期刊
BIOLOGICAL PSYCHIATRY
卷 70, 期 2, 页码 169-174出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2011.01.033
关键词
J-resolved; megapress; magnetic resonance spectroscopy (MRS); neurotransmission
资金
- National Institute of Mental Health [K23MH079982, K24DA015116, R01MH079799]
- Shervert Frazier Research Institute at McLean Hospital
- Counter-Drug Technology Assessment Center, an office within the Office of National Drug Control Policy [DABT63-99-C]
- Army Contracting Agency
- Eli Lilly
- GlaxoSmithKline
- Roche
Background: Abnormalities in glutamatergic neurotransmission are implicated in several psychiatric disorders, but in vivo neurochemical studies of the glutamate (Glu) system have been hampered by a lack of adequate probes. By contrast, glutamine (Gln) and Glu can be quantified separately in proton magnetic resonance spectroscopy studies in vivo. Accumulating evidence suggests that the Gln/Glu ratio is a putative index of glutamatergic neurotransmission but interpretation of changes in the Gln/Glu ratio depends on the conditions of the system, including ammonia levels. Methods: Here, we explored whether variation in GLS1 (the gene encoding the brain isoform of glutaminase, which catalyzes Gln-to-Glu conversion) is associated with Gln/Glu measured in vivo in two brain regions (anterior cingulate cortex, parieto-occipital cortex). Results: A specific haplotype of four single nucleotide polymorphisms within GLS1 was significantly associated with Gln/Glu in the parieto-occipital cortex in an magnetic resonance spectroscopy-genetics dataset optimized for Gln/Glu detection (n = 42). This finding was replicated in a second magnetic resonance spectroscopy dataset that was optimized for gamma-aminobutyric acid detection where Gln and Glu measurements could still be extracted (n = 40). Conclusions: These findings suggest that genetic variation in a key component of glutamatergic machinery is associated with a putative in vivo index of glutamatergic neurotransmission. Thus, GLS1 genotype might provide insight into normal brain function and into the pathophysiology of many psychiatric conditions where glutamatergic neurotransmission has been implicated. It might also serve as a biomarker for predicting response to existing and novel therapeutic interventions in psychiatry that target glutamatergic neurotransmission.
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