功能性多基因风险评分的糖皮质激素依赖的调节元件活动及其与临床和压力相关的表型的关系
F Linsen1, P C Habets2, Y Milaneschi3
1Department of Psychiatry and Anatomy & Neurosciences, Amsterdam University Medical Center location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Amsterdam Public Health, Mental Health Program and Amsterdam Neuroscience, Mood, Anxiety, Psychosis, Sleep & Stress Program, Amsterdam, the Netherlands.
Psychoneuroendocrinology
|November 30, 2025
概括
这项研究探讨了遗传风险得分与与压力有关的疾病之间的联系. 虽然与诊断无关,但DEX功能性多基因风险评分 (fPRS) 可能会影响HPA轴的敏感性和抑郁和焦虑的发作复发.
科学领域:
- 精神病学遗传学 精神病学遗传学
- 与压力相关的疾病
- 葡萄糖皮质体受体信号传递
背景情况:
- 慢性压力和不良生活事件是导致抑郁和焦虑障碍的关键因素.
- 影响葡萄糖皮质激素 (GC) 反应的遗传变异可能会改变压力对精神健康的影响.
- 基于GC响应元素 (DEX-fPRS) 的功能性多基因风险评分 (fPRS) 已被开发来评估这种联系.
研究的目的:
- 调查DEX-fPRS与与临床/生物压力相关的表型之间的关联.
- 检查基因变异在GC激素反应中的作用,以缓解压力对心理健康的影响.
- 评估与抑郁症/焦虑症诊断的关联,症状严重程度和HPA轴活动.
主要方法:
- 分析了2286名来自荷兰NESDA队列的参与者,并提供了纵向数据.
- 回归模型测试了DEX-fPRS与终身诊断,症状严重程度和皮质醇水平之间的关联.
- 用于验证的是对照得分 (VEH-fPRS) 和MARS队列中的复制.
主要成果:
- DEX-fPRS没有显示与终身诊断或纠正后症状严重程度的显著关联.
- 标称关联表明DEX-fPRS和HPA轴敏感性 (皮质醇水平) 之间存在联系.
- 在复发性与单次抑郁/焦虑发作之间发现了显著的积极关联.
结论:
- DEX-fPRS可能在HPA轴敏感性和情节复发中发挥作用,但不是整体诊断.
- 控制VEH-fPRS可能会捕获基线转录调节.
- 缺乏复制性需要谨慎解释和进一步验证发现.
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