Previous neuroimaging research has established associations between urban exposure during early life and alterations in brain function and structure. However, the molecular mechanisms and behavioral relevance of these associations remain largely unknown. Here, we aimed to address this question using a combined analysis of multimodal data. Initially, we calculated amplitude of low-frequency fluctuations (ALFF) and gray matter volume (GMV) using resting-state functional and structural MRI to investigate their associations with early-life urbanization in a large sample of 511 healthy young adults. Then, we examined the spatial relationships of the identified neural correlates of early-life urbanization with gene expression, neurotransmitter, and behavioral domain atlases. Results showed that higher early-life urbanization scores were correlated with increased ALFF of the right fusiform gyrus and decreased GMV of the left dorsal medial prefrontal cortex and left precuneus. Remarkably, the identified neural correlates of early-life urbanization were spatially correlated with expression of gene categories primarily involving immune system process, signal transduction, and cellular metabolic process. Concurrently, there were significant associations between the neural correlates and specific neurotransmitter systems including dopamine, acetylcholine, and serotonin. Finally, we found that the ALFF correlates were associated with behavioral terms including “perception,” “sensory,” “cognitive control,” and “reasoning.” Apart from expanding existing knowledge of early-life urban environmental risk for mental disorders and health in general, our findings may contribute to an emerging framework for integrating social science, neuroscience, genetics, and public policy to respond to the major health challenge of world urbanization.

先前的神经影像学研究已经建立了早年城市暴露与大脑功能和结构改变之间的联系。然而，这些关联的分子机制和行为相关性仍然很大程度上未知。在这里，我们旨在通过多模态数据的组合分析来解决这个问题。最初，我们使用静息态功能和结构 MRI 计算了低频波动 (ALFF) 和灰质体积 (GMV) 的幅度，以调查 511 名健康年轻人的大样本中它们与早期城市化的关系。然后，我们检查了已识别的早期城市化神经关联与基因表达、神经递质和行为领域图谱的空间关系。结果显示，较高的早期城市化分数与右侧梭状回的 ALFF 增加以及左侧背内侧前额叶皮层和左侧楔前叶的 GMV 降低相关。值得注意的是，已确定的早期城市化的神经相关性与主要涉及免疫系统过程、信号转导和细胞代谢过程的基因类别的表达在空间上相关。同时，神经相关物与特定神经递质系统（包括多巴胺、乙酰胆碱和血清素）之间存在显着关联。最后，我们发现 ALFF 相关性与行为术语相关，包括“感知”、“感觉”、“认知控制”和“推理”。“除了扩大对早期城市环境对精神障碍和健康的风险的现有认识外，我们的研究结果可能有助于建立一个新兴框架，整合社会科学、神经科学、遗传学和公共政策，以应对世界面临的重大健康挑战城市化。