TY - JOUR
T1 - Plasma metabolome analysis of patients with major depressive disorder
AU - Kawamura, Noriyuki
AU - Shinoda, Kosaku
AU - Sato, Hajime
AU - Sasaki, Kazunori
AU - Suzuki, Makoto
AU - Yamaki, Kumi
AU - Fujimori, Tamaki
AU - Yamamoto, Hiroyuki
AU - Osei-Hyiaman, Douglas
AU - Ohashi, Yoshiaki
N1 - Funding Information:
There are consistent conflicts of interest. N.K. conducted the study with the exploratory cohort at National Center of Neurology and Psychiatry Japan (NCNP), which approved N.K. to submit this paper in this form. N.K. is an advisor to and financially supported by HMT, and conducted the studies with the preliminary and checking cohort with HMT at the Kawamura Clinic for General Practice (KCGP). Y.O. is a stockholder in and a board director of HMT; K. Sasaki, H.S., H.Y. and D.O.H. are all employees of HMT. T.F. is a stockholder in HMT and was an employee at the time of this study. K. Shinoda, K.Y., and M.S. were employees of HMT at the time of this study. The statement specified in the disclosure statement and COI form corresponds to each other.
Funding Information:
The authors acknowledge the guidance of Chris Turck, Sanford Markey, and Teruhiko Higuchi as well as the excellent technical support of Takamasa Ishikawa, Sumiko Kumaki, Tomomi Sato, Hiromi Onuma, Yumiko Igarashi, and Junji Abe, who operated the metabolomics facilities; and the superb technical expertise of Aya Hoshi, who operated the IC-FLD. The authors also express their sincere gratitude to the study subjects for providing plasma samples used in the study. This study was supported in part by: Human Metabolome Technologies Inc. (HMT); grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology, Japan (18390211); the New Energy and Industrial Technology Development Organization, Japan; and the Ministry of Economy, Trade, and Industry, Japan (23SH2010).
Publisher Copyright:
© 2018 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology
PY - 2018/5
Y1 - 2018/5
N2 - Aim: This study sought to characterize the plasma metabolite profiling of patients with major depressive disorder (MDD). Methods: Psychiatric assessments were made with the Structured Clinical Interview for DSM-IV Axis I Disorders. In the exploratory cohort, plasma metabolite profiles of 34 MDD patients and 31 mentally healthy controls were compared using capillary electrophoresis-mass spectrometry. Among the candidate metabolites, we focused on a metabolite showing the largest difference. The absolute concentrations were measured in two cohorts from a psychiatric primary care clinic to characterize the accuracy of the metabolite biomarker. Results: Among 23 metabolites significantly lower in the MDD group than in healthy controls, we focused on phosphoethanolamine (PEA) as a candidate. The reduction of PEA levels in MDD was checked in independent clinical sample sets. An ion-chromatography-fluorescence detection method was developed to measure plasma PEA levels. In the preliminary cohort, we examined 34 MDD and 43 non-MDD subjects. The area under the receiver–operator curve (AUC) was 0.92, with sensitivity/specificity greater than 88%, at a cut-off of 1.46 μM. In the checking cohort, with 10 MDD and 13 non-MDD subjects, AUC was 0.89, with sensitivity/specificity of 86% and 100%, respectively, at a cut-off of 1.48 μM. Plasma PEA inversely correlated with MDD severity, depressed mood, loss of interest, and psychomotor retardation. Conclusion: These results suggest that plasma PEA level could be a candidate biomarker of MDD in the clinical setting. Further studies comparing MDD and mentally healthy controls are needed to confirm the utility of PEA as a biomarker for depression.
AB - Aim: This study sought to characterize the plasma metabolite profiling of patients with major depressive disorder (MDD). Methods: Psychiatric assessments were made with the Structured Clinical Interview for DSM-IV Axis I Disorders. In the exploratory cohort, plasma metabolite profiles of 34 MDD patients and 31 mentally healthy controls were compared using capillary electrophoresis-mass spectrometry. Among the candidate metabolites, we focused on a metabolite showing the largest difference. The absolute concentrations were measured in two cohorts from a psychiatric primary care clinic to characterize the accuracy of the metabolite biomarker. Results: Among 23 metabolites significantly lower in the MDD group than in healthy controls, we focused on phosphoethanolamine (PEA) as a candidate. The reduction of PEA levels in MDD was checked in independent clinical sample sets. An ion-chromatography-fluorescence detection method was developed to measure plasma PEA levels. In the preliminary cohort, we examined 34 MDD and 43 non-MDD subjects. The area under the receiver–operator curve (AUC) was 0.92, with sensitivity/specificity greater than 88%, at a cut-off of 1.46 μM. In the checking cohort, with 10 MDD and 13 non-MDD subjects, AUC was 0.89, with sensitivity/specificity of 86% and 100%, respectively, at a cut-off of 1.48 μM. Plasma PEA inversely correlated with MDD severity, depressed mood, loss of interest, and psychomotor retardation. Conclusion: These results suggest that plasma PEA level could be a candidate biomarker of MDD in the clinical setting. Further studies comparing MDD and mentally healthy controls are needed to confirm the utility of PEA as a biomarker for depression.
KW - biomarker
KW - diagnosis
KW - major depressive disorder
KW - metabolomics
KW - phosphoethanolamine
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U2 - 10.1111/pcn.12638
DO - 10.1111/pcn.12638
M3 - Article
C2 - 29356314
AN - SCOPUS:85043267038
VL - 72
SP - 349
EP - 361
JO - Psychiatry and Clinical Neurosciences
JF - Psychiatry and Clinical Neurosciences
SN - 1323-1316
IS - 5
ER -