Yuki Kageyama1,2, Takaoki Kasahara1, Hiromasa Morishita3, Nobuko Mataga3, Yasuhiko Deguchi2, Munehide Tani4, Kenji Kuroda5, Kotaro Hattori6, Sumiko Yoshida6,7, Koki Inoue2, Tadafumi Kato1. 1. Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, Saitama, Japan. 2. Department of Neuropsychiatry, Graduate School of Medicine, Osaka City University, Osaka, Japan. 3. Research Resources Center, RIKEN Brain Science Institute, Saitama, Japan. 4. Tani Mental Clinic, Osaka, Japan. 5. Department of Psychiatry, Hannan Hospital, Osaka, Japan. 6. Medical Genome Center, National Center of Neurology and Psychiatry, Tokyo, Japan. 7. Department of Laboratory Medicine, National Center of Neurology and Psychiatry Hospital, Tokyo, Japan.
Abstract
AIM: There is an urgent need for diagnostic biomarkers of bipolar disorder (BD) and schizophrenia (SZ); however, confounding effects of medication hamper biomarker discovery. In this study, we conducted metabolome analyses to identify novel plasma biomarkers in drug-free patients with BD and SZ. METHODS: We comprehensively analyzed plasma metabolites using capillary electrophoresis time-of-flight mass spectrometry in patients with SZ (n = 17), BD (n = 6), and major depressive disorder (n = 9) who had not received psychotropics for at least 2 weeks, and in matched healthy controls (n = 19). The results were compared with previous reports, or verified in an independent sample set using an alternative analytical approach. RESULTS: Lower creatine level and higher 2-hydroxybutyric acid level were observed in SZ than in controls (uncorrected P = 0.016 and 0.043, respectively), whereas they were unaltered in a previously reported dataset. Citrulline was nominally significantly decreased in BD compared to controls (uncorrected P = 0.043); however, this finding was not replicated in an independent sample set of medicated patients with BD. N-methyl-norsalsolinol, a metabolite of dopamine, was suggested as a candidate biomarker of BD; however, it was not detected by the other analytical method. Levels of betaine, a previously reported candidate biomarker of schizophrenia, were unchanged in the current dataset. CONCLUSION: Our preliminary findings suggest that the effect of confounding factors, such as duration of illness and medication, should be carefully controlled when searching for plasma biomarkers. Further studies are required to establish robust biomarkers for these disorders.
AIM: There is an urgent need for diagnostic biomarkers of bipolar disorder (BD) and schizophrenia (SZ); however, confounding effects of medication hamper biomarker discovery. In this study, we conducted metabolome analyses to identify novel plasma biomarkers in drug-free patients with BD and SZ. METHODS: We comprehensively analyzed plasma metabolites using capillary electrophoresis time-of-flight mass spectrometry in patients with SZ (n = 17), BD (n = 6), and major depressive disorder (n = 9) who had not received psychotropics for at least 2 weeks, and in matched healthy controls (n = 19). The results were compared with previous reports, or verified in an independent sample set using an alternative analytical approach. RESULTS: Lower creatine level and higher 2-hydroxybutyric acid level were observed in SZ than in controls (uncorrected P = 0.016 and 0.043, respectively), whereas they were unaltered in a previously reported dataset. Citrulline was nominally significantly decreased in BD compared to controls (uncorrected P = 0.043); however, this finding was not replicated in an independent sample set of medicated patients with BD. N-methyl-norsalsolinol, a metabolite of dopamine, was suggested as a candidate biomarker of BD; however, it was not detected by the other analytical method. Levels of betaine, a previously reported candidate biomarker of schizophrenia, were unchanged in the current dataset. CONCLUSION: Our preliminary findings suggest that the effect of confounding factors, such as duration of illness and medication, should be carefully controlled when searching for plasma biomarkers. Further studies are required to establish robust biomarkers for these disorders.
Authors: Johannes Hebebrand; Triinu Peters; Dick Schijven; Moritz Hebebrand; Corinna Grasemann; Thomas W Winkler; Iris M Heid; Jochen Antel; Manuel Föcker; Lisa Tegeler; Lena Brauner; Roger A H Adan; Jurjen J Luykx; Christoph U Correll; Inke R König; Anke Hinney; Lars Libuda Journal: Mol Metab Date: 2018-04-03 Impact factor: 7.422