title: Plasma Metabolites Predict Severity of Depression and Suicidal Ideation in Psychiatric Patients-A Multicenter Pilot Analysis.
abstract: 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.
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Setoyama
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.|Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka, Japan.
authors.forename: Takahiro A
authors.initials: TA
authors.lastname: Kato
authors.affiliation: Molecular Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Osaka, Japan.|Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Hashimoto
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kunugi
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.|Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Hattori
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Hayakawa
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Mina
authors.initials: M
authors.lastname: Sato-Kasai
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Shimokawa
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Sachie
authors.initials: S
authors.lastname: Kaneko
authors.affiliation: National Center of Neurology and Psychiatry Hospital, Tokyo, Japan.
authors.forename: Sumiko
authors.initials: S
authors.lastname: Yoshida
authors.affiliation: Translational Medical Center, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Yu-Ichi
authors.initials: YI
authors.lastname: Goto
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Yasuda
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hidenaga
authors.initials: H
authors.lastname: Yamamori
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ohgidani
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Sagata
authors.affiliation: Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Miura
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Dongchon
authors.initials: D
authors.lastname: Kang
authors.affiliation: Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Kanba
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood; D001622:Betaine / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D002853:Chromatography, Liquid / Q000379:methods*; D019343:Citric Acid / Q000097:blood; D003404:Creatinine / Q000097:blood; D003863:Depression / Q000378:metabolism / Q000523:psychology*; D005260:Female; D006801:Humans; D000069550:Machine Learning; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D055432:Metabolomics / Q000379:methods*; D010865:Pilot Projects; D011569:Psychiatric Status Rating Scales; D057566:Self Report; D012720:Severity of Illness Index; D059020:Suicidal Ideation; D005680:gamma-Aminobutyric Acid / Q000097:blood
chemical_list: D015415:Biomarkers; D019343:Citric Acid; D001622:Betaine; D005680:gamma-Aminobutyric Acid; D003404:Creatinine; D020155:3-Hydroxybutyric Acid