背景:围产期情绪和焦虑障碍(PMAD)包括一系列发生在怀孕期间和产后一年的心理健康障碍,影响了大约20%的女性。传统风险因素,如抑郁症和妊娠并发症如先兆子痫(PE)的病史是已知的。它们的预测效用,然而,没有足够的特异性或敏感性,无法为PMAD的临床决策或预防策略提供信息。早期识别和转诊治疗需要更好的诊断和预后模型。
目的:确定一组新的妊娠晚期血浆蛋白生物标志物是否可以确定谁在产后3个月内易患PMAD。
方法:我们研究了在两个时间点进行心理健康筛查的52名女性(N=34有PMAD风险,N=18名对照),在妊娠晚期和分娩后3个月再次。PMAD风险升高是通过筛选上述验证的抑郁症临界值来定义的(爱丁堡产后抑郁量表,EPDS≥12),焦虑(总体焦虑严重程度和损害量表,OASIS≥7)和/或PTSD(事件影响量表,IES>26)在两个时间点。使用基于适体的SomaLogicSomaScan®蛋白质组学测定技术筛选在妊娠晚期收集的血浆样品,以评估PMAD相关的1,305种蛋白质分析物表达的变化。进行独创性途径分析以强调在所有PMAD受试者和具有PMAD且没有先兆子痫的那些受试者(非PEPMAD受试者)中发现显著上调或下调的PMAD特异性蛋白之间的病理生理学关系。
结果:在主成分分析中,从53个重要的PMAD相关蛋白中,20个独特的蛋白特征将PMAD病例与对照区分开(P<0.05)。这些蛋白质包括分子,如NCAM1,NRCAM,NTRK3在神经元信号通路周围汇聚,调节轴突引导,星形胶质细胞分化和GABA能神经元的维持。有趣的是,当我们限制分析排除PE时,在主成分分析中,30蛋白特征将PMAD病例与所有对照区分开,没有重叠(P<0.001)。在非PEPMAD组中,我们观察到CXCL11,CXCL6,MIC-B等蛋白质的表达增加,β-2微球蛋白,调节白细胞迁移,炎症和免疫功能。
结论:PMAD参与者具有独特且独特的血浆蛋白特征,可调节多种神经元信号和促炎途径。需要更大样本量的其他验证研究来确定这些分子中的一些是否可以与传统的风险因素一起用于PMAD的早期检测。
Perinatal mood and anxiety disorders encompass a range of mental health disorders that occur during pregnancy and up to 1 year postpartum, affecting approximately 20% of women. Traditional risk factors, such as a history of depression and pregnancy complications including preeclampsia, are known. Their predictive utility, however, is not specific or sensitive enough to inform clinical decision-making or prevention strategies for perinatal mood and anxiety disorders. Better diagnostic and prognostic models are needed for early identification and referral to treatment.
This study aimed to determine if a panel of novel third-trimester plasma protein biomarkers in pregnant women can be used to identify those who have a high predisposed risk for perinatal mood and anxiety disorders within 3 months postpartum.
We studied 52 women (n=34 with a risk for perinatal mood and anxiety disorders and n=18 controls) among whom mental health screening was conducted at 2 time points, namely in the third trimester and again at 3 months postdelivery. An elevated perinatal mood and anxiety disorder risk was identified by screening individuals with above-validated cutoffs for depression (Edinburgh Postnatal Depression Scale ≥12), anxiety (Overall Anxiety Severity and Impairment Scale ≥7), and/or posttraumatic stress disorder (Impact of Events Scale >26) at both time points. Plasma samples collected in the third trimester were screened using the aptamer-based SomaLogic SomaScan proteomic assay technology to evaluate perinatal mood and anxiety disorder-associated changes in the expression of 1305 protein analytes. Ingenuity Pathway Analysis was conducted to highlight pathophysiological relationships between perinatal mood and anxiety disorder-specific proteins found to be significantly up- or down-regulated in all subjects with perinatal mood and anxiety disorder and in those with perinatal mood and anxiety disorders and no preeclampsia.
From a panel of 53 significant perinatal mood and anxiety disorder-associated proteins, a unique 20-protein signature differentiated perinatal mood and anxiety disorder cases from controls in a principal component analysis (P<.05). This protein signature included NCAM1,
NRCAM, and NTRK3 that converge around neuronal signaling pathways regulating axonal guidance, astrocyte differentiation, and maintenance of GABAergic neurons. Interestingly, when we restricted the analysis to subjects without preeclampsia, a 30-protein signature differentiated perinatal mood and anxiety disorder cases from all controls without overlap on the principal component analysis (P<.001). In the nonpreeclamptic perinatal mood and anxiety disorder group, we observed increased expression of proteins, such as CXCL11, CXCL6, MIC-B, and B2MG, which regulate leucocyte migration, inflammation, and immune function.
Participants with perinatal mood and anxiety disorders had a unique and distinct plasma protein signature that regulated a variety of neuronal signaling and proinflammatory pathways. Additional validation studies with larger sample sizes are needed to determine whether some of these molecules can be used in conjunction with traditional risk factors for the early detection of perinatal mood and anxiety disorders.