C
authors.initials: PC
authors.lastname: Guest
authors.forename: Natacha
authors.initials: N
authors.lastname: Vanattou-Saifoudine
authors.forename: Hassan
authors.initials: H
authors.lastname: Rahmoune
authors.forename: Sabine
authors.initials: S
authors.lastname: Bahn
mesh_terms: D000328:Adult; D002853:Chromatography, Liquid; D019295:Computational Biology; D003865:Major Depressive Disorder / Q000473:pathology*; D034284:Dynamin I / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D010748:Phosphopeptides / Q000378:metabolism*; D010766:Phosphorylation; D011180:Postmortem Changes; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology; D025341:Principal Component Analysis; D040901:Proteomics; D055815:Young Adult
chemical_list: D010748:Phosphopeptides; D034284:Dynamin I