Faludi Gábor, Mirnics Károly
Department of Psychiatry, Kútvölgyi Clinical Centre, Semmelweis University, Budapest, Hungary.
Int J Dev Neurosci. 2011 May;29(3):305-9. doi: 10.1016/j.ijdevneu.2011.02.013. Epub 2011 Mar 5.
Clinical, epidemiological, neuroimaging and postmortem data all suggest schizophrenia is a neurodevelopmental disorder, and that synaptic disturbances might play a critical role in developing the disease. In 1982, Feinberg proposed that the schizophrenia might arise as a result of abnormal synaptic pruning. His hypothesis has survived 40years of accumulated data, and we review the critical findings related to synaptic dysfunction of schizophrenia. While it is clear that synaptic disturbances are integral and important for understanding the pathophysiology of schizophrenia, it has also become obvious that synaptic disturbances cannot be studied and understood as an independent disease hallmark, but only as a part of a complex network of homeostatic events. Development, glial-neural interaction, changes in energy homeostasis, diverse genetic predisposition, neuroimmune processes and environmental influences all can tip the delicate homeostatic balance of the synaptic morphology and connectivity in a uniquely individual fashion, thus contributing to the emergence of the various symptoms of this devastating disorder. Finally, we argue that based on a predominant change in gene expression pattern we can broadly sub-stratify schizophrenia into "synaptic" "oligodendroglial", "metabolic" and "inflammatory" subclasses.
临床、流行病学、神经影像学和尸检数据均表明，精神分裂症是一种神经发育障碍，且突触紊乱可能在该疾病的发生发展中起关键作用。1982年，费恩伯格提出精神分裂症可能是异常突触修剪的结果。他的假说历经40年积累的数据依然成立，我们回顾了与精神分裂症突触功能障碍相关的关键研究结果。虽然很明显突触紊乱对于理解精神分裂症的病理生理学不可或缺且至关重要，但同样明显的是，突触紊乱不能作为一种独立的疾病标志来研究和理解，而只能作为稳态事件复杂网络的一部分。发育、胶质-神经相互作用、能量稳态变化、多种遗传易感性、神经免疫过程和环境影响都可能以独特的个体方式打破突触形态和连接的微妙稳态平衡，从而导致这种毁灭性疾病的各种症状出现。最后，我们认为基于基因表达模式的主要变化，我们可以将精神分裂症大致细分为“突触型”“少突胶质细胞型”“代谢型”和“炎症型”亚类。
