重度抑郁症患者糖皮质激素受体基因(NR3C1)与认知的遗传和表观遗传变异。

0 PSYCHIATRY
Alex Ferrer, Javier Labad, Neus Salvat-Pujol, Mikel Urretavizcaya, Roser Obrador-Font, José M Menchón, Diego Palao, Carles Soriano-Mas, Javier Costas, Marta Barrachina, Ángel Carracedo, Virginia Soria
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引用次数: 0

摘要

许多研究发现,下丘脑-垂体-肾上腺(HPA)轴异常与重度抑郁症(MDD)的病理生理和认知功能有关。我们的目的是评估糖皮质激素受体(GR)基因NR3C1中三个不同启动子区域的遗传多态性和甲基化水平对重度抑郁症患者认知表现的影响。探讨了童年逆境的合理相互作用以及遗传和表观遗传变量之间的中介关系。材料与方法:64例重度抑郁症患者和82例健康对照。对所有参与者的童年虐待和神经认知表现进行评估。0.25 mg地塞米松给药后,采用地塞米松抑制试验分析HPA负反馈。对23个单核苷酸多态性进行了基因分型,并测量了GR基因外显子1D、1F和1H上几个CpGs的甲基化水平。结果:结果表明,在其他协变量的影响之外,NR3C1单核苷酸多态性和甲基化水平预测执行功能和工作记忆任务的表现。没有发现显著的相互作用或中介关系。结论:GR基因的遗传变异和表观遗传调控是影响重度抑郁症认知表现的相关因素,可能成为情绪障碍和其他应激相关障碍的重要生物标志物和治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Genetic and epigenetic changes to the glucocorticoid receptor gene (NR3C1) and cognition in major depressive disorder.

Introduction: Many studies have found that hypothalamic-pituitary-adrenal (HPA) axis abnormalities are related to the pathophysiology of major depressive disorder (MDD) and cognitive functioning. Our aim was to assess the influence of genetic polymorphisms and methylation levels in three different promoter regions throughout the glucocorticoid receptor (GR) gene NR3C1 on cognitive performance in MDD. Plausible interactions with childhood adversity and mediation relationships between genetic and epigenetic variables were explored.

Materials and methods: The sample included a total of 64 MDD patients and 82 healthy controls. Child maltreatment and neurocognitive performance were assessed in all participants. HPA negative feedback was analyzed using the dexamethasone suppression test after the administration of 0.25mg of dexamethasone. A total of 23 single-nucleotide polymorphisms were genotyped, and methylation levels at several CpGs in exons 1D, 1F and 1H of the GR gene were measured.

Results: Results show that, beyond the influence of other covariables, NR3C1 single-nucleotide polymorphisms and methylation levels predicted performance in executive functioning and working memory tasks. No significant interactions or mediation relationships were detected.

Conclusions: Results suggest that genetic variations and epigenetic regulation of the GR gene are relevant factors influencing cognitive performance in MDD and could emerge as significant biomarkers and therapeutic targets in mood disorders and other stress-related disorders.

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CiteScore
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