Discovery of serum protein biomarkers in drug-free patients with major depressive disorder.
Major depressive disorder (MDD) is a systemic and multifactorial disorder involving complex interactions between genetic predisposition and disturbances of various molecular pathways. Its underlying molecular pathophysiology remains unclear, and no valid and objective diagnostic tools for the condition are available.



We performed large-scale proteomic profiling to identify novel peripheral biomarkers implicated in the pathophysiology of MDD in 25 drug-free female MDD patients and 25 healthy controls. First, quantitative serum proteome profiles were obtained and analyzed by liquid chromatography-tandem mass spectrometry using serum samples from 10 MDD patients and 10 healthy controls. Next, candidate biomarker sets, including differentially expressed proteins from the profiling experiment and those identified in the literature, were verified using multiple-reaction monitoring in 25 patients and 25 healthy controls. The final panel of potential biomarkers was selected using multiparametric statistical analysis.



We identified a serum biomarker panel consisting of six proteins: apolipoprotein D, apolipoprotein B, vitamin D-binding protein, ceruloplasmin, hornerin, and profilin 1, which could be used to distinguish MDD patients from controls with 68% diagnostic accuracy. Our results suggest that modulation of the immune and inflammatory systems and lipid metabolism are involved in the pathophysiology of MDD.



Our findings of functional proteomic changes in the peripheral blood of patients with MDD further clarify the molecular biological pathway underlying depression. Further studies using larger, independent cohorts are needed to verify the role of these candidate biomarkers for the diagnosis of MDD.
Institute for Systems Biology, Seattle, WA, United States; Department of Applied Chemistry, College of Applied Science, Kyung Hee University, Yongin, Republic of Korea.
Min Young
MY
Lee
Department of Psychiatry, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Republic of Korea.
Eun Young
EY
Kim
Department of Neuropsychiatry, Dongguk University Medical School, Dongguk University International Hospital, Goyang, Republic of Korea.
Se Hyun
SH
Kim
Department of Applied Chemistry, College of Applied Science, Kyung Hee University, Yongin, Republic of Korea.
Kyung-Cho
KC
Cho
Department of Psychiatry, Seoul National University Bundang Hospital, Seongnam, Republic of Korea;; Seoul National Hospital, Seoul, Republic of Korea; Institute of Human Behavioral Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Kyooseob
K
Ha
Department of Applied Chemistry, College of Applied Science, Kyung Hee University, Yongin, Republic of Korea. Electronic address: kimkp@khu.ac.kr.
Kwang Pyo
KP
Kim
Department of Psychiatry, Seoul National University Hospital, Seoul, Republic of Korea; Institute of Human Behavioral Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: aym@snu.ac.kr.
Yong Min
YM
Ahn
D000328:Adult; D053299:Apolipoprotein B-100 / Q000097:blood; D053399:Apolipoproteins D / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001774:Blood Chemical Analysis; D002135:Calcium-Binding Proteins / Q000097:blood; D002570:Ceruloplasmin / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D003865:Major Depressive Disorder / Q000097:blood*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007381:Intermediate Filament Proteins / Q000097:blood; D051304:Profilins / Q000097:blood; D020543:Proteome; D011569:Psychiatric Status Rating Scales; D053719:Tandem Mass Spectrometry; D014809:Vitamin D-Binding Protein / Q000097:blood
C569471:APOB protein, human; C024328:APOD protein, human; D053299:Apolipoprotein B-100; D053399:Apolipoproteins D; D015415:Biomarkers; D002135:Calcium-Binding Proteins; C503908:HRNR protein, human; D007381:Intermediate Filament Proteins; C495738:PFN1 protein, human; D051304:Profilins; D020543:Proteome; D014809:Vitamin D-Binding Protein; D002570:Ceruloplasmin
Immune system; Inflammation; Lipid metabolism; Major depressive disorder; Proteomics