早期生活逆境/压力(ELA/ELS),特别是不良的护理经历,如儿童虐待(MALT),是精神病理学的主要危险因素,包括焦虑症等精神疾病,抑郁症,多动症,和药物滥用。然而,这些变化在发展过程中如何展开,以及潜在的机制仍然知之甚少,因为很难前瞻性和纵向研究人类的早期发育阶段,几乎不可能将产后护理效果与遗传性状分开。这项研究检查了“养育”(产妇护理)与“自然”(可遗传,生物母体因素)对非人灵长类动物婴儿的社会情感,应激神经内分泌,和身体发育。为此,我们使用了母亲对婴儿进行虐待的翻译和自然主义猕猴模型,并在出生时随机分配给有虐待婴儿史的母亲(MALT组,n=22)或对有能力的母亲(对照组,n=20)。在生命的前6个月(大约相当于人类的2年),我们研究了母婴关系的发展,以及婴儿的社会行为和情绪反应。并行,我们纵向评估了下丘脑-垂体-肾上腺(HPA)轴功能,使用头发皮质醇积累的测量,和基础的早晨血浆皮质醇。我们确定了MALT寄养母亲在产妇护理中表现出的广泛损害,超越虐待(身体虐待,拒绝)事件,这表明与对照组相比,MALT寄养母亲为婴儿提供的护理质量总体较低。MALT婴儿在开始时表现出改变,并且与母亲的接近度中断,与对照组相比,情绪反应性也提高了。最引人注目的是HPA轴心的发现,与对照组相比,MALT婴儿在出生后的前6个月中显示出更高的血浆皮质醇水平,以及从出生到第6个月的头发皮质醇积累(慢性压力的标志)。没有检测到对身体生长的护理影响,排除了母体营养的混杂效应,新陈代谢,等。一起来看,这些结果表明,MALT和对照婴儿的发育轨迹是不同的,以情绪反应水平提高为标志,MALT动物中HPA活性增加和母婴相互作用的改变。这些发现似乎是由于产后产妇护理的特定影响,而不是遗传自母亲的生物/行为特征,或者由于产前压力引起的产前编程,因为交叉培养设计控制了这些潜在因素。然而,我们还发现了一些有趣的生物学效应,表明某些表型可遗传传播。在出生后的前6个月中,延长的HPA轴激活预计会对大脑产生长期影响,生理,和MALT后代的行为发育。
Early life adversity/stress (ELA/ELS), particularly adverse caregiving experiences such as child maltreatment (MALT), is a main risk factor for psychopathology, including psychiatric disorders such as anxiety, depression, ADHD, and substance abuse. Yet how these alterations unfold during development and the underlying mechanisms remain poorly understood, as it is difficult to prospectively and longitudinally
study early developmental phases in humans, and nearly impossible to disentangle postnatal caregiving effects from heritable traits. This
study examined the specific effects of \"nurture\" (maternal care) versus \"nature\" (heritable, biological maternal factors) on nonhuman primate infant socioemotional, stress neuroendocrine, and physical development. For this we used a translational and naturalistic macaque model of infant maltreatment by the mother with randomized assignment at birth to either mothers with a history of maltreating their infants (MALT group, n = 22) or to competent mothers (Control group, n = 20). Over the first 6 months of life (roughly equivalent to 2 years in humans), we examined the development of the mother-infant relationship, as well as infants\' social behavior and emotional reactivity. In parallel, we assessed hypothalamic-pituitary-adrenal (HPA) axis function longitudinally, using measures of hair cortisol accumulation, and basal morning plasma cortisol. We identified broad impairments in maternal care exhibited by MALT foster mothers, beyond maltreatment (physical abuse, rejection) events, suggesting that MALT foster mothers provide an overall lower quality of care to their infants compared to Controls. MALT infants exhibited alterations in their initiations and breaks of proximity towards their mothers, as well as heightened emotional reactivity in comparison to Controls. Most striking are the HPA axis findings, with MALT infants showing higher levels of plasma cortisol across the first 6 postnatal months as well as higher hair cortisol accumulation from birth through month 6 (a signature of chronic stress) than Controls. No caregiving effects were detected on physical growth, which ruled out confounding effects of maternal nutrition, metabolism, etc. Taken together, these results suggest that the developmental trajectory of MALT and Control infants is different, marked by heightened levels of emotional reactivity, increased HPA activity and alterations in mother-infant interactions in MALT animals. These findings appear to be due to specific effects of postnatal maternal care, and not to biological/ behavioral traits inherited from the mother, or due to prenatal programming caused by prenatal stress, as the cross-fostering design controlled for these potential factors. However, we also detected a couple of interesting biological effects suggesting heritable transmission of some phenotypes. The prolonged HPA axis activation during the first 6 postnatal months of life is expected to have long-term consequences for brain, physiological, and behavioral development in MALT offspring.