Glutamate as a marker of cognitive function in schizophrenia: a proton spectroscopic imaging study at 4 Tesla.
Glutamate as a marker of cognitive function in schizophrenia: a proton spectroscopic imaging study at 4 Tesla.
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DOI：
10.1016/j.biopsych.2010.08.024
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发表时间：
2011-01-01
影响因子：
10.6
通讯作者：
Posse, Stefan
中科院分区：
文献类型：
--
作者：
Bustillo, Juan R.;Chen, Hongji;Gasparovic, Charles;Mullins, Paul;Caprihan, Arvind;Qualls, Clifford;Apfeldorf, William;Lauriello, John;Posse, Stefan
精神分裂症的认知缺陷可能与谷氨酸能功能障碍有关，但谷氨酸代谢的体内测量一直具有挑战性。我们研究了精神分裂症患者谷氨酸代谢与认知功能之间的关系。应用4特斯拉质子回波平面光谱成像技术对30例精神分裂症患者和28例健康志愿者进行了研究。在所有受试者中评估灰质和白色物质中谷氨酸+谷氨酰胺（Glx）、N-乙酰天冬氨酸化合物（NAAc）和肌醇（Ins）浓度以及广泛的神经心理功能。Glx与精神分裂症组的总体认知表现呈正相关（p=0.0006），约占方差的36%。在对照组中未发现相关性。组平均Glx水平在精神分裂症和对照组相似。与年龄匹配的对照组相比，年轻精神分裂症受试者（年龄<30岁; p=0.04）的皮质灰质中NAAc减少。与年龄匹配的对照组相比，老年精神分裂症受试者（年龄>30岁）的皮质灰质（p=0.002）和白色物质（p=0.02）的INS增加。虽然精神分裂症作为一个群体没有减少，但较低的Glx水平与疾病中的认知受损相关。这表明在精神分裂症中调节谷氨酸功能的机制具有异质性。脑功能储备减少的患者可能会进入更严重的脑功能减退状态，并产生认知后果。在老年受试者中，在疾病早期皮质灰质NAAc浓度降低并正常化，这与早期树突回缩和随后神经元堆积增加的过程一致。在疾病后期，Ins升高提示神经胶质受累。
Cognitive deficits in schizophrenia may be related to glutamatergic dysfunction, but in-vivo measurement of glutamate metabolism has been challenging. We examined the relationship between glutamate metabolism and cognitive function in schizophrenia. Thirty subjects with DSM-IV schizophrenia and 28 healthy volunteers, were studied using 4 Tesla proton echo planar spectroscopic imaging. Glutamate plus glutamine (Glx), N-acetyl-aspartate compounds (NAAc) and Inositol (Ins) concentrations in gray and white matter and broad neuropsychological function were assessed in all subjects. Glx was positively correlated with overall cognitive performance in the schizophrenia group (p=0.0006), accounting for about 36% of the variance. No correlation was found in controls. Group-averaged Glx levels were similar in schizophrenia and controls. NAAc was reduced in cortical gray matter in the younger schizophrenia subjects (age <30; p=0.04) compared to age-matched controls. Ins was increased in cortical gray (p=0.002) and white matter (p=0.02) in the older schizophrenia subjects (age>30) compared to age-matched controls. Although not reduced in schizophrenia as a group, lower Glx levels correlates with impaired cognition in the illness. This suggests heterogeneity in mechanisms that regulate glutamate function in schizophrenia. Patients with reduced glutamatergic reserves may be rendered into a more severe hypoglutamatergic state with cognitive consequences. Reduced cortical gray matter NAAc concentration early in the illness with normalization in older subjects, is consistent with a process of early dendritic retraction with subsequent increased neuronal packing. Later in the illness, Ins elevation suggests glial involvement.
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影响因子：
11
作者：
通讯作者：
--
影响因子：
4.5
作者：
ADDINGTON, D;ADDINGTON, J;SCHISSEL, B
通讯作者：
SCHISSEL, B
DOI：
10.1016/0005-2760(89)90265-8
发表时间：
1989-08-08
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
GLANVILLE, NT;BYERS, DM;PALMER, FBSC
通讯作者：
PALMER, FBSC
影响因子：
4.4
作者：
Baker, Eva H.;Basso, Gianpaolo;Horska, Alena
通讯作者：
Horska, Alena
影响因子：
6.6
作者：
Green, MF;Kern, RS;Mintz, J
通讯作者：
Mintz, J