McCormack Kai, Bramlett Sara, Morin Elyse L, Siebert Erin R, Guzman Dora, Howell Brittany, Sanchez Mar M
Department of Psychology, Spelman College, 350 Spelman Lane, Atlanta, GA 30314, USA.
Emory National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
Biology (Basel). 2025 Feb 15;14(2):204. doi: 10.3390/biology14020204.
Early life adversity (ELA) is a known risk factor for psychopathology, including stress-related anxiety and depressive disorders. The underlying mechanisms and developmental changes remain poorly understood. A likely underpinning is the impact of ELA on the development of stress response systems, including the hypothalamic-pituitary-adrenal (HPA) axis. Our group studied a translational ELA model of spontaneous infant maltreatment by the mother in rhesus macaques, where we used a cross-fostering design to randomly assign infant macaques to either Control or Maltreating (MALT) foster mothers at birth to examine the impact of adverse caregiving on the development of the HPA axis, while controlling for the confounding effects of heritable and prenatal factors. We previously reported higher levels of plasma and hair cortisol (CORT) across the first 6 postnatal months (equivalent to the first 2 years of life in humans) in the MALT than in the Control infants. Here, we followed the same cohort of infants longitudinally to assess the long-term developmental impact of this adverse experience on HPA axis function during the juvenile (12, 18 months) and late adolescent (~5 years) periods. For this, we collected measurements of diurnal CORT rhythm and glucocorticoid negative feedback using the dexamethasone suppression test (DST). At 12 months, we found higher diurnal CORT secretion in MALT females compared to Control females, and impaired negative feedback in response to the DST in both sexes in the MALT group. However, ELA group differences in the HPA axis function disappeared by 18 months and late adolescence, while sex differences in diurnal CORT rhythm emerged or became stronger. These results suggest that infant maltreatment causes dysregulation of the HPA axis during the first year of life, with HPA axis function normalizing later, during the pre-pubertal juvenile period and adolescence. This suggests that the impact of maltreatment on HPA axis function may be transient, at least if the adverse experience stops. Our findings are consistent with human evidence of recalibration/normalization of HPA axis function during adolescence in children that switch from adverse/deprived environments to supportive adoptive families. This research has broad implications regarding the biological processes that translate ELA to psychopathology during development and the pathways to resiliency.
早年生活逆境（ELA）是精神病理学的一个已知风险因素，包括与压力相关的焦虑和抑郁障碍。其潜在机制和发育变化仍知之甚少。一个可能的基础是ELA对压力反应系统发育的影响，包括下丘脑-垂体-肾上腺（HPA）轴。我们的研究小组研究了恒河猴母亲对婴儿的自发性虐待的转化性ELA模型，我们采用交叉寄养设计，在出生时将幼猴随机分配给对照或虐待（MALT）寄养母亲，以研究不良养育对HPA轴发育的影响，同时控制遗传和产前因素的混杂效应。我们之前报告说，在出生后的前6个月（相当于人类生命的前2年），MALT组的血浆和毛发皮质醇（CORT）水平高于对照组婴儿。在这里，我们对同一组婴儿进行纵向跟踪，以评估这种不良经历对青少年期（12、18个月）和青少年晚期（约5岁）HPA轴功能的长期发育影响。为此，我们使用地塞米松抑制试验（DST）收集了昼夜CORT节律和糖皮质激素负反馈的测量数据。在12个月时，我们发现MALT组雌性的昼夜CORT分泌高于对照组雌性，并且MALT组两性对DST的负反馈受损。然而，到18个月和青少年晚期，ELA组在HPA轴功能上的差异消失了，而昼夜CORT节律的性别差异出现或变得更强。这些结果表明，婴儿期虐待会导致生命第一年HPA轴失调，而在青春期前的青少年期和青春期后期，HPA轴功能会恢复正常。这表明虐待对HPA轴功能的影响可能是短暂的，至少如果不良经历停止的话。我们的研究结果与人类证据一致，即从不良/贫困环境转向支持性收养家庭的儿童在青春期HPA轴功能会重新校准/正常化。这项研究对于在发育过程中将ELA转化为精神病理学的生物学过程以及恢复力的途径具有广泛的意义。
