Cortico-Striatal GABAergic and Glutamatergic Dysregulations in Subjects at Ultra-High Risk for Psychosis Investigated with Proton Magnetic Resonance Spectroscopy.
Cortico-Striatal GABAergic and Glutamatergic Dysregulations in Subjects at Ultra-High Risk for Psychosis Investigated with Proton Magnetic Resonance Spectroscopy.
复制标题
DOI：
10.1093/ijnp/pyv105
复制
发表时间：
2015-09-12
期刊：
影响因子：
--
通讯作者：
Shungu DC
中科院分区：
文献类型：
--
作者：
de la Fuente-Sandoval C;Reyes-Madrigal F;Mao X;León-Ortiz P;Rodríguez-Mayoral O;Solís-Vivanco R;Favila R;Graff-Guerrero A;Shungu DC
精神分裂症患者的主要抑制性和兴奋性氨基酸递质系统γ-氨基丁酸和谷氨酸的调节异常已被描述。然而，目前还不清楚这些异常是否存在于精神错乱的超高风险人群中。23名超高风险抗精神病药物天真受试者和24名健康对照组受试者，年龄、性别、利手、吸烟和父母教育相匹配，在3T时进行了双侧尾状背核和内侧前额叶皮质的质子磁共振波谱扫描。使用标准的J-编辑技术获得γ-氨基丁酸和谷氨酸和谷氨酰胺的联合共振的水平，并表示为相对于同步获取的未被抑制的体素水信号的峰面积比。γ-氨基丁酸(P<；.001)和谷氨酰胺(P=.007)在超高危人群的背侧尾状核中的水平高于健康对照组。同样，在内侧前额叶皮质，超高风险组的γ-氨基丁酸(P=.03)和谷氨酸(P=.006)水平均高于健康对照组。在两个感兴趣的区域中，没有发现任何其他代谢物(N-乙酰天冬氨酸、总胆碱或总肌酸)的组间差异。这项研究首次提出了在超高风险受试者中，在与精神病的病理生理学有关的两个大脑区域中，γ-氨基丁酸和谷氨酸的异常升高的证据，证明了纵向研究的合理性，以评估这些神经递质异常是否可以作为转化为精神病的风险以及疾病进展和治疗反应的非侵入性生物标志物。
Dysregulations of the major inhibitory and excitatory amino neurotransmitter systems of γ-aminobutyric acid and glutamate, respectively, have been described in patients with schizophrenia. However, it is unclear whether these abnormalities are present in subjects at ultra-high risk for psychosis. Twenty-three antipsychotic naïve subjects at ultra-high risk and 24 healthy control subjects, matched for age, sex, handedness, cigarette smoking, and parental education, underwent proton magnetic resonance spectroscopy scans in the dorsal caudate bilaterally and the medial prefrontal cortex at 3T. Levels of γ-aminobutyric acid and of the combined resonance of glutamate and glutamine (Glx) were obtained using the standard J-editing technique and expressed as peak area ratios relative to the synchronously acquired unsuppressed voxel water signal. Higher levels of γ-aminobutyric acid (P<.001) and Glx (P=.007) were found in the dorsal caudate of the subjects at ultra-high risk than in the healthy controls. In the medial prefrontal cortex, likewise, both γ-aminobutyric acid (P=.03) and Glx (P=.006) levels were higher in the ultra-high risk group than in the healthy controls. No group differences were found for any of the other metabolites (N-acetylaspartate, total choline, or total creatine) in the 2 regions of interest. This study presents the first evidence of abnormal elevations, in subjects at ultra-high risk, of γ-aminobutyric acid and Glx in 2 brain regions that have been implicated in the pathophysiology of psychosis, warranting longitudinal studies to assess whether these neurotransmitter abnormalities can serve as noninvasive biomarkers of conversion risk to psychosis as well as of illness progression and treatment response.