1H-magnetic resonance spectroscopy study of glutamate-related abnormality in bipolar disorder

Hiroko Kubo; Masahito Nakataki; Satsuki Sumitani; Jun-Ichi Iga; Shusuke Numata; Naomi Kameoka; Shin-Ya Watanabe; Hidehiro Umehara; Makoto Kinoshita; Masatoshi Inoshita; Mai Tamaru; Masashi Ohta; Chiaki Nakayama-Yamauchi; Yasuhiro Funakoshi; Masafumi Harada; Tetsuro Ohmori

doi:10.1016/j.jad.2016.08.046

1H-magnetic resonance spectroscopy study of glutamate-related abnormality in bipolar disorder

J Affect Disord. 2017 Jan 15:208:139-144. doi: 10.1016/j.jad.2016.08.046. Epub 2016 Oct 8.

Authors

Hiroko Kubo¹, Masahito Nakataki², Satsuki Sumitani³, Jun-Ichi Iga⁴, Shusuke Numata¹, Naomi Kameoka¹, Shin-Ya Watanabe¹, Hidehiro Umehara¹, Makoto Kinoshita¹, Masatoshi Inoshita¹, Mai Tamaru¹, Masashi Ohta¹, Chiaki Nakayama-Yamauchi⁵, Yasuhiro Funakoshi⁵, Masafumi Harada⁶, Tetsuro Ohmori¹

Affiliations

¹ Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
² Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan. Electronic address: nktk@tokushima-u.ac.jp.
³ 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.
⁴ Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan; Department of Neuropsychiatry, Ehime University Graduate School of Medicine, Ehime, Japan.
⁵ Department of Medical Imaging, Institute of Biomedical Sciences, University of Tokushima Graduate School, Tokushima, Japan.
⁶ Department of Radiology and Radiation Oncology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.

PMID: 27770643
DOI: 10.1016/j.jad.2016.08.046

Abstract

Background: 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.

Methods: 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.

Results: 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.

Limitations: The present findings are cross-sectional and metabolites were measured in only two regions.

Conclusions: 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.

Keywords: Bipolar disorder; Glutamate; Glutamine; Lithium; Magnetic resonance spectroscopy; Sodium valproate.

Publication types

Clinical Trial

MeSH terms

Adult
Basal Ganglia / metabolism*
Biomarkers / metabolism
Bipolar Disorder / diagnosis*
Bipolar Disorder / metabolism
Case-Control Studies
Cross-Sectional Studies
Female
Glutamic Acid / metabolism*
Glutamine / metabolism*
Gyrus Cinguli / metabolism*
Humans
Magnetic Resonance Spectroscopy* / methods
Male
Middle Aged

Substances

Biomarkers
Glutamine
Glutamic Acid