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儿童精神病理的遗传模式不同于成人且与胎儿小脑发育有关
作者:小柯机器人 发布时间:2023/5/28 22:03:40

美国马萨诸塞州总医院和哈佛医学院Joshua L. Roffman团队近期取得重要工作进展,他们研究发现儿童精神病理的遗传模式不同于成人且与胎儿小脑发育有关。相关研究成果2023年5月18日在线发表于《自然—神经科学》杂志上。

据介绍,儿童时期的精神症状通常是分散的,但在青春期晚期可能合并为离散的精神疾病。

研究人员利用多基因评分(PGS)来分析儿童症状的基因组风险,并利用转录组和神经成像数据揭示相关的神经发育机制。在独立样本(青少年大脑认知发展,R代)中,一种狭窄的交叉障碍神经发育PGS,反映了注意力缺陷多动障碍、自闭症、抑郁症和抽动秽语综合征的风险,预测青春期早期的精神症状,比广泛的交叉障碍PGS更敏感,反映了八种精神障碍的共同风险,单独的障碍特异性PGS或其他两种狭窄的交叉障碍(强迫、情绪-精神)评分。神经发育PGS相关基因优先在小脑中表达,其表达在产前达到峰值。

此外,小脑和功能耦合皮层区域的灰质体积较低与儿童中期的精神症状有关。

总之,这些发现表明,儿童精神症状的遗传基础与成人疾病的遗传基础不同,并暗示了胎儿小脑的发育过程将持续到儿童时期。

附:英文原文

Title: Genetic patterning for child psychopathology is distinct from that for adults and implicates fetal cerebellar development

Author: Hughes, Dylan E., Kunitoki, Keiko, Elyounssi, Safia, Luo, Mannan, Bazer, Oren M., Hopkinson, Casey E., Dowling, Kevin F., Doyle, Alysa E., Dunn, Erin C., Eryilmaz, Hamdi, Gilman, Jodi M., Holt, Daphne J., Valera, Eve M., Smoller, Jordan W., Cecil, Charlotte A. M., Tiemeier, Henning, Lee, Phil H., Roffman, Joshua L.

Issue&Volume: 2023-05-18

Abstract: Childhood psychiatric symptoms are often diffuse but can coalesce into discrete mental illnesses during late adolescence. We leveraged polygenic scores (PGSs) to parse genomic risk for childhood symptoms and to uncover related neurodevelopmental mechanisms with transcriptomic and neuroimaging data. In independent samples (Adolescent Brain Cognitive Development, Generation R) a narrow cross-disorder neurodevelopmental PGS, reflecting risk for attention deficit hyperactivity disorder, autism, depression and Tourette syndrome, predicted psychiatric symptoms through early adolescence with greater sensitivity than broad cross-disorder PGSs reflecting shared risk across eight psychiatric disorders, the disorder-specific PGS individually or two other narrow cross-disorder (Compulsive, Mood-Psychotic) scores. Neurodevelopmental PGS-associated genes were preferentially expressed in the cerebellum, where their expression peaked prenatally. Further, lower gray matter volumes in cerebellum and functionally coupled cortical regions associated with psychiatric symptoms in mid-childhood. These findings demonstrate that the genetic underpinnings of pediatric psychiatric symptoms differ from those of adult illness, and implicate fetal cerebellar developmental processes that endure through childhood.

DOI: 10.1038/s41593-023-01321-8

Source: https://www.nature.com/articles/s41593-023-01321-8

期刊信息

Nature Neuroscience:《自然—神经科学》,创刊于1998年。隶属于施普林格·自然出版集团,最新IF:28.771
官方网址:https://www.nature.com/neuro/
投稿链接:https://mts-nn.nature.com/cgi-bin/main.plex