Gamma synchrony: towards a translational biomarker for the treatment-resistant symptoms of schizophrenia.
Gamma synchrony: towards a translational biomarker for the treatment-resistant symptoms of schizophrenia.
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DOI：
10.1016/j.neuropharm.2011.02.007
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发表时间：
2012-03
影响因子：
4.7
通讯作者：
Siegel, Steven J.
中科院分区：
文献类型：
--
作者：
Gandal, Michael J.;Edgar, J. Christopher;Klook, Kerstin;Siegel, Steven J.
抗精神病药物在阴性症状和认知缺陷方面缺乏疗效是精神分裂症治疗的一个重大障碍。开发针对这些症状的新药需要适当的神经生物标记物，这些标记物可以在模式生物中进行研究，用于跟踪治疗反应，并提供对病理生理疾病机制的洞察。越来越多的证据表明，精神分裂症患者伽马频率范围(30-80赫兹)的神经振荡受到干扰。伽马同步已被证明调节了一系列感觉和认知功能，包括感知编码、选择性注意、突显和工作记忆--这些神经认知过程在精神分裂症中是功能失调的，在很大程度上难以治疗。本文综述了有关精神分裂症伽玛波段反应(GBR)的临床文献现状，重点介绍了静息和听觉范式。接下来，对研究伽玛波段活动的精神分裂症的临床前研究进行综述，以深入了解与这些缺陷相关的神经机制。我们的结论是，伽马同步性异常在精神分裂症中普遍存在，可能反映了基线皮质伽马同步性(“噪声”)的升高以及刺激诱发的GBR(“信号”)的减少。这样的模型可能反映了海马和皮质功能障碍，以及下游GABA能缺陷的谷氨酸能信号减少，但可能受精神分裂症所涉及的多巴胺能异常的影响较小。最后，我们认为，临床前模型中皮质信息流中类似的信噪比缺陷是针对精神分裂症治疗耐药症状的新药开发的有用靶点。
The lack of efficacy for antipsychotics with respect to negative symptoms and cognitive deficits is a significant obstacle for the treatment of schizophrenia. Developing new drugs to target these symptoms requires appropriate neural biomarkers that can be investigated in model organisms, be used to track treatment response, and provide insight into pathophysiological disease mechanisms. A growing body of evidence indicates that neural oscillations in the gamma frequency range (30–80 Hz) are disturbed in schizophrenia. Gamma synchrony has been shown to mediate a host of sensory and cognitive functions, including perceptual encoding, selective attention, salience, and working memory – neurocognitive processes that are dysfunctional in schizophrenia and largely refractory to treatment. This review summarizes the current state of clinical literature with respect to gamma band responses (GBRs) in schizophrenia, focusing on resting and auditory paradigms. Next, preclinical studies of schizophrenia that have investigated gamma band activity are reviewed to gain insight into neural mechanisms associated with these deficits. We conclude that abnormalities in gamma synchrony are ubiquitous in schizophrenia and likely reflect an elevation in baseline cortical gamma synchrony (‘noise’) coupled with reduced stimulus-evoked GBRs (‘signal’). Such a model likely reflects hippocampal and cortical dysfunction, as well as reduced glutamatergic signaling with downstream GABAergic deficits, but is probably less influenced by dopaminergic abnormalities implicated in schizophrenia. Finally, we propose that analogous signal-to-noise deficits in the flow of cortical information in preclinical models are useful targets for the development of new drugs that target the treatment-resistant symptoms of schizophrenia.
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影响因子：
14.8
作者：
Carlson, Greg C.;Coulter, Douglas A.
通讯作者：
Coulter, Douglas A.
影响因子：
3
作者：
Basar-Eroglu, Canan;Brand, Andreas;Schmiedt, Christina
通讯作者：
Schmiedt, Christina
影响因子：
3.5
作者：
Berretta, S;Lange, N;Benes, FM
通讯作者：
Benes, FM
影响因子：
3.8
作者：
Banerjee A;Macdonald ML;Borgmann-Winter KE;Hahn CG
通讯作者：
Hahn CG
影响因子：
--
作者：
Berger, H
通讯作者：
Berger, H