FIDMAG Germanes Hospitalàries Research Foundation, 08830 Sant Boi de Llobregat, Barcelona, Spain.
CIBERSAM (Biomedical Research Network in Mental Health, Instituto de Salud Carlos III), 28029 Madrid, Madrid, Spain.
Int J Mol Sci. 2023 Feb 10;24(4):3597. doi: 10.3390/ijms24043597.
Schizophrenia is a psychiatric disorder that results from genetic and environmental factors interacting and disrupting neurodevelopmental trajectories. Human Accelerated Regions (HARs) are evolutionarily conserved genomic regions that have accumulated human-specific sequence changes. Thus, studies on the impact of HARs in the context of neurodevelopment, as well as with respect to adult brain phenotypes, have increased considerably in the last few years. Through a systematic approach, we aim to offer a comprehensive review of HARs' role in terms of human brain development, configuration, and cognitive abilities, as well as whether HARs modulate the susceptibility to neurodevelopmental psychiatric disorders such as schizophrenia. First, the evidence in this review highlights HARs' molecular functions in the context of the neurodevelopmental regulatory genetic machinery. Second, brain phenotypic analyses indicate that HAR genes' expression spatially correlates with the regions that suffered human-specific cortical expansion, as well as with the regional interactions for synergistic information processing. Lastly, studies based on candidate HAR genes and the global "HARome" variability describe the involvement of these regions in the genetic background of schizophrenia, but also in other neurodevelopmental psychiatric disorders. Overall, the data considered in this review emphasise the crucial role of HARs in human-specific neurodevelopment processes and encourage future research on this evolutionary marker for a better understanding of the genetic basis of schizophrenia and other neurodevelopmental-related psychiatric disorders. Accordingly, HARs emerge as interesting genomic regions that require further study in order to bridge the neurodevelopmental and evolutionary hypotheses in schizophrenia and other related disorders and phenotypes.
精神分裂症是一种由遗传和环境因素相互作用和破坏神经发育轨迹而导致的精神障碍。人类加速区（HARs）是进化上保守的基因组区域，积累了人类特异性的序列变化。因此，近年来，关于 HARs 在神经发育背景下以及在成年大脑表型方面的影响的研究有了相当大的增加。通过系统的方法，我们旨在全面综述 HARs 在人类大脑发育、结构和认知能力方面的作用，以及 HARs 是否调节精神分裂症等神经发育性精神障碍的易感性。首先，本综述中的证据强调了 HARs 在神经发育调控遗传机制背景下的分子功能。其次，大脑表型分析表明，HAR 基因的表达与经历人类特异性皮层扩张的区域以及协同信息处理的区域相互作用具有空间相关性。最后，基于候选 HAR 基因和全球“HARome”变异性的研究描述了这些区域在精神分裂症遗传背景中的参与，以及在其他神经发育性精神障碍中的参与。总的来说，本综述中考虑的数据强调了 HARs 在人类特异性神经发育过程中的关键作用，并鼓励对这一进化标记进行进一步研究，以更好地理解精神分裂症和其他神经发育相关精神障碍的遗传基础。因此，HARs 作为有趣的基因组区域出现，需要进一步研究，以弥合精神分裂症和其他相关障碍和表型中的神经发育和进化假说。
