Chromosomes in eukaryotic cell nuclei are highly compacted and finely organized into hierarchical three-dimensional (3D) configuration. In recent years, scientists have gained deeper understandings of 3D genome structures and revealed novel evidence linking 3D genome organization to various important cell events on the molecular level. Most importantly, alteration of 3D genome architecture has emerged as an intriguing higher order mechanism that connects disease-related genetic variants in multiple heterogenous and polygenic neuropsychological disorders, delivering novel insights into the etiology. In this review, we provide a brief overview of the hierarchical structures of 3D genome and two proposed regulatory models, loop extrusion and phase separation. We then focus on recent Hi-C data in the central nervous system and discuss 3D genome alterations during normal brain development and in mature neurons. Most importantly, we make a comprehensive review on current knowledge and discuss the role of 3D genome in multiple neuropsychological disorders, including schizophrenia, repeat expansion disorders, 22q11 deletion syndrome, and others.

真核细胞核中的染色体高度压缩并精细地组织成分层的三维 (3D) 配置。近年来，科学家们对 3D 基因组结构有了更深入的了解，并揭示了将 3D基因组组织联系起来的新证据分子水平上的各种重要细胞事件。最重要的是，3D 基因组结构的改变已成为一种有趣的高阶机制，它将多种异源性和多基因神经心理疾病中与疾病相关的遗传变异联系起来，为病因学提供了新的见解。在这篇综述中，我们简要概述了 3D 基因组的层次结构和两个提出的调控模型，即环挤压和相分离。然后，我们关注中枢神经系统中最近的 Hi-C 数据，并讨论正常大脑发育和成熟神经元中的 3D 基因组改变。最重要的是，我们对现有知识进行了全面回顾，并讨论了 3D 基因组在多种神经心理疾病中的作用，包括精神分裂症、重复扩张障碍、