Edvinsson Åsa, Bränn Emma, Hellgren Charlotte, Freyhult Eva, White Richard, Kamali-Moghaddam Masood, Olivier Jocelien, Bergquist Jonas, Boström Adrian E, Schiöth Helgi B, Skalkidou Alkistis, Cunningham Janet L, Sundström-Poromaa Inger
Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
Department of Medical Science, Bioinformatics Infrastructure for Life Sciences, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Psychoneuroendocrinology. 2017 Jun;80:15-25. doi: 10.1016/j.psyneuen.2017.02.027. Epub 2017 Feb 28.
Antenatal depression and use of serotonin reuptake inhibitors (SSRI) in pregnancy have both been associated with an increased risk of poor pregnancy outcomes, such as preterm birth and impaired fetal growth. While the underlying biological pathways for these complications are poorly understood, it has been hypothesized that inflammation may be a common physiological pathway. The aim of the present study was to assess peripheral inflammatory markers in healthy women, women with antenatal depression, and in women using SSRI during pregnancy.
160 healthy pregnant controls, 59 women with antenatal depression and 39 women on treatment with SSRIs were included. The relative levels of 92 inflammatory proteins were analyzed by proximity extension assay technology.
Overall, 23 of the inflammatory markers were significantly lower in women with antenatal depression and in women on treatment with SSRIs in comparison with the healthy controls. No difference in any of the inflammatory markers was observed between women with antenatal depression and those who were using SSRI. Top three inflammatory markers that were down-regulated in women with antenatal depression were TNF-related apoptosis-inducing ligand (TRAIL), p=0.000001, macrophage colony-stimulating factor 1 (CSF-1), p=0.000004, and fractalkine (CX3CL1), p=0.000005. Corresponding inflammatory markers in SSRI users were CSF-1, p=0.000011, vascular endothelial growth factor A (VEGF-A), p=0.000016, and IL-15 receptor subunit alpha (IL-15RA), p=0.000027. The inflammatory markers were negatively correlated with cortisone serum concentrations in controls, but not in the cases. Differential DNA methylation of was found for seven of these inflammatory markers in an independent epigenetics cohort.
Women with antenatal depression or on SSRI treatment have lower levels of a number of peripheral inflammatory markers than healthy pregnant controls. Hypothetically, this could be due to dysregulated switch to the pro-M2 milieu that characterizes normal third trimester pregnancy. However, longitudinal blood sampling is needed to elucidate whether the presumably dysregulated M2 shift is driving the development of antenatal depression or is a result of the depression.
产前抑郁以及孕期使用5-羟色胺再摄取抑制剂（SSRI）均与不良妊娠结局风险增加有关，如早产和胎儿生长受限。虽然对这些并发症的潜在生物学途径了解甚少，但据推测炎症可能是一条共同的生理途径。本研究的目的是评估健康女性、产前抑郁女性以及孕期使用SSRI的女性的外周炎症标志物。
纳入160名健康孕妇对照组、59名产前抑郁女性和39名接受SSRI治疗的女性。采用邻位延伸分析技术分析92种炎症蛋白的相对水平。
总体而言，与健康对照组相比，产前抑郁女性和接受SSRI治疗的女性中有23种炎症标志物显著降低。产前抑郁女性与使用SSRI的女性之间在任何炎症标志物上均未观察到差异。产前抑郁女性中下调的前三种炎症标志物是肿瘤坏死因子相关凋亡诱导配体（TRAIL），p = 0.000001，巨噬细胞集落刺激因子1（CSF-1），p = 0.000004，以及 fractalkine（CX3CL1），p = 0.000005。SSRI使用者中相应的炎症标志物是CSF-1，p = 0.000011，血管内皮生长因子A（VEGF-A），p = 0.000016，以及白细胞介素15受体亚基α（IL-15RA），p = 0.000027。在对照组中，炎症标志物与可的松血清浓度呈负相关，但在病例组中并非如此。在一个独立的表观遗传学队列中，发现其中7种炎症标志物存在DNA甲基化差异。
与健康孕妇对照组相比，产前抑郁或接受SSRI治疗的女性外周多种炎症标志物水平较低。据推测，这可能是由于向孕晚期正常妊娠特征性的促M2环境的转换失调所致。然而，需要进行纵向血液采样以阐明推测的M2转换失调是导致产前抑郁的原因还是抑郁的结果。
