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.
Keywords: Anterior cingulate cortex (ACC), dorsolateral prefrontal cortex (DLPFC), glutamate, N-acetyl-aspartate
(NAA), mitochondria, oxidative stress, proton magnetic resonance spectroscopy ([1H]MRS), schizophrenia (SZ).
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