Glutamatergic dysfunction linked to energy and membrane lipid metabolism in frontal and anterior cingulate cortices of never treated first-episode schizophrenia patients
Glutamatergic dysfunction linked to energy and membrane lipid metabolism in frontal and anterior cingulate cortices of never treated first-episode schizophrenia patients
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DOI：
10.1016/j.schres.2015.07.013
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发表时间：
2015-10
影响因子：
4.5
通讯作者：
S. Smesny;A. Gussew;N. Biesel;S. Schack;M. Walther;R. Rzanny;B. Milleit;Christian Gaser;T. Sobanski;C. Schultz;P. Amminger;U. Hipler;H. Sauer;J. Reichenbach
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作者：
S. Smesny;A. Gussew;N. Biesel;S. Schack;M. Walther;R. Rzanny;B. Milleit;Christian Gaser;T. Sobanski;C. Schultz;P. Amminger;U. Hipler;H. Sauer;J. Reichenbach
研究背景精神分裂症患者的额叶/前额叶和前扣带皮层（ACC）存在谷氨酸能功能障碍和膜脂及能量代谢的改变。尽管已经在动物身上进行了研究，但谷氨酸能功能和结构可塑性之间的假定联系尚未在人类大脑中直接进行研究。方法采用1H-和31 P-化学位移成像（CSI）技术，对精神分裂症患者的谷氨酸（Glu）、能量代谢和膜磷脂代谢进行检测对31例首次急性发作精神病患者和31例健康对照者的PCr、ATP和膜脂代谢进行了研究。协方差的多变量分析被用来评估疾病对谷氨酸的影响，并探讨谷氨酸的改变对磷脂和能量metabolites.ResultsGlu水平的患者增加在额叶和前额叶皮层双边和ACC. Higher谷氨酸与左额叶/前额叶PME和右额叶/前额叶PDE患者，这是没有观察到在健康对照组。相比之下，较高的谷氨酸水平与较低的PCr或ATP值在额叶/前额叶皮层双边和控制的右前扣带回。这是没有观察到在右ACC和左额叶/前额叶皮质的patients.ConclusionFrontal amatergic多动症是断开生理调节的能量代谢，并与增加膜破裂在右侧和增加膜恢复在左额叶和前额叶皮质区域。如先前的研究结果所示，这种病理学在首次急性疾病过程中可能是动态的，并可能与阴性症状和认知障碍相关。我们的研究结果强调了进一步研究精神病早期急性期神经保护治疗选择的重要性，甚至更好地用于精神病的超高风险状态。
BackgroundGlutamatergic dysfunction and altered membrane lipid and energy metabolism have been repeatedly demonstrated in the frontal/prefrontal and anterior cingulate cortex (ACC) in schizophrenia. Though having been already studied in animals, the presumed link between glutamatergic function and structural plasticity has not been investigated directly in the human brain yet. We measured glutamate (Glu), focal energy metabolism, and membrane phospholipid turnover to investigate main pathologies in those key brain regions of schizophrenia.Methods1H- and31P-Chemical Shift Imaging (CSI) was combined in a single session to assess Glu and markers of energy (PCr, ATP) and membrane lipid (PME, PDE) metabolism in 31 neuroleptic-naïve first acute onset psychosis patients and 31 matched healthy controls. Multivariate analyses of covariance were used to assess disease effects on Glu and to investigate the impact of Glu alterations on phospholipid and energy metabolites.ResultsGlu levels of patients were increased in the frontal and prefrontal cortex bilaterally and in the ACC. Higher Glu was associated with increased left frontal/prefrontal PME and right frontal/prefrontal PDE in patients, which was not observed in healthy controls. In contrast, higher Glu levels were associated with lower PCr or ATP values in the frontal/prefrontal cortex bilaterally and in the right ACC of controls. This was not observed in the right ACC and left frontal/prefrontal cortex of patients.ConclusionFrontal glutamatergic hyperactivity is disconnected from physiologically regulated energy metabolism and is associated with increased membrane breakdown in right and increased membrane restoration in left frontal and prefrontal cortical regions. As indicated by previous findings, this pathology is likely dynamic during the course of first acute illness and possibly associated with negative symptoms and cognitive impairment. Our findings underline the importance of further research on neuroprotective treatment options during the early acute or even better for the ultra-high risk state of psychotic illness.