Effects of early life stress on biochemical indicators of the dopaminergic system: a meta-analysis of rodent studies

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 the MaDEapp, 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 causes a few yet robust changes on biochemical indicators of the dopaminergic system.

早期不良生活事件是导致多巴胺系统异常，如精神分裂症和成瘾等行为障碍确立的风险因素。早期生活状况与多巴胺系统的相关性已在超过90篇啮齿动物研究中进行因果探讨。本研究旨在验证早期生活压力（ELS）通过广泛的三级混合效应荟萃分析改变多巴胺信号传导的假设。我们纳入了多种ELS模型以及大脑不同区域的生化指标，共计1009个比较。与预期相反，仅有少数比较显示出显著效应。具体而言，纹状体区域最为脆弱，在ELS后表现出多巴胺前体减少和代谢物增加。为了使所有数据公开可及，我们创建了MaDEapp，这是一个用于探索荟萃分析数据的工具，旨在指导未来的（临床）研究并允许进行功效计算。总之，ELS在多巴胺系统生化指标上引起了一些虽不众多但稳健的变化。