Allostatic load in early adolescence: gene / environment contributions and relevance for mental health.
Allostatic load in early adolescence: gene / environment contributions and relevance for mental health.
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青春期早期的稳态负荷：基因/环境的贡献以及与心理健康的相关性。
DOI：
10.1101/2023.10.27.23297674
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Barzilay,Ran
中科院分区：
文献类型：
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作者：
Hoffman,KevinW;Tran,KateT;Moore,TylerM;Gataviņš,MārtiņšM;Visoki,Elina;DiDomenico,GraceE;Schultz,LauraM;Almasy,Laura;Hayes,MatthewR;Daskalakis,NikolaosP;Barzilay,Ran
背景：适应负荷是由于长期逆境对身体造成的累积“磨损”。我们的目的是测试多环境（暴露体）和多基因对适应负荷的贡献，以及它们对早期青少年心理健康的综合贡献。方法我们分析了来自青少年大脑认知发展研究（ABCD）的N = 5035名不同类型的青少年（平均年龄12岁）的数据。采用降维方法，我们计算了身体质量指数（BMI）、腰围、血压、血糖、血胆固醇和唾液脱氢表雄酮（DHEA）的总适应负荷评分（AL）。使用11岁前的多层次环境暴露来量化儿童暴露风险。采用代谢系统易感性（2型糖尿病[T2D]）和应激相关精神疾病（重度抑郁症[MDD]）的多基因风险评分（PRS）对遗传风险进行量化。我们使用线性混合效应模型来检验暴露体和多基因风险（自变量）对AL（因变量）的主要、附加和交互影响。中介模型检验了AL在暴露体和多基因风险对青少年心理健康的通路中的中介作用。根据人口统计学和遗传主成分调整的模型。结果：与西班牙裔和非西班牙裔黑人青年相比，我们观察到非西班牙裔白人青年AL显著降低的差异。在不同的样本中，儿童暴露负荷与青春期AL相关（β =0.25, 95%CI 0.22-0.29， P< 0.001）。在欧洲血统的参与者中（n= 2928）， T2D和抑郁症的多基因风险与AL相关（T2D- prs β =0.11, 95%CI 0.07-0.14， P< 0.001; MDD-PRS β =0.05, 95%CI 0.02-0.09， P= 0.003）。两种多基因评分都显示了与暴露体风险的显著相互作用，因此，多基因风险越大，暴露体与AL之间的关联就越强。AL部分介导暴露风险和MDD-PRS对青少年心理健康的影响，完全介导T2D-PRS对青少年心理健康的影响。结论可以通过人体测量和生物学测量对青少年进行量化，并绘制暴露和多基因风险图。主要和相互作用的环境和遗传效应支持素质-应激模型。研究结果表明，在模拟与压力相关的健康状况时，环境和遗传风险都要考虑在内。
BackgroundAllostatic load is the cumulative “wear and tear” on the body due to chronic adversity. We aimed to test poly-environmental (exposomic) and polygenic contributions to allostatic load and their combined contribution to early adolescent mental health.MethodsWe analyzed data on N = 5,035 diverse youth (mean age 12) from the Adolescent Brain Cognitive Development Study (ABCD). Using dimensionality reduction method, we calculated and overall allostatic load score (AL) using body mass index [BMI], waist circumference, blood pressure, blood glycemia, blood cholesterol, and salivary DHEA. Childhood exposomic risk was quantified using multi-level environmental exposures before age 11. Genetic risk was quantified using polygenic risk scores (PRS) for metabolic system susceptibility (type 2 diabetes [T2D]) and stress-related psychiatric disease (major depressive disorder [MDD]). We used linear mixed effects models to test main, additive, and interactive effects of exposomic and polygenic risk (independent variables) on AL (dependent variable). Mediation models tested the mediating role of AL on the pathway from exposomic and polygenic risk to youth mental health. Models adjusted for demographics and genetic principal components.ResultsWe observed disparities in AL with non-Hispanic White youth having significantly lower AL compared to Hispanic and Non-Hispanic Black youth. In the diverse sample, childhood exposomic burden was associated with AL in adolescence (beta=0.25, 95%CI 0.22–0.29, P<.001). In European ancestry participants (n=2,928), polygenic risk of both T2D and depression was associated with AL (T2D-PRS beta=0.11, 95%CI 0.07–0.14, P<.001; MDD-PRS beta=0.05, 95%CI 0.02–0.09, P=.003). Both polygenic scores showed significant interaction with exposomic risk such that, with greater polygenic risk, the association between exposome and AL was stronger. AL partly mediated the pathway to youth mental health from exposomic risk and from MDD-PRS, and fully mediated the pathway from T2D-PRS.ConclusionsAL can be quantified in youth using anthropometric and biological measures and is mapped to exposomic and polygenic risk. Main and interactive environmental and genetic effects support a diathesis-stress model. Findings suggest that both environmental and genetic risk be considered when modeling stress-related health conditions.