Trombka David, Meiron Oded
Brain and Memory Laboratory, Faculty of Education, Bar-Ilan University, Ramat Gan 5290002, Israel.
Int J Mol Sci. 2025 Aug 4;26(15):7514. doi: 10.3390/ijms26157514.
Schizophrenia (SZ) is a complex neuropsychiatric disorder characterized by heterogeneous symptoms, relatively poor clinical outcome, and widespread disruptions in neural connectivity and oscillatory dynamics. This article attempts to review current evidence linking genomic and proteomic alterations with aberrant neural oscillations observed in SZ, including aberrations in all oscillatory frequency bands obtained via human EEG. The numerous genes discussed are mainly involved in modulating synaptic transmission, synaptic function, interneuron excitability, and excitation/inhibition balance, thereby influencing the generation and synchronization of neural oscillations at specific frequency bands (e.g., gamma frequency band) critical for different cognitive, emotional, and perceptual processes in humans. The review highlights how polygenic influences and gene-circuit interactions underlie the neural oscillatory and connectivity abnormalities central to SZ pathophysiology, providing a framework for future research on common genetic-neural function interactions and on potential therapeutic interventions targeting local and global network-level neural dysfunction in SZ patients. As will be discussed, many of these genes affecting neural oscillations in SZ also affect other neurological disorders, ranging from autism to epilepsy. In time, it is hoped that future research will show why the same genetic anomaly leads to one illness in one person and to another illness in a different person.
精神分裂症(SZ)是一种复杂的神经精神疾病,其特征为症状异质性、临床预后相对较差,以及神经连接和振荡动力学广泛紊乱。本文试图综述当前将基因组和蛋白质组改变与SZ中观察到的异常神经振荡联系起来的证据,包括通过人类脑电图获得的所有振荡频段的异常。所讨论的众多基因主要参与调节突触传递、突触功能、中间神经元兴奋性以及兴奋/抑制平衡,从而影响对人类不同认知、情感和感知过程至关重要的特定频段(如γ频段)神经振荡的产生和同步。该综述强调了多基因影响和基因回路相互作用如何构成SZ病理生理学核心的神经振荡和连接异常的基础,为未来关于常见基因 - 神经功能相互作用以及针对SZ患者局部和全局网络水平神经功能障碍的潜在治疗干预的研究提供了一个框架。如将讨论的,许多影响SZ中神经振荡的这些基因也会影响其他神经系统疾病,从自闭症到癫痫。希望未来的研究能够及时揭示为什么相同的基因异常在一个人身上导致一种疾病,而在另一个人身上导致另一种疾病。