Wang Hee-Hwan, Moon Seo-Yoon, Kim Hyeonjin, Kim Gakyung, Ahn Woo-Young, Joo Yoonjung Yoonie, Cha Jiook
Department of Brain Cognitive and Science, Seoul National University, Seoul, 08825, South Korea.
College of Liberal Studies, Seoul National University, Seoul, 08825, South Korea.
Heliyon. 2023 Dec 9;10(1):e23345. doi: 10.1016/j.heliyon.2023.e23345. eCollection 2024 Jan 15.
The enduring influence of early life stress (ELS) on brain and cognitive development has been widely acknowledged, yet the precise mechanisms underlying this association remain elusive. We hypothesize that ELS might disrupt the genome-wide influence on brain morphology and connectivity development, consequently exerting a detrimental impact on children's cognitive ability. We analyzed the multimodal data of DNA genotypes, brain imaging (structural and diffusion MRI), and neurocognitive battery (NIH Toolbox) of 4276 children (ages 9-10 years, European ancestry) from the Adolescent Brain Cognitive Development (ABCD) study. The genome-wide influence on cognitive function was estimated using the polygenic score (GPS). By using brain morphometry and tractography, we identified the brain correlates of the cognition GPSs. Statistical analyses revealed relationships for the gene-brain-cognition pathway. The brain structural variance significantly mediated the genetic influence on cognition (indirect effect = 0.016, P < 0.001). Of note, this gene-brain relationship was significantly modulated by abuse, resulting in diminished cognitive capacity (Index of Moderated Mediation = -0.007; 95 % CI = -0.012 ∼ -0.002). Our results support a novel gene-brain-cognition model likely elucidating the long-lasting negative impact of ELS on children's cognitive development.
早年生活应激（ELS）对大脑和认知发展的持久影响已得到广泛认可，但其背后的确切机制仍不清楚。我们假设，ELS可能会破坏全基因组对大脑形态和连接发育的影响，从而对儿童的认知能力产生不利影响。我们分析了来自青少年大脑认知发展（ABCD）研究的4276名儿童（9至10岁，欧洲血统）的DNA基因型、脑成像（结构和扩散MRI）和神经认知测试组合（美国国立卫生研究院工具箱）的多模态数据。使用多基因评分（GPS）估计全基因组对认知功能的影响。通过脑形态测量和纤维束成像，我们确定了认知GPS的大脑相关因素。统计分析揭示了基因-大脑-认知途径之间的关系。脑结构变异显著介导了基因对认知的影响（间接效应=0.016，P<0.001）。值得注意的是，这种基因与大脑的关系受到虐待的显著调节，导致认知能力下降（调节中介指数=-0.007；95%CI=-0.012至-0.002）。我们的结果支持了一种新的基因-大脑-认知模型，该模型可能阐明了ELS对儿童认知发展的长期负面影响。
