Adrian Dahl Askelund, Laura Hegemann, Andrea G Allegrini, Elizabeth C Corfield, Helga Ask, Neil M Davies, Ole A Andreassen, Alexandra Havdahl, Laurie J Hannigan
{"title":"早期生活中区分行为和情绪问题的基因结构。","authors":"Adrian Dahl Askelund, Laura Hegemann, Andrea G Allegrini, Elizabeth C Corfield, Helga Ask, Neil M Davies, Ole A Andreassen, Alexandra Havdahl, Laurie J Hannigan","doi":"10.1016/j.biopsych.2024.12.021","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Early in life, behavioral and cognitive traits associated with risk for developing a psychiatric condition are broad and undifferentiated. As children develop, these traits differentiate into characteristic clusters of symptoms and behaviors that ultimately form the basis of diagnostic categories. Understanding this differentiation process - in the context of genetic risk for psychiatric conditions, which is highly generalized - can improve early detection and intervention.</p><p><strong>Methods: </strong>We modeled the differentiation of behavioral and emotional problems from age 1.5-5 years (behavioral problems - emotional problems = differentiation score) in a pre-registered study of ∼79,000 children from the population-based Norwegian Mother, Father, and Child Cohort Study. We used genomic structural equation modeling to identify genetic signal in differentiation and total problems, investigating their links with 11 psychiatric and neurodevelopmental conditions. We examined associations of polygenic scores (PGS) with both outcomes and assessed the relative contributions of direct and indirect genetic effects in ∼33,000 family trios.</p><p><strong>Results: </strong>Differentiation was primarily genetically correlated with psychiatric conditions via a \"neurodevelopmental\" factor. Total problems were primarily associated with the \"neurodevelopmental\" factor and \"p\"-factor. PGS analyses revealed an association between liability to ADHD and differentiation (β=0.11 [0.10,0.12]), and a weaker association with total problems (β=0.06 [0.04,0.07]). Trio-PGS analyses showed predominantly direct genetic effects on both outcomes.</p><p><strong>Conclusions: </strong>We uncovered genomic signal in the differentiation process, mostly related to common variants associated with neurodevelopmental conditions. Investigating the differentiation of early life behavioral and emotional problems may enhance our understanding of the developmental emergence of different psychiatric and neurodevelopmental conditions.</p>","PeriodicalId":8918,"journal":{"name":"Biological Psychiatry","volume":" ","pages":""},"PeriodicalIF":9.6000,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The genetic architecture of differentiating behavioral and emotional problems in early life.\",\"authors\":\"Adrian Dahl Askelund, Laura Hegemann, Andrea G Allegrini, Elizabeth C Corfield, Helga Ask, Neil M Davies, Ole A Andreassen, Alexandra Havdahl, Laurie J Hannigan\",\"doi\":\"10.1016/j.biopsych.2024.12.021\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Early in life, behavioral and cognitive traits associated with risk for developing a psychiatric condition are broad and undifferentiated. As children develop, these traits differentiate into characteristic clusters of symptoms and behaviors that ultimately form the basis of diagnostic categories. Understanding this differentiation process - in the context of genetic risk for psychiatric conditions, which is highly generalized - can improve early detection and intervention.</p><p><strong>Methods: </strong>We modeled the differentiation of behavioral and emotional problems from age 1.5-5 years (behavioral problems - emotional problems = differentiation score) in a pre-registered study of ∼79,000 children from the population-based Norwegian Mother, Father, and Child Cohort Study. We used genomic structural equation modeling to identify genetic signal in differentiation and total problems, investigating their links with 11 psychiatric and neurodevelopmental conditions. We examined associations of polygenic scores (PGS) with both outcomes and assessed the relative contributions of direct and indirect genetic effects in ∼33,000 family trios.</p><p><strong>Results: </strong>Differentiation was primarily genetically correlated with psychiatric conditions via a \\\"neurodevelopmental\\\" factor. Total problems were primarily associated with the \\\"neurodevelopmental\\\" factor and \\\"p\\\"-factor. PGS analyses revealed an association between liability to ADHD and differentiation (β=0.11 [0.10,0.12]), and a weaker association with total problems (β=0.06 [0.04,0.07]). Trio-PGS analyses showed predominantly direct genetic effects on both outcomes.</p><p><strong>Conclusions: </strong>We uncovered genomic signal in the differentiation process, mostly related to common variants associated with neurodevelopmental conditions. Investigating the differentiation of early life behavioral and emotional problems may enhance our understanding of the developmental emergence of different psychiatric and neurodevelopmental conditions.</p>\",\"PeriodicalId\":8918,\"journal\":{\"name\":\"Biological Psychiatry\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":9.6000,\"publicationDate\":\"2025-01-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biological Psychiatry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.biopsych.2024.12.021\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biological Psychiatry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.biopsych.2024.12.021","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
The genetic architecture of differentiating behavioral and emotional problems in early life.
Background: Early in life, behavioral and cognitive traits associated with risk for developing a psychiatric condition are broad and undifferentiated. As children develop, these traits differentiate into characteristic clusters of symptoms and behaviors that ultimately form the basis of diagnostic categories. Understanding this differentiation process - in the context of genetic risk for psychiatric conditions, which is highly generalized - can improve early detection and intervention.
Methods: We modeled the differentiation of behavioral and emotional problems from age 1.5-5 years (behavioral problems - emotional problems = differentiation score) in a pre-registered study of ∼79,000 children from the population-based Norwegian Mother, Father, and Child Cohort Study. We used genomic structural equation modeling to identify genetic signal in differentiation and total problems, investigating their links with 11 psychiatric and neurodevelopmental conditions. We examined associations of polygenic scores (PGS) with both outcomes and assessed the relative contributions of direct and indirect genetic effects in ∼33,000 family trios.
Results: Differentiation was primarily genetically correlated with psychiatric conditions via a "neurodevelopmental" factor. Total problems were primarily associated with the "neurodevelopmental" factor and "p"-factor. PGS analyses revealed an association between liability to ADHD and differentiation (β=0.11 [0.10,0.12]), and a weaker association with total problems (β=0.06 [0.04,0.07]). Trio-PGS analyses showed predominantly direct genetic effects on both outcomes.
Conclusions: We uncovered genomic signal in the differentiation process, mostly related to common variants associated with neurodevelopmental conditions. Investigating the differentiation of early life behavioral and emotional problems may enhance our understanding of the developmental emergence of different psychiatric and neurodevelopmental conditions.
期刊介绍：
Biological Psychiatry is an official journal of the Society of Biological Psychiatry and was established in 1969. It is the first journal in the Biological Psychiatry family, which also includes Biological Psychiatry: Cognitive Neuroscience and Neuroimaging and Biological Psychiatry: Global Open Science. The Society's main goal is to promote excellence in scientific research and education in the fields related to the nature, causes, mechanisms, and treatments of disorders pertaining to thought, emotion, and behavior. To fulfill this mission, Biological Psychiatry publishes peer-reviewed, rapid-publication articles that present new findings from original basic, translational, and clinical mechanistic research, ultimately advancing our understanding of psychiatric disorders and their treatment. The journal also encourages the submission of reviews and commentaries on current research and topics of interest.
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