Peripheral DNA Methylation of Cortisol- and Serotonin-Related Genes Predicts Hippocampal Volume in a Pediatric Population

IF 4 Q2 NEUROSCIENCES

Biological psychiatry global open science Pub Date : 2024-11-26 DOI:10.1016/j.bpsgos.2024.100421

Taena Hanson , Sophia Spencer , Samantha A. Harker , Fatoumata Barry , Phoebe Burton , Jennifer Beauchemin , Sarah E. Mennenga , B. Blair Braden , Viren D'Sa , Daphne Koinis-Mitchell , Sean C.L. Deoni , Candace R. Lewis

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Abstract

Background

Hippocampal volume increases throughout early development and is an important indicator of cognitive abilities and mental health. However, hippocampal development is highly vulnerable to exposures during development, as seen by smaller hippocampal volume and differential epigenetic programming in genes implicated in mental health. However, few studies have investigated hippocampal volume in relation to the peripheral epigenome across development, and even less is known about potential genetic moderators. Therefore, in this study, we explored relationships between hippocampal volume and peripheral DNA methylation of mental health–related genes, specifically NR3C1, FKBP5, and SLC6A4, throughout early development and whether these associations were moderated by age or genotype.

Methods

Bilateral hippocampal volume was computed from T2-weighted images through FreeSurfer, and DNA methylation was measured from saliva using the Illumina MethylationEPIC microarray in a pediatric population (N = 248, females = 112, mean_age = 5.13 years, SD_age = 3.60 years).

Results

Multiple linear regression and bootstrapping analyses revealed that DNA methylation of NR3C1, FKBP5, and SLC6A4 was associated with hippocampal volume and that these relationships were moderated by age and gene-specific variants.

Conclusions

These findings support the validity of peripheral DNA methylation profiles for indirectly assessing hippocampal volume and development and underscore the importance of genotype and age considerations in research. Therefore, peripheral epigenetic profiles may be a promising avenue for investigating the impacts of early-life stress on brain structure and subsequent mental health outcomes.

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皮质醇和血清素相关基因的外周DNA甲基化预测儿童海马体积

背景：海马体积在早期发育过程中增加，是认知能力和心理健康的重要指标。然而，海马体的发育在发育过程中极易受到暴露的影响，这可以从较小的海马体体积和与心理健康有关的基因的差异表观遗传编程中看出。然而，很少有研究调查海马体积在整个发育过程中与外周表观基因组的关系，对潜在的遗传调节因子的了解就更少了。因此，在本研究中，我们探索了海马体体积与心理健康相关基因（特别是NR3C1、FKBP5和SLC6A4）外周DNA甲基化在早期发育过程中的关系，以及这些关联是否会因年龄或基因型而减弱。方法：通过FreeSurfer通过t2加权图像计算双侧海马体积，并使用Illumina MethylationEPIC芯片从儿童人群（N = 248，女性= 112，平均年龄= 5.13岁，年龄= 3.60岁）的唾液中测量DNA甲基化。结果：多元线性回归和bootstrapping分析显示，NR3C1、FKBP5和SLC6A4的DNA甲基化与海马体积相关，这些关系受到年龄和基因特异性变异的调节。结论：这些发现支持了外周DNA甲基化谱间接评估海马体积和发育的有效性，并强调了基因型和年龄因素在研究中的重要性。因此，外周表观遗传谱可能是研究早期生活压力对大脑结构和随后的心理健康结果的影响的一个有希望的途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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