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

Background: Previous studies of patients with bipolar disorder (BD) using magnetic resonance spectroscopy (MRS) have shown neurophysiological abnormalities related to the glutamate (Glu)-glutamine (Gin) 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 (1tBG) 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 1tBG. 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 1tBG. 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.