Department of Psychiatry and Mental Health, University of Cape Town, South Africa; Neuroscience Institute, University of Cape Town, South Africa.
Stress, Psychiatry and Immunology Laboratory, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, UK.
Brain Behav Immun. 2022 Oct;105:160-168. doi: 10.1016/j.bbi.2022.07.001. Epub 2022 Jul 6.
Antenatal exposure to maternal psychological adversity, including depression, increases the risk of impaired neurodevelopment in children. The underlying biological mechanisms remain unclear, especially in early life during critical windows of development and maturation. This study investigated the association of antenatal maternal depression, maternal and early life inflammatory markers and neurodevelopmental outcomes in children at 2 years of age.
A subgroup of mothers and their children (n = 255) that were enrolled in a South African birth cohort study, the Drakenstein Child Health Study, were followed from the antenatal period through to 2 years of child age. Maternal depressive symptoms were measured by the Beck Depression Inventory (BDI-II) at 26 weeks gestation. Serum inflammatory markers [granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ (IFN-γ), interleukin IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, tumour necrosis factor-α (TNF-α), neutrophil gelatinase-associated lipocalin (NGAL) and metalloproteinase-9 (MMP-9)] were measured in mothers at enrolment and in their children at 6-10 weeks and at 2 years. Neurodevelopment was assessed at 2 years using the Bayley Scales of Infant and Toddler Development III.
Antenatal depressive symptoms (present in 25% of the mothers) were significantly associated with higher levels of IL-7 (p = 0.008), IL-8 (p = 0.019) and TNF-α (p = 0.031) in the mothers after correcting for sociodemographic and lifestyle factors. Serum IL-1β and NGAL levels were significantly elevated over time in children born to mothers with depressive symptoms compared to those without depression, after controlling for maternal and child health and sociodemographic factors. Elevated infant IL-1β at 6-10 weeks of age partially mediated the association of maternal depressive symptoms with poorer language scores at 2 years.
Alterations in early life immunity, as reflected by elevated IL-1β, is a potential pathway through which antenatal maternal depressive symptoms may impact language development in young children.
产前暴露于母体心理逆境,包括抑郁,会增加儿童神经发育受损的风险。其潜在的生物学机制尚不清楚,尤其是在儿童发育和成熟的关键窗口期的早期生命阶段。本研究调查了产前母亲抑郁、母亲和早期生活炎症标志物与 2 岁儿童神经发育结局之间的关系。
本研究纳入了南非出生队列研究——德肯斯坦儿童健康研究的一部分母亲及其子女(n=255),从产前阶段一直随访至儿童 2 岁。在 26 周妊娠时使用贝克抑郁量表(BDI-II)评估母亲的抑郁症状。在母亲入组时和儿童 6-10 周及 2 岁时检测血清炎症标志物[粒细胞-巨噬细胞集落刺激因子(GM-CSF)、干扰素-γ(IFN-γ)、白细胞介素-1β(IL-1β)、IL-2、IL-4、IL-5、IL-6、IL-7、IL-8、IL-10、IL-12p70、IL-13、肿瘤坏死因子-α(TNF-α)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)和基质金属蛋白酶-9(MMP-9)]。在 2 岁时使用贝利婴幼儿发育量表 III 评估神经发育。
产前抑郁症状(存在于 25%的母亲中)与母亲产后 IL-7(p=0.008)、IL-8(p=0.019)和 TNF-α(p=0.031)水平升高显著相关,且这些结果在调整了社会人口统计学和生活方式因素后仍然存在。与无抑郁的母亲所生的儿童相比,患有抑郁的母亲所生的儿童的血清 IL-1β 和 NGAL 水平随着时间的推移呈显著升高趋势,且这些结果在调整了母婴健康和社会人口统计学因素后仍然存在。6-10 周龄时婴儿 IL-1β 水平升高部分介导了母亲抑郁症状与 2 岁时语言评分较差之间的关联。
早期生命免疫的改变,如 IL-1β 升高,可能是产前母亲抑郁影响幼儿语言发育的潜在途径。