精神分裂症的背外侧前额叶皮层中N-乙酰天冬氨酸和谷氨酸盐的去耦

Title:Decoupling of N-Acetyl-Aspartate and Glutamate Within the Dorsolateral Prefrontal Cortex in Schizophrenia

Volume: 15 Issue: 2

Author(s): J.M. Coughlin, T. Tanaka, A. Marsman, H. Wang, S. Bonekamp, P.K. Kim, C. Higgs, M. Varvaris and R.A.E. Edden, M. Pomper, D. Schretlen, P.B. Barker and A. Sawa

Affiliation:

关键词: 前扣带皮层（ACC），背外侧前额叶皮层（DLPFC），谷氨酸盐，N-乙酰天冬氨酸（NAA），线粒体，氧化应激，氢核磁共振谱（[1H]MRS）

摘要: Aberrant function of glutamatergic pathways is likely to underlie the pathology of schizophrenia. Evidence of oxidative stress in the disease pathology has also been reported. N-Acetylaspartate (NAA) is metabolically linked to both cascades and may be a key marker in exploring the interconnection of glutamatergic pathways and oxidative stress. Several studies have reported positive correlation between the levels of NAA and Glx (the sum of glutamate and glutamine) in several brain regions in healthy subjects, by using proton magnetic resonance spectroscopy ([¹H]MRS). Interestingly, one research group recently reported decoupling of the relationship between NAA and Glx in the hippocampus of patients with schizophrenia. Here we report levels of NAA and Glx measured using [¹H]MRS, relative to the level of creatine (Cr) as an internal control. The dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) in 25 patients with schizophrenia and 17 matched healthy controls were studied. In DLPFC, NAA/Cr and Glx/Cr were significantly positively correlated in healthy controls after correction for the effect of age and smoking status and after correction for multiple comparisons (r= 0.627, P= 0.017). However, in patients with schizophrenia, the positive correlation between NAA/Cr and Glx/Cr was not observed even after correcting for these two variables (r= -0.330, P= 0.124). Positive correlation between NAA/Cr and Glx/Cr was not observed in the ACC in both groups. Decoupling of NAA and Glx in the DLPFC may reflect the interconnection of glutamatergic pathways and oxidative stress in the pathology of schizophrenia, and may possibly be a biomarker of the disease.

Cite this article as:

J.M. Coughlin, T. Tanaka, A. Marsman, H. Wang, S. Bonekamp, P.K. Kim, C. Higgs, M. Varvaris and R.A.E. Edden, M. Pomper, D. Schretlen, P.B. Barker and A. Sawa , Decoupling of N-Acetyl-Aspartate and Glutamate Within the Dorsolateral Prefrontal Cortex in Schizophrenia, Current Molecular Medicine 2015; 15 (2) . https://dx.doi.org/10.2174/1566524015666150303104811