title: Proteomic changes in serum of first onset, antidepressant drug-naïve major depression patients.
abstract: Major depressive disorder (MDD) is a complex and multi-factorial disorder. Although genetic factors and other molecular aspects of MDD have been widely studied, the underlying pathological mechanisms are still mostly unknown. We sought to investigate the pathophysiology of MDD by identifying and characterising serum molecular differences and their correlation to symptom severity in first onset, antidepressant drug-naïve MDD patients. We performed an exploratory molecular profiling study on serum samples of MDD patients and controls using multiplex immunoassay and label-free liquid chromatography mass spectrometry in data independent mode (LC-MSE). We included two independent cohorts of first onset, antidepressant drug-naïve MDD patients (n = 23 and 15) and matched controls (n = 42 and 21) in our study in order to validate the results. The main outcome included the following list of circulatory molecules changing and/or correlating to symptom severity: angiotensin-converting enzyme, acute phase proteins (e.g. ferritin and serotransferrin), brain-derived neurotrophic factor, complement component C4-B, cortisol, cytokines (e.g. macrophage migration inhibitory factor and interleukin-16), extracellular newly identified receptor for advanced glycosylation end products-binding protein, growth hormone and superoxide dismutase-1. This study provides evidence of an increased pro-inflammatory and oxidative stress response, followed by a hyperactivation of the HPA-axis in the acute stages of first onset MDD, as well as a dysregulation in growth factor pathways. These findings help to elucidate MDD related pathways in more detail and further studies may lead to identification of novel drug targets, including components of the inflammatory and oxidative stress response.
authors.affiliation: Department of Chemical Engineering and Biotechnology,University of Cambridge,Cambridge,UK.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Stelzhammer
authors.affiliation: Department of Chemical Engineering and Biotechnology,University of Cambridge,Cambridge,UK.
authors.forename: Frieder
authors.initials: F
authors.lastname: Haenisch
authors.affiliation: Department of Chemical Engineering and Biotechnology,University of Cambridge,Cambridge,UK.
authors.forename: Man K
authors.initials: MK
authors.lastname: Chan
authors.affiliation: Department of Chemical Engineering and Biotechnology,University of Cambridge,Cambridge,UK.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Cooper
authors.affiliation: Department of Psychiatry,University of Magdeburg,Germany.
authors.forename: Johann
authors.initials: J
authors.lastname: Steiner
authors.affiliation: Department of Chemical Engineering and Biotechnology,University of Cambridge,Cambridge,UK.
authors.forename: Hannah
authors.initials: H
authors.lastname: Steeb
authors.affiliation: Department of Chemical Engineering and Biotechnology,University of Cambridge,Cambridge,UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Martins-de-Souza
authors.affiliation: Department of Chemical Engineering and Biotechnology,University of Cambridge,Cambridge,UK.
authors.forename: Hassan
authors.initials: H
authors.lastname: Rahmoune
authors.affiliation: Department of Chemical Engineering and Biotechnology,University of Cambridge,Cambridge,UK.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Guest
authors.affiliation: Department of Chemical Engineering and Biotechnology,University of Cambridge,Cambridge,UK.
authors.forename: Sabine
authors.initials: S
authors.lastname: Bahn
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001798:Blood Proteins / Q000378:metabolism*; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D003165:Complement System Proteins / Q000378:metabolism; D016207:Cytokines / Q000097:blood*; D003865:Major Depressive Disorder / Q000097:blood*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007118:Immunoassay; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D040901:Proteomics / Q000379:methods*; D011569:Psychiatric Status Rating Scales; D013223:Statistics as Topic
chemical_list: D001798:Blood Proteins; D016207:Cytokines; D003165:Complement System Proteins; D007703:Peptidyl-Dipeptidase A; D006854:Hydrocortisone