title: 1H-magnetic resonance spectroscopy study of glutamate-related abnormality in bipolar disorder.
abstract: Previous studies of patients with bipolar disorder (BD) using magnetic resonance spectroscopy (MRS) have shown neurophysiological abnormalities related to the glutamate (Glu)-glutamine (Gln) cycle, membrane turnover, and neuronal integrity, although the results were neither consistent nor conclusive. Recently it has been reported the Gln/Glu ratio is the most useful index, quantifying neuronal-glial interactions and the balance of glutamatergic metabolites In this MRS study, we elucidated the abnormalities of metabolites in a larger sample of patients with BD with a high-field MRI system.
  
  
  
  Sixty-two subjects (31 patients with BD and 31 healthy controls [HC]) underwent 3T proton MRS (1H-MRS) of the anterior cingulate cortex (ACC) and left basal ganglia (ltBG) using a stimulated echo acquisition mode (STEAM) sequence.
  
  
  
  After verifying the data quality, 20 patients with BD and 23 age- and gender-matched HCs were compared using repeated-measures analysis of covariance (ANCOVA). Compared to the HC group, the BD group showed increased levels of Gln, creatine (Cr), N-acetyl aspartate (NAA), choline (Cho), and an increased ratio of Gln to Glu in the ACC, and increased Gln and Cho in the ltBG. These findings remained after the participants with BD were limited to only euthymic patients. After removing the influence of lithium (Li) and sodium valproate (VPA), we observed activated glutamatergic neurotransmission in the ACC but not in the ltBG.
  
  
  
  The present findings are cross-sectional and metabolites were measured in only two regions.
  
  
  
  Our results support a wide range of metabolite changes in patients with BD involved in glutamatergic neurotransmission, membrane turnover, and neuronal integrity. Moreover, the elevation of Gln/Glu ratio suggested that hyperactivity of glutamatergic neurotransmission in the ACC is a disease marker for BD.
authors: Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors: Hiroko
authors: H
authors: Kubo
authors: Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan. Electronic address: nktk@tokushima-u.ac.jp.
authors: Masahito
authors: M
authors: Nakataki
authors: Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan; Department of Support for Students with Special Needs, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors: Satsuki
authors: S
authors: Sumitani
authors: Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan; Department of Neuropsychiatry, Ehime University Graduate School of Medicine, Ehime, Japan.
authors: Jun-Ichi
authors: JI
authors: Iga
authors: Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors: Shusuke
authors: S
authors: Numata
authors: Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors: Naomi
authors: N
authors: Kameoka
authors: Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors: Shin-Ya
authors: SY
authors: Watanabe
authors: Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors: Hidehiro
authors: H
authors: Umehara
authors: Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors: Makoto
authors: M
authors: Kinoshita
authors: Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors: Masatoshi
authors: M
authors: Inoshita
authors: Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors: Mai
authors: M
authors: Tamaru
authors: Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors: Masashi
authors: M
authors: Ohta
authors: Department of Medical Imaging, Institute of Biomedical Sciences, University of Tokushima Graduate School, Tokushima, Japan.
authors: Chiaki
authors: C
authors: Nakayama-Yamauchi
authors: Department of Medical Imaging, Institute of Biomedical Sciences, University of Tokushima Graduate School, Tokushima, Japan.
authors: Yasuhiro
authors: Y
authors: Funakoshi
authors: Department of Radiology and Radiation Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors: Masafumi
authors: M
authors: Harada
authors: Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
authors: Tetsuro
authors: T
authors: Ohmori
mesh_terms: D000328:Adult; D001479:Basal Ganglia / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001714:Bipolar Disorder / Q000175:diagnosis* / Q000378:metabolism; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006179:Gyrus Cinguli / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008875:Middle Aged
chemical_list: D015415:Biomarkers; D005973:Glutamine; D018698:Glutamic Acid
keywords: Bipolar disorder; Glutamate; Glutamine; Lithium; Magnetic resonance spectroscopy; Sodium valproate