Kubo Hiroko, Nakataki Masahito, Sumitani Satsuki, Iga Jun-Ichi, Numata Shusuke, Kameoka Naomi, Watanabe Shin-Ya, Umehara Hidehiro, Kinoshita Makoto, Inoshita Masatoshi, Tamaru Mai, Ohta Masashi, Nakayama-Yamauchi Chiaki, Funakoshi Yasuhiro, Harada Masafumi, Ohmori Tetsuro
Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
Department of Psychiatry, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan.
J Affect Disord. 2017 Jan 15;208:139-144. doi: 10.1016/j.jad.2016.08.046. Epub 2016 Oct 8.
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.
先前使用磁共振波谱（MRS）对双相情感障碍（BD）患者进行的研究显示，与谷氨酸（Glu）-谷氨酰胺（Gln）循环、膜周转和神经元完整性相关的神经生理异常，尽管结果既不一致也无定论。最近有报道称，Gln/Glu比值是量化神经元-胶质细胞相互作用和谷氨酸能代谢物平衡的最有用指标。在这项MRS研究中，我们使用高场MRI系统在更大样本的BD患者中阐明了代谢物的异常情况。
62名受试者（31例BD患者和31名健康对照[HC]）使用刺激回波采集模式（STEAM）序列对前扣带回皮质（ACC）和左侧基底神经节（ltBG）进行了3T质子MRS（1H-MRS）检查。
在验证数据质量后，使用重复测量协方差分析（ANCOVA）对20例BD患者和23名年龄及性别匹配的HC进行了比较。与HC组相比，BD组ACC中Gln、肌酸（Cr）、N-乙酰天门冬氨酸（NAA）、胆碱（Cho）水平升高，Gln与Glu的比值增加，ltBG中Gln和Cho增加。将BD患者仅限于心境正常的患者后，这些发现仍然存在。在消除锂（Li）和丙戊酸钠（VPA）的影响后，我们观察到ACC中谷氨酸能神经传递激活，但ltBG中未观察到。
本研究结果为横断面研究，且仅在两个区域测量了代谢物。
我们的结果支持BD患者在谷氨酸能神经传递、膜周转和神经元完整性方面存在广泛的代谢物变化。此外，Gln/Glu比值的升高表明ACC中谷氨酸能神经传递亢进是BD的疾病标志物。
