Molecular substrates of schizophrenia: homeostatic signaling to connectivity.
Molecular substrates of schizophrenia: homeostatic signaling to connectivity.
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DOI：
10.1038/mp.2015.141
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发表时间：
2016-01
影响因子：
11
通讯作者：
Sawa A
中科院分区：
文献类型：
--
作者：
Landek-Salgado MA;Faust TE;Sawa A
精神分裂症（SZ）是一种破坏性的精神疾病，影响许多大脑系统。最近的研究已经确定了遗传因素，赋予SZ的风险增加，并参与疾病的发病机制。与这种自下而上的方法平行，其他研究通过脑成像、神经化学和药理学方法广泛报道了患者的生物学变化。这篇综述强调了通过SZ患者的研究，即那些使用自上而下的方法确定的分子底物，同时也提到了最近的遗传学研究的丰硕成果。我们已经按系统对分子底物进行了细分，重点是神经传递的元素、与白色物质相关的连接中的靶点、免疫/炎症和氧化应激相关的底物以及内分泌和代谢级联中的分子。我们进一步触及这些系统之间的串扰和评论的效用，动物模型在绘制这些基板的发展进程和相互作用。基于这一全面的信息，我们提出了一个框架，SZ研究的基础上的一个不平衡的假设，稳态信号从免疫/炎症，氧化应激，内分泌和代谢级联反应，至少在一定程度上，在神经连接相关SZ的基础赤字。因此，本次审查的目的是提供信息，是有益的补充，致病性的假设，已经出现了遗传学研究。基于SZ研究的这些进展，我们高度期望发现可能有助于SZ早期干预、诊断或治疗的生物标志物。
Schizophrenia (SZ) is a devastating psychiatric condition affecting numerous brain systems. Recent studies have identified genetic factors that confer an increased risk of SZ and participate in the disease etiopathogenesis. In parallel to such bottom-up approaches, other studies have extensively reported biological changes in patients by brain imaging, neurochemical and pharmacological approaches. This review highlights the molecular substrates identified through studies with SZ patients, namely those using top-down approaches, while also referring to the fruitful outcomes of recent genetic studies. We have sub-classified the molecular substrates by system, focusing on elements of neurotransmission, targets in white matter-associated connectivity, immune/inflammatory and oxidative stress-related substrates, and molecules in endocrine and metabolic cascades. We further touch on crosstalk among these systems and comment on the utility of animal models in charting the developmental progression and interaction of these substrates. Based on this comprehensive information, we propose a framework for SZ research based on the hypothesis of an imbalance in homeostatic signaling from immune/inflammatory, oxidative stress, endocrine and metabolic cascades that, at least in part, underlies deficits in neural connectivity relevant to SZ. Thus, this review aims to provide information that is translationally useful and complementary to pathogenic hypotheses that have emerged from genetic studies. Based on such advances in SZ research, it is highly expected that we will discover biomarkers that may help in the early intervention, diagnosis or treatment of SZ.