不同的神经发育特征的性别特异性转录基因组为抑郁症的多基因风险评分基于性别特异性转录基因组
Sarah S Rashid1,2, Kevan P Clifford1,3, Amy E Miles1
1Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health.
medRxiv : the preprint server for health sciences
|August 6, 2025
概括
基于性别特异的转录基因组的多基因风险评分 (tPRS) 揭示了青少年男性和女性主要抑郁症 (MDD) 风险的独特神经发育途径,不同影响大脑结构和抑郁症状.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 是一个遗传学.
- 精神病学是一个精神病学.
背景情况:
- 大型抑郁症 (MDD) 呈现出性别特异的流行率和转录基因特征.
- 之前的工作开发了一个基于转录基因组的通用多基因风险评分 (tPRS),具有特定性别的大脑和症状关联.
- 了解性别特异性MDD遗传风险对神经发育的早期影响至关重要.
研究的目的:
- 开发和评估性别特异性tPRS (tPRS-F,tPRS-M) 对青少年大脑结构和抑郁症状的影响.
- 调查导致MDD易受伤害的特定性别神经发育途径.
主要方法:
- 使用性别特异性MDD基因表达数据开发出女性特异性 (tPRS-F) 和男性特异性 (tPRS-M) 评分.
- 在5002名青少年 (年龄为8.9-11.0岁) 中,在基线和2年随访时评估皮质厚度,表面积,皮质下体积和抑郁症状的相关性.
- 研究了皮下体积对tPRS-F和抑郁症状之间的关系的调解效应.
主要成果:
- 男性特异性tPRS (tPRS-M) 与男性的抑郁症状增加和左后带带皮层变厚有关.
- 女性特异性tPRS (tPRS-F) 与女性右,右尾状和双边海马体体积的减少有关.
- 皮下体积部分介导了tPRS-F对女性抑郁症状的影响. 没有观察到跨性别效应.
结论:
- 性别特定的与抑郁症相关的基因表达转变有助于MDD的独特神经发育脆弱性表型.
- 这些发现凸显了早期MDD风险背后的性别特异性生物机制.
- tPRS-F和tPRS-M提供了潜在的工具,用于识别性别特异性发展轨迹的MDD.
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