title: Feasibility of investigating differential proteomic expression in depression: implications for biomarker development in mood disorders.
abstract: The objective of this study was to determine whether proteomic profiling in serum samples can be utilized in identifying and differentiating mood disorders. A consecutive sample of patients with a confirmed diagnosis of unipolar (UP n=52) or bipolar depression (BP-I n=46, BP-II n=49) and controls (n=141) were recruited. A 7.5-ml blood sample was drawn for proteomic multiplex profiling of 320 proteins utilizing the Myriad RBM Discovery Multi-Analyte Profiling platform. After correcting for multiple testing and adjusting for covariates, growth differentiation factor 15 (GDF-15), hemopexin (HPX), hepsin (HPN), matrix metalloproteinase-7 (MMP-7), retinol-binding protein 4 (RBP-4) and transthyretin (TTR) all showed statistically significant differences among groups. In a series of three post hoc analyses correcting for multiple testing, MMP-7 was significantly different in mood disorder (BP-I+BP-II+UP) vs controls, MMP-7, GDF-15, HPN were significantly different in bipolar cases (BP-I+BP-II) vs controls, and GDF-15, HPX, HPN, RBP-4 and TTR proteins were all significantly different in BP-I vs controls. Good diagnostic accuracy (ROC-AUC⩾0.8) was obtained most notably for GDF-15, RBP-4 and TTR when comparing BP-I vs controls. While based on a small sample not adjusted for medication state, this discovery sample with a conservative method of correction suggests feasibility in using proteomic panels to assist in identifying and distinguishing mood disorders, in particular bipolar I disorder. Replication studies for confirmation, consideration of state vs trait serial assays to delineate proteomic expression of bipolar depression vs previous mania, and utility studies to assess proteomic expression profiling as an advanced decision making tool or companion diagnostic are encouraged.
authors.affiliation: Department of Psychiatry & Psychology, Mayo Clinic Depression Center, Mayo Clinic, Rochester, MN, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Frye
authors.affiliation: Department of Psychiatry & Psychology, Mayo Clinic Depression Center, Mayo Clinic, Rochester, MN, USA.
authors.forename: M
authors.initials: M
authors.lastname: Nassan
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: G D
authors.initials: GD
authors.lastname: Jenkins
authors.affiliation: Department of Psychiatry & Psychology, Mayo Clinic Depression Center, Mayo Clinic, Rochester, MN, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kung
authors.affiliation: Department of Psychiatry & Psychology, Mayo Clinic Depression Center, Mayo Clinic, Rochester, MN, USA.
authors.forename: M
authors.initials: M
authors.lastname: Veldic
authors.affiliation: Department of Psychiatry & Psychology, Mayo Clinic Depression Center, Mayo Clinic, Rochester, MN, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Palmer
authors.affiliation: Department of Psychiatry & Psychology, Mayo Clinic Depression Center, Mayo Clinic, Rochester, MN, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Feeder
authors.affiliation: Department of Psychiatry & Psychology, Mayo Clinic Depression Center, Mayo Clinic, Rochester, MN, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Tye
authors.affiliation: Department of Psychiatry & Psychology, Mayo Clinic Depression Center, Mayo Clinic, Rochester, MN, USA.|Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Choi
authors.affiliation: Department of Psychiatry & Psychology, Mayo Clinic Depression Center, Mayo Clinic, Rochester, MN, USA.|Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Biernacka
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001714:Bipolar Disorder / Q000097:blood*; D003937:Diagnosis, Differential; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000097:blood*; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D055815:Young Adult
chemical_list: D015415:Biomarkers