TY - JOUR
T1 - Feasibility of investigating differential proteomic expression in depression
T2 - Implications for biomarker development in mood disorders
AU - Frye, M. A.
AU - Nassan, M.
AU - Jenkins, G. D.
AU - Kung, S.
AU - Veldic, M.
AU - Palmer, B. A.
AU - Feeder, S. E.
AU - Tye, S. J.
AU - Choi, D. S.
AU - Biernacka, J. M.
N1 - Funding Information:
Funding for the study was provided by Myriad RBM. All statistical analyses were completed by Mayo Clinic. MAF has received previous grant support from Assurex Health, Myriad, Pfizer, the National Institute of Mental Health (RO1 MH079261), the National Institute of Alcohol Abuse and Alcoholism (P20AA017830) and Mayo Foundation that did not support the work reported in this manuscript; has been a consultant to Janssen Global Services, Mitsubishi Tanabe Pharma Corporation, Myriad, Sunovion and Teva Pharmaceuticals; has received CME/Travel Support/ presentation from CME Outfitters and Sunovian. The remaining authors have no conflict of interest.
PY - 2015/12/8
Y1 - 2015/12/8
N2 - 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.
AB - 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.
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U2 - 10.1038/tp.2015.185
DO - 10.1038/tp.2015.185
M3 - Article
C2 - 26645624
AN - SCOPUS:84979099358
SN - 2158-3188
VL - 5
JO - Translational psychiatry
JF - Translational psychiatry
IS - 12
M1 - e689
ER -