Plasma metabolites predict severity of depression and suicidal ideation in psychiatric patients-a multicenter pilot analysis

Daiki Setoyama, Takahiro A. Kato, Ryota Hashimoto, Hiroshi Kunugi, Kotaro Hattori, Kohei Hayakawa, Mina Sato-Kasai, Norihiro Shimokawa, Sachie Kaneko, Sumiko Yoshida, Yu Ichi Goto, Yuka Yasuda, Hidenaga Yamamori, Masahiro Ohgidani, Noriaki Sagata, Daisuke Miura, Dongchon Kang, Shigenobu Kanba

研究成果: Contribution to journalArticle査読

55 被引用数 (Scopus)

抄録

Evaluating the severity of depression (SOD), especially suicidal ideation (SI), is crucial in the treatment of not only patients with mood disorders but also psychiatric patients in general. SOD has been assessed on interviews such as the Hamilton Rating Scale for Depression (HAMD)-17, and/or self-administered questionnaires such as the Patient Health Questionnaire (PHQ)-9. However, these evaluation systems have relied on a person's subjective information, which sometimes lead to difficulties in clinical settings. To resolve this limitation, a more objective SOD evaluation system is needed. Herein, we collected clinical data including HAMD-17/PHQ-9 and blood plasma of psychiatric patients from three independent clinical centers. We performed metabolome analysis of blood plasma using liquid chromatography mass spectrometry (LC-MS), and 123 metabolites were detected. Interestingly, five plasma metabolites (3-hydroxybutyrate (3HB), betaine, citrate, creatinine, and gamma-aminobutyric acid (GABA)) are commonly associated with SOD in all three independent cohort sets regardless of the presence or absence of medication and diagnostic difference. In addition, we have shown several metabolites are independently associated with sub-symptoms of depression including SI. We successfully created a classification model to discriminate depressive patients with or without SI by machine learning technique. Finally, we produced a pilot algorithm to predict a grade of SI with citrate and kynurenine. The above metabolites may have strongly been associated with the underlying novel biological pathophysiology of SOD. We should explore the biological impact of these metabolites on depressive symptoms by utilizing a cross species study model with human and rodents. The present multicenter pilot study offers a potential utility for measuring blood metabolites as a novel objective tool for not only assessing SOD but also evaluating therapeutic efficacy in clinical practice. In addition, modification of these metabolites by diet and/or medications may be a novel therapeutic target for depression. To clarify these aspects, clinical trials measuring metabolites before/after interventions should be conducted. Larger cohort studies including non-clinical subjects are also warranted to clarify our pilot findings.

本文言語英語
論文番号e0165267
ジャーナルPloS one
11
12
DOI
出版ステータス出版済み - 12 2016

All Science Journal Classification (ASJC) codes

  • 生化学、遺伝学、分子生物学(全般)
  • 農業および生物科学(全般)
  • 一般

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