King's College London, Institute of Psychiatry, Psychology and Neuroscience, Department of Psychological Medicine, London SE5 9RT, UK.
King's College London, Institute of Psychiatry, Psychology and Neuroscience, Department of Psychological Medicine, London SE5 9RT, UK; King's College London, Institute of Psychiatry, Psychology and Neuroscience, Department of Basic and Clinical Neuroscience, The Maurice Wohl Clinical Neuroscience Institute, Cutcombe Road, London SE5 9RX, UK.
Brain Behav Immun. 2022 Jan;99:223-230. doi: 10.1016/j.bbi.2021.09.020. Epub 2021 Oct 10.
Stress in pregnancy is associated with adverse outcomes in offspring, and developmental programming is a potential mechanism. We have previously shown that depression in pregnancy is a valid and clearly defined stress paradigm, and both maternal antenatal and offspring stress-related biology is affected. This study aims to clarify whether maternal biology in pregnancy and offspring outcomes can also be influenced by a history of a prior depression, in the absence of depression in pregnancy. Our primary hypothesis is that, similarly to women with depression in pregnancy, women with a history of depression but who are not depressed in pregnancy will have increased cortisol secretion and markers of immune system function, and that their offspring will have poorer neuro-developmental competencies and increased cortisol stress response.
A prospective longitudinal design was used in 59 healthy controls and 25 women with a past history of depression who were not depressed in pregnancy, named as 'history-only', and their offspring. Maternal antenatal stress-related biology (cortisol and markers of immune system function) and offspring outcomes (gestational age at birth, neonatal neurobehaviour (Neonatal Behavioural Assessment Scale, NBAS), cortisol stress response and basal cortisol at 2 and 12 months) and cognitive, language and motor development (Bayley Scales of Infant and Toddler Development (BSID)) were measured.
Compared with healthy pregnant women, those with a history of depression who remain free of depression in pregnancy exhibit increased markers of immune system function in pregnancy: IL-8 (d = 0.63, p = 0.030), VEGF (d = 0.40, p = 0.008) and MCP-1 (d = 0.61, p = 0.002) and have neonates with lower neurobehavioural scores in most areas, reaching statistical significance in thesocial-interactive (d = 1.26, p = 0.015) cluster. However, there were no differences in maternal or offspring HPA axis function or in infant development at 12 months.
Our study indicates that pregnant women with a history of depression have increased markers of immune system function, and their offspring show behavioural alterations that may be the effects of in utero programming, epigenetic factors or genetic predisposition.
孕期压力与后代不良结局有关，而发育编程是一种潜在的机制。我们之前已经表明，孕期抑郁是一种有效的、明确界定的压力范例，且母体产前和后代应激相关生物学均受到影响。本研究旨在阐明，即使在孕期没有抑郁的情况下，既往抑郁史是否也会影响母体生物学和后代结局。我们的主要假设是，与孕期抑郁的女性类似，既往抑郁但孕期无抑郁的女性会出现皮质醇分泌增加和免疫系统功能标志物改变，且其后代的神经发育能力较差，皮质醇应激反应增加。
本研究采用前瞻性纵向设计，纳入了 59 名健康对照者和 25 名既往抑郁但孕期无抑郁的女性（称为“仅既往抑郁”）及其后代。测量了母体产前应激相关生物学（皮质醇和免疫系统功能标志物）和后代结局（出生时的胎龄、新生儿神经行为（新生儿行为评估量表，NBAS）、皮质醇应激反应和 2 个月及 12 个月时的基础皮质醇）以及认知、语言和运动发育（贝利婴幼儿发育量表（BSID））。
与健康孕妇相比，那些既往抑郁但孕期无抑郁的女性在孕期表现出更高的免疫系统功能标志物：白细胞介素 8（d=0.63，p=0.030）、血管内皮生长因子（d=0.40，p=0.008）和单核细胞趋化蛋白 1（d=0.61，p=0.002），且新生儿在大多数领域的神经行为评分较低，在社会互动方面达到统计学显著水平（d=1.26，p=0.015）。然而，母婴 HPA 轴功能或婴儿 12 个月时的发育并无差异。
我们的研究表明，既往抑郁的孕妇有更高的免疫系统功能标志物，且其后代表现出行为改变，这些改变可能是宫内编程、表观遗传因素或遗传易感性的影响。
