Thalamic Glutamate Levels as a Predictor of Cortical Response During Executive Functioning in Subjects at High Risk for Psychosis
Thalamic Glutamate Levels as a Predictor of Cortical Response During Executive Functioning in Subjects at High Risk for Psychosis
复制标题
DOI：
10.1001/archgenpsychiatry.2011.46
复制
发表时间：
2011-09-01
影响因子：
--
通讯作者：
McGuire, P. K.
中科院分区：
文献类型：
--
作者：
Fusar-Poli, P.;Stone, J. M.;McGuire, P. K.
内容：谷氨酸能神经传递的改变和大脑皮层功能障碍被认为是精神病的病理生理学核心，但这两个因素之间的关系尚不清楚。目的：探讨精神病高危人群执行功能时大脑谷氨酸水平与皮层反应的关系（即处于危险精神状态[ARMS]）。设计：受试者在进行语言流畅性任务时，使用功能性磁共振成像进行研究，和质子磁共振波谱法被用来测量他们的大脑区域谷氨酸水平。设置：Maudsley医院，伦敦，英国。患者和其他参与者：总共41名受试者：24例ARMS受试者和17例健康志愿者主要观察指标：局部脑激活（血氧水平依赖性反应）;前扣带回、左侧丘脑和左侧海马中的谷氨酸水平;以及扫描时的精神病理学评级。在语言流畅性任务中，ARMS受试者双侧额中回的激活程度高于对照组。ARMS组丘脑谷氨酸水平低于对照组。在ARMS组中，丘脑谷氨酸水平与右侧背外侧前额叶和左侧眶额皮质的激活呈负相关，但与右侧海马和双侧颞叶皮质的激活呈正相关。皮质激活和丘脑谷氨酸水平之间的关系也存在显著的组间差异，对照组在前额叶皮质、右侧海马和上级颞回中显示出与ARMS组相反的相关性。ARMS患者前额叶、海马和颞叶功能的改变与丘脑谷氨酸水平的降低有关，并且这种关系与健康对照不同。
Context: Alterations in glutamatergic neurotransmission and cerebral cortical dysfunction are thought to be central to the pathophysiology of psychosis, but the relationship between these 2 factors is unclear.Objective: To investigate the relationship between brain glutamate levels and cortical response during executive functioning in people at high risk for psychosis (ie, with an at-risk mental state [ARMS]).Design: Subjects were studied using functional magnetic resonance imaging while they performed a verbal fluency task, and proton magnetic resonance spectroscopy was used to measure their brain regional glutamate levels.Setting: Maudsley Hospital, London, England.Patients and Other Participants: A total of 41 subjects: 24 subjects with an ARMS and 17 healthy volunteers (controls).Main Outcome Measures: Regional brain activation (blood oxygen level-dependent response); levels of glutamate in the anterior cingulate, left thalamus, and left hippocampus; and psychopathology ratings at the time of scanning.Results: During the verbal fluency task, subjects with an ARMS showed greater activation than did controls in the middle frontal gyrus bilaterally. Thalamic glutamate levels were lower in the ARMS group than in control group. Within the ARMS group, thalamic glutamate levels were negatively associated with activation in the right dorsolateral prefrontal and left orbitofrontal cortex, but positively associated with activation in the right hippocampus and in the temporal cortex bilaterally. There was also a significant group difference in the relationship between cortical activation and thalamic glutamate levels, with the control group showing correlations in the opposite direction to those in the ARMS group in the prefrontal cortex and in the right hippocampus and superior temporal gyrus.Conclusions: Altered prefrontal, hippocampal, and temporal function in people with an ARMS is related to a reduction in thalamic glutamate levels, and this relationship is different from that in healthy controls.