title: Plasma protein biomarkers for depression and schizophrenia by multi analyte profiling of case-control collections.
abstract: Despite significant research efforts aimed at understanding the neurobiological underpinnings of psychiatric disorders, the diagnosis and the evaluation of treatment of these disorders are still based solely on relatively subjective assessment of symptoms. Therefore, biological markers which could improve the current classification of psychiatry disorders, and in perspective stratify patients on a biological basis into more homogeneous clinically distinct subgroups, are highly needed. In order to identify novel candidate biological markers for major depression and schizophrenia, we have applied a focused proteomic approach using plasma samples from a large case-control collection. Patients were diagnosed according to DSM criteria using structured interviews and a number of additional clinical variables and demographic information were assessed. Plasma samples from 245 depressed patients, 229 schizophrenic patients and 254 controls were submitted to multi analyte profiling allowing the evaluation of up to 79 proteins, including a series of cytokines, chemokines and neurotrophins previously suggested to be involved in the pathophysiology of depression and schizophrenia. Univariate data analysis showed more significant p-values than would be expected by chance and highlighted several proteins belonging to pathways or mechanisms previously suspected to be involved in the pathophysiology of major depression or schizophrenia, such as insulin and MMP-9 for depression, and BDNF, EGF and a number of chemokines for schizophrenia. Multivariate analysis was carried out to improve the differentiation of cases from controls and identify the most informative panel of markers. The results illustrate the potential of plasma biomarker profiling for psychiatric disorders, when conducted in large collections. The study highlighted a set of analytes as candidate biomarker signatures for depression and schizophrenia, warranting further investigation in independent collections.
authors.affiliation: Neurosciences Centre of Excellence in Drug Discovery, GlaxoSmithKline R&D, Verona, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Domenici
authors.forename: David R
authors.initials: DR
authors.lastname: Willé
authors.forename: Federica
authors.initials: F
authors.lastname: Tozzi
authors.forename: Inga
authors.initials: I
authors.lastname: Prokopenko
authors.forename: Sam
authors.initials: S
authors.lastname: Miller
authors.forename: Astrid
authors.initials: A
authors.lastname: McKeown
authors.forename: Claire
authors.initials: C
authors.lastname: Brittain
authors.forename: Dan
authors.initials: D
authors.lastname: Rujescu
authors.forename: Ina
authors.initials: I
authors.lastname: Giegling
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Turck
authors.forename: Florian
authors.initials: F
authors.lastname: Holsboer
authors.forename: Edward T
authors.initials: ET
authors.lastname: Bullmore
authors.forename: Lefkos
authors.initials: L
authors.lastname: Middleton
authors.forename: Emilio
authors.initials: E
authors.lastname: Merlo-Pich
authors.forename: Robert C
authors.initials: RC
authors.lastname: Alexander
authors.forename: Pierandrea
authors.initials: P
authors.lastname: Muglia
mesh_terms: D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D003866:Depressive Disorder / Q000097:blood* / Q000175:diagnosis; D006801:Humans; D015999:Multivariate Analysis; D011506:Proteins / Q000032:analysis* / Q000145:classification; D040901:Proteomics / Q000379:methods*; D012559:Schizophrenia / Q000097:blood* / Q000175:diagnosis
chemical_list: D015415:Biomarkers; D011506:Proteins