Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center, Utrecht University, The Netherlands.
Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center, Utrecht University, The Netherlands; University Medical Center Groningen, University of Groningen, The Netherlands.
Neurosci Biobehav Rev. 2018 Dec;95:1-16. doi: 10.1016/j.neubiorev.2018.09.003. Epub 2018 Sep 7.
Adverse early life events are a well-established risk factor for the precipitation of behavioral disorders characterized by anomalies in the dopaminergic system, such as schizophrenia and addiction. The correlation between early life conditions and the dopaminergic system has been causally investigated in more than 90 rodent publications. Here, we tested the validity of the hypothesis that early life stress (ELS) alters dopamine signaling by performing an extensive 3-level mixed effect meta-analysis. We included several ELS models and biochemical indicators of the dopaminergic system in a variety of brain areas, for a total of 1009 comparisons. Contrary to our expectations, only a few comparisons displayed a significant effect. Specifically, the striatal area was the most vulnerable, displaying decreased dopamine precursor and increased metabolites after ELS. To make all data openly accessible, we created MaDEapp (https://osf.io/w25m4/), a tool to explore data of the meta-analysis with the intent to guide future (pre)clinical research and allow power calculations. All in all, ELS induces a few yet robust changes on biochemical indicators of the dopaminergic system.
不良的早期生活事件是导致多巴胺系统异常的行为障碍(如精神分裂症和成瘾)发生的一个既定风险因素。在 90 多篇啮齿动物研究中已经对早期生活条件与多巴胺系统之间的相关性进行了因果关系研究。在这里,我们通过进行广泛的 3 级混合效应荟萃分析来测试早期生活应激 (ELS) 是否会改变多巴胺信号的假设的有效性。我们在各种脑区中纳入了几种 ELS 模型和多巴胺系统的生化指标,总共进行了 1009 次比较。与我们的预期相反,只有少数比较显示出显著的效果。具体来说,纹状体区域最容易受到影响,在 ELS 后显示多巴胺前体减少和代谢物增加。为了使所有数据都公开可用,我们创建了 MaDEapp(https://osf.io/w25m4/),这是一种用于探索荟萃分析数据的工具,旨在指导未来的(临床前)研究并允许进行功效计算。总而言之,ELS 会导致多巴胺系统生化指标发生一些但却是强大的变化。