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Long-term effects of prenatal synthetic glucocorticoid exposure on psychosocial stress reactivity and volitional control in children and adolescents

产前合成糖皮质激素暴露对儿童和青少年社会心理应激反应和意志控制的长期影响

基本信息

批准号：
265642394
负责人：
Professorin Dr. Nina Alexander, Ph.D.
金额：
--
依托单位：
Professur für Biopsychologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2014
资助国家：
德国
起止时间：
2013-12-31 至 2018-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/265642394?language=en
关键词：
Long term effects prenatal synthetic

项目摘要

Interactions between the developing individual and his or her developmental contexts are crucial for experience-dependent tuning of behavioural and brain development. Prenatal exposures to unfavorable events in the gestational environment, such as maternal stress or depression, glucocorticoids and substance abuse, are among the earliest adverse contextual influences on development. Of particular relevance to this project are long-term effects of prenatal synthetic glucocorticoid (sGC) exposure on the development of social stress reactivity and volitional control. Thus far, research on hypothalamus-pituitary-adrenal (HPA) axis functioning in humans exposed to antenatal sGC treatment is currently limited to the assessment of a single cortisol baseline measure and stress-induced cortisol secretion shortly after birth with preterm birth being an important confounder. Furthermore, although the HPA-axis is tightly linked to brain networks, such as the prefrontal circuitry, that subserve cognitive and motivational regulatory functions, long-term effects of antenatal sGC exposure on these regulatory functions in humans have been sparsely addessed and are mostly limited to behavioral assessments. To go beyond the current state of the art, this proposed project will assess long-term effects of antenatal sGC on psychosocial stress reactivity, behavioral and brain evoked potential measures of volitional control, using a retrospective longitudinal design. The proposed project has three aims: First, we plan to carry out a comprehensive assessment of hypothalamus-pituitary-adrenal (HPA) axis functioning in childhood and adolescence to explore (a) whether our previously observed effects of prenatal sGC exposure on stress reactivity in children would persist into adolescence and (b) whether these effects would generalize to measures of long-term changes in basal cortisol secretion. Second, by measuring electroencephalography (EEG) we aim to investigate the effects of antenatal sGC exposure on evoked brain potentials associated with cognitive monitoring, which are known to involve monoaminergic modulations and brain circuits that are tightly linked to the HPA-axis functions. A third goal of the current project is to investigate epigenetic modifications as a potential mechanism in mediating long-term effects of antenatal sGC on stress-related and cognitive measures. Other than the potential gain of understanding basic mechanisms that relate antenatal sGC exposure, monoaminergic modulation and cognition during child and adolescent development, a deeper understanding of long-term effects of antenatal sGC exposure is also of important clinical relevance given the widespread use of sGC (7 to 10% of women in Europe and North America) in obstetric care.

发展中的个人和他或她的发展环境之间的相互作用是至关重要的经验依赖的行为和大脑发育的调整。产前暴露于妊娠环境中的不利事件，如母亲的压力或抑郁症，糖皮质激素和药物滥用，是对发育的最早的不利背景影响之一。与该项目特别相关的是产前合成糖皮质激素（sGC）暴露对社会压力反应性和意志控制发展的长期影响。到目前为止，对暴露于产前sGC治疗的人类中下丘脑-垂体-肾上腺（HPA）轴功能的研究目前仅限于评估单个皮质醇基线测量和出生后不久的应激诱导的皮质醇分泌，早产是一个重要的混杂因素。此外，虽然HPA轴与大脑网络（如前额叶回路）紧密相关，有助于认知和动机调节功能，但产前sGC暴露对人类这些调节功能的长期影响很少，并且主要限于行为评估。为了超越目前的最新技术水平，该拟议项目将使用回顾性纵向设计评估产前sGC对心理社会应激反应、行为和脑诱发电位意志控制措施的长期影响。该项目有三个目标：首先，我们计划对儿童和青少年的下丘脑-垂体-肾上腺（HPA）轴功能进行全面评估，以探索（a）我们先前观察到的产前sGC暴露对儿童应激反应的影响是否会持续到青春期，以及（B）这些影响是否会推广到基础皮质醇分泌的长期变化的测量。其次，通过测量脑电图（EEG），我们的目标是研究产前sGC暴露对与认知监测相关的诱发脑电位的影响，已知认知监测涉及与HPA轴功能紧密相关的单胺能调制和脑回路。本项目的第三个目标是研究表观遗传修饰作为调解产前sGC对压力相关和认知措施的长期影响的潜在机制。除了了解与产前sGC暴露、儿童和青少年发育期间单胺能调节和认知相关的基本机制的潜在增益外，鉴于sGC（欧洲和北美7%至10%的女性）在产科护理中的广泛使用，更深入地了解产前sGC暴露的长期影响也具有重要的临床意义。