Genetic patterning for child psychopathology is distinct from that for adults and implicates fetal cerebellar development.
Genetic patterning for child psychopathology is distinct from that for adults and implicates fetal cerebellar development.
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DOI：
10.1038/s41593-023-01321-8
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发表时间：
2023-06
影响因子：
25
通讯作者：
Roffman JL
中科院分区：
文献类型：
--
作者：
Hughes DE;Kunitoki K;Elyounssi S;Luo M;Bazer OM;Hopkinson CE;Dowling KF;Doyle AE;Dunn EC;Eryilmaz H;Gilman JM;Holt DJ;Valera EM;Smoller JW;Cecil CAM;Tiemeier H;Lee PH;Roffman JL
儿童期的精神症状通常是弥漫性的，但在青春期后期可能合并成离散的精神疾病。我们利用多基因评分（PGS）来分析儿童症状的基因组风险，并利用转录组学和神经影像学数据揭示相关的神经发育机制。在独立样本中（青少年脑认知发展，R代）一个狭窄的交叉障碍神经发育PGS，反映了注意缺陷多动障碍，自闭症，抑郁症和图雷特综合征的风险，预测精神症状，通过青春期早期的敏感性高于广泛的交叉障碍PGS，反映了八种精神疾病的共同风险，单独的疾病特异性PGS或两个其他狭窄的交叉疾病（强迫症，情绪精神病）评分。神经发育PGS-associated基因优先表达在小脑，他们的表达在产前达到高峰。此外，小脑和功能耦合皮质区域的灰质体积较低与儿童中期的精神症状相关。这些研究结果表明，儿童精神病症状的遗传基础不同于成人疾病，并涉及胎儿小脑发育过程，持续到童年。
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.
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影响因子：
11
作者：
International Obsessive Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and OCD Collaborative Genetics Association Studies (OCGAS)
通讯作者：
International Obsessive Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and OCD Collaborative Genetics Association Studies (OCGAS)
影响因子：
5.7
作者：
Diedrichsen, Joern;Balsters, Joshua H.;Ramnani, Narender
通讯作者：
Ramnani, Narender
影响因子：
9.2
作者：
Choi, Shing Wan;O'Reilly, Paul F.
通讯作者：
O'Reilly, Paul F.
影响因子：
4.7
作者：
Casey BJ;Cannonier T;Conley MI;Cohen AO;Barch DM;Heitzeg MM;Soules ME;Teslovich T;Dellarco DV;Garavan H;Orr CA;Wager TD;Banich MT;Speer NK;Sutherland MT;Riedel MC;Dick AS;Bjork JM;Thomas KM;Chaarani B;Mejia MH;Hagler DJ Jr;Daniela Cornejo M;Sicat CS;Harms MP;Dosenbach NUF;Rosenberg M;Earl E;Bartsch H;Watts R;Polimeni JR;Kuperman JM;Fair DA;Dale AM;ABCD Imaging Acquisition Workgroup
通讯作者：
ABCD Imaging Acquisition Workgroup
影响因子：
5.7
作者：
Dale, AM;Fischl, B;Sereno, MI
通讯作者：
Sereno, MI