Askelund Adrian Dahl, Hegemann Laura, Allegrini Andrea G, Corfield Elizabeth C, Ask Helga, Davies Neil M, Andreassen Ole A, Havdahl Alexandra, Hannigan Laurie J
PsychGen Center for Genetic Epidemiology and Mental Health, Norwegian Institute of Public Health, Oslo, Norway; Psychiatric Genetic Epidemiology Group, Research Department, Lovisenberg Diaconal Hospital, Oslo, Norway.
PsychGen Center for Genetic Epidemiology and Mental Health, Norwegian Institute of Public Health, Oslo, Norway; Psychiatric Genetic Epidemiology Group, Research Department, Lovisenberg Diaconal Hospital, Oslo, Norway.
Biol Psychiatry. 2025 Jun 15;97(12):1163-1174. doi: 10.1016/j.biopsych.2024.12.021. Epub 2025 Jan 9.
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.
We modeled the differentiation of behavioral and emotional problems from age 1.5 to 5 years (behavioral problems - emotional problems = differentiation score) in a preregistered 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.
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 attention-deficit/hyperactivity disorder and differentiation (β = 0.11; 95% CI, 0.10 to 0.12) and a weaker association with total problems (β = 0.06; 95% CI, 0.04 to 0.07). Trio-PGS analyses showed predominantly direct genetic effects on both outcomes.
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.
在生命早期，与患精神疾病风险相关的行为和认知特征广泛且无差异。随着儿童成长，这些特征分化为症状和行为的特征性集群，最终构成诊断类别的基础。在精神疾病遗传风险高度普遍的背景下理解这一分化过程，可改善早期检测和干预。
在一项对约79000名来自挪威基于人群的母婴和儿童队列研究的儿童进行的预注册研究中，我们模拟了1.5岁至5岁期间行为和情绪问题的分化（行为问题 - 情绪问题 = 分化分数）。我们使用基因组结构方程模型来识别分化和总问题中的遗传信号，研究它们与11种精神和神经发育疾病的联系。我们检查了多基因评分（PGS）与这两个结果的关联，并评估了约33000个家庭三人组中直接和间接遗传效应的相对贡献。
分化主要通过神经发育因素与精神疾病存在遗传相关性。总问题主要与神经发育因素和p因素相关。PGS分析显示注意力缺陷多动障碍易感性与分化之间存在关联（β = 0.11；95%置信区间，0.10至0.12），与总问题的关联较弱（β = 0.06；95%置信区间，0.04至0.07）。三人组PGS分析显示对这两个结果主要有直接遗传效应。
我们在分化过程中发现了基因组信号，主要与与神经发育疾病相关的常见变异有关。研究生命早期行为和情绪问题的分化可能会增强我们对不同精神和神经发育疾病发展出现的理解。
