Functional Outcome in People at High Risk for Psychosis Predicted by Thalamic Glutamate Levels and Prefronto-Striatal Activation
Functional Outcome in People at High Risk for Psychosis Predicted by Thalamic Glutamate Levels and Prefronto-Striatal Activation
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DOI：
10.1093/schbul/sbu115
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发表时间：
2015-03-01
影响因子：
6.6
通讯作者：
McGuire, Philip
中科院分区：
文献类型：
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作者：
Allen, Paul;Chaddock, Christopher A.;McGuire, Philip
对于决定精神病高危人群功能结果的神经生物学因素知之甚少。我们使用多模态神经成像来研究认知任务期间的皮质反应和丘脑谷氨酸水平是否与随后的功能结果相关。60名受试者参与了研究：27名健康对照（CTRL）和33名精神病高危（UHR）。在基线时，使用功能性磁共振成像（fMRI）测量语言流畅性任务期间的皮质反应，并使用质子磁共振波谱（1H-MRS）测量丘脑谷氨酸水平。然后对UHR受试者进行平均18个月的临床随访，并根据随访时的总体功能评估评分将其细分为“良好”和“不良”功能结局亚组。功能结果较差的UHR受试者比功能结果良好的UHR受试者表现出更大的皮质和皮质下激活。他们的丘脑谷氨酸水平也较低，并且丘脑谷氨酸水平与前额叶-纹状体激活之间呈负相关，这在良好的功能结果或对照组中不存在。在精神病高危人群中，他们随后的功能水平可能取决于他们首次进入临床服务时神经生理和神经化学功能受到干扰的程度。
Little is known about the neurobiological factors that determine functional outcome in people at high risk for psychosis. We use multimodal neuroimaging to investigate whether cortical responses during a cognitive task and thalamic glutamate levels were associated with subsequent functional outcome. Sixty subjects participated: 27 healthy controls (CTRL) and 33 at ultrahigh risk (UHR) for psychosis. At baseline, cortical responses during a verbal fluency task were measured using functional Magnetic Resonance Imaging (fMRI) and proton Magnetic Resonance Spectroscopy (1H-MRS) was used to measure thalamic glutamate levels. The UHR subjects were then followed clinically for a mean duration of 18 months, and subdivided into "good" and "poor" functional outcome subgroups according to their Global Assessment of Function score at follow-up. UHR subjects with a poor functional outcome showed greater cortical and subcortical activation than UHR subjects with a good functional outcome. They also had lower levels of thalamic glutamate and showed a negative relationship between thalamic glutamate levels and prefrontal-striatal activation that was not present in the good functional outcome or control groups. In people at high risk for psychosis, their subsequent level of functioning may depend on the extent to which neurophysiological and neurochemical function is perturbed when they first present to clinical services.