超高危精神病个体的脑谷氨酸和γ-氨基丁酸水平及其与临床症状和认知的关系。
Cerebral Glutamate and Gamma-Aminobutyric Acid Levels in Individuals at Ultra-high Risk for Psychosis and the Association With Clinical Symptoms and Cognition.
机构信息
Copenhagen Research Center for Mental Health, Mental Health Center Copenhagen, Copenhagen University Hospital, Hellerup, Denmark; Center for Neuropsychiatric Schizophrenia Research and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Center, University of Copenhagen, Glostrup, Denmark; Functional Imaging Unit, Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital Rigshospitalet, Glostrup, Denmark.
Copenhagen Research Center for Mental Health, Mental Health Center Copenhagen, Copenhagen University Hospital, Hellerup, Denmark.
出版信息
Biol Psychiatry Cogn Neurosci Neuroimaging. 2020 Jun;5(6):569-579. doi: 10.1016/j.bpsc.2019.12.005. Epub 2019 Dec 19.
BACKGROUND
Studies examining glutamate or gamma-aminobutyric acid (GABA) in ultra-high risk for psychosis (UHR) and the association with pathophysiology and cognition have shown conflicting results. We aimed to determine whether perturbed glutamate and GABA levels in the anterior cingulate cortex and glutamate levels in the left thalamus were present in UHR individuals and to investigate associations between metabolite levels and clinical symptoms and cognition.
METHODS
We included 122 UHR individuals and 60 healthy control subjects. Participants underwent proton magnetic resonance spectroscopy to estimate glutamate and GABA levels and undertook clinical and cognitive assessments.
RESULTS
We found no differences in metabolite levels between UHR individuals and healthy control subjects. In UHR individuals, we found negative correlations in the anterior cingulate cortex between the composite of glutamate and glutamine (Glx) and the Comprehensive Assessment of At-Risk Mental States composite score (p = .04) and between GABA and alogia (p = .01); positive associations in the anterior cingulate cortex between glutamate (p = .01) and Glx (p = .01) and spatial working memory and between glutamate (p = .04), Glx (p = .04), and GABA (p = .02) and set-shifting; and a positive association in the thalamus between glutamate and attention (p = .04). No associations between metabolites and clinical or cognitive scores were found in the healthy control subjects.
CONCLUSIONS
An association between glutamate and GABA levels and clinical symptoms and cognition found only in UHR individuals suggests a loss of the normal relationship between metabolite levels and cognitive function. Longitudinal studies with investigation of clinical and cognitive outcome and the association with baseline levels of glutamate and GABA could illuminate whether glutamatergic and GABAergic dysfunction predicts clinical outcome.
背景
研究谷氨酸或γ-氨基丁酸（GABA）在超高风险精神分裂症（UHR）中的作用以及与病理生理学和认知的关系，结果存在矛盾。我们旨在确定 UHR 个体是否存在前扣带回皮层谷氨酸和 GABA 水平紊乱以及左侧丘脑谷氨酸水平紊乱，并探讨代谢物水平与临床症状和认知之间的关系。
方法
我们纳入了 122 名 UHR 个体和 60 名健康对照者。参与者接受质子磁共振波谱分析以估计谷氨酸和 GABA 水平，并进行临床和认知评估。
结果
我们未发现 UHR 个体和健康对照组之间代谢物水平存在差异。在 UHR 个体中，我们在前扣带回皮层中发现谷氨酸和谷氨酰胺（Glx）的复合与风险综合评估状态复合评分之间存在负相关（p =.04），以及 GABA 与语量减少之间存在负相关（p =.01）；在前扣带回皮层中存在正相关，谷氨酸（p =.01）和 Glx（p =.01）与空间工作记忆之间，以及谷氨酸（p =.04）、Glx（p =.04）和 GABA（p =.02）与转换注意之间存在正相关；在前丘脑皮层中，谷氨酸与注意力之间存在正相关（p =.04）。在健康对照组中，未发现代谢物与临床或认知评分之间存在相关性。
结论
仅在 UHR 个体中发现谷氨酸和 GABA 水平与临床症状和认知之间存在关联，这表明代谢物水平与认知功能之间的正常关系丧失。进行纵向研究，调查临床和认知结局以及与谷氨酸和 GABA 基线水平的关系，可以阐明谷氨酸能和 GABA 能功能障碍是否可以预测临床结局。
Zotero 插件