Genotypic variation in the promoter region of the CRH-248 gene interacts with early rearing experiences to disrupt the development of the HPA axis in infant rhesus macaques (Macaca mulatta).

IF 2.6 4区 心理学 Q2 BEHAVIORAL SCIENCES
Elizabeth K Wood, S Andrew Aston, Patrick H O'Connell, Elia Hafen, Andrea N Skowbo, Melanie L Schwandt, Stephen G Lindell, Ellie Smith, Miranda Johnson, Zachary Baron, Natalia Gabrielle, Christina S Barr, Stephen J Suomi, David Goldman, J Dee Higley
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引用次数: 0

Abstract

Aberrant functioning of the hypothalamic-pituitary-adrenal (HPA) axis is a hallmark of conditions such as depression, anxiety disorders, and post-traumatic stress disorder. Early-life adversity and genetic variation can interaction to disrupt HPA axis regulation, potentially contributing to certain forms of psychopathology. This study employs a rhesus macaque model to investigate how early parental neglect interacts with a single nucleotide polymorphism within the promoter region of the corticotropin-releasing hormone (CRH-248) gene, impacting the development of the HPA axis. For the initial six months of life, 307 rhesus monkey infants (n = 146 females, n = 161 males) were either reared with their mothers (MR) in conditions emulating the natural environment (control group) or raised without maternal care in groups with constant or 3-hours daily access to same-aged peers (NR). Blood samples collected on days 30, 60, 90, and 120 of life under stressful conditions were assayed for plasma cortisol and adrenocorticotropic hormone (ACTH) concentrations. Findings revealed that NR subjects exhibited a significant blunting of both ACTH and cortisol concentrations. Notably, there was a gene-by-environment interaction observed for ACTH and cortisol levels, with NR subjects with the polymorphism displaying higher ACTH concentrations and lower cortisol concentrations. To the extent that these results generalize to humans, they suggest that early parental neglect may render individuals vulnerable to HPA axis dysfunction, a susceptibility that is modulated by CRH-248 genotype-a gene-by-environment interaction that leaves a lasting developmental signature.

CRH-248基因启动子区域的基因型变异与早期饲养经历相互作用,干扰了猕猴幼年HPA轴的发育。
下丘脑-垂体-肾上腺(HPA)轴功能异常是抑郁症、焦虑症和创伤后应激障碍等疾病的标志。早期生活的逆境和遗传变异会相互作用,扰乱 HPA 轴的调节,从而可能导致某些形式的精神病理学。本研究采用猕猴模型来研究父母的早期忽视如何与促肾上腺皮质激素释放激素(CRH-248)基因启动子区域内的单核苷酸多态性相互作用,从而影响 HPA 轴的发育。在出生后的最初六个月,307只恒河猴婴儿(雌性146只,雄性161只)要么在模仿自然环境的条件下与母亲一起饲养(MR)(对照组),要么在没有母亲照料的情况下与同龄同伴一起饲养(NR),每天与同龄同伴接触3小时。在应激条件下,对受试者出生后第 30、60、90 和 120 天采集的血液样本进行血浆皮质醇和促肾上腺皮质激素(ACTH)浓度测定。研究结果表明,NR 受试者的促肾上腺皮质激素和皮质醇浓度均有显著降低。值得注意的是,在促肾上腺皮质激素和皮质醇水平方面观察到了基因与环境的相互作用,具有多态性的 NR 受试者表现出较高的促肾上腺皮质激素浓度和较低的皮质醇浓度。如果这些结果可以推广到人类,那么它们表明,早期父母的忽视可能会使个体易受HPA轴功能障碍的影响,而这种易感性会受到CRH-248基因型的调节--基因与环境的相互作用会留下持久的发育特征。
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来源期刊
CiteScore
5.60
自引率
0.00%
发文量
25
审稿时长
6-12 weeks
期刊介绍: The journal Stress aims to provide scientists involved in stress research with the possibility of reading a more integrated view of the field. Peer reviewed papers, invited reviews and short communications will deal with interdisciplinary aspects of stress in terms of: the mechanisms of stressful stimulation, including within and between individuals; the physiological and behavioural responses to stress, and their regulation, in both the short and long term; adaptive mechanisms, coping strategies and the pathological consequences of stress. Stress will publish the latest developments in physiology, neurobiology, molecular biology, genetics research, immunology, and behavioural studies as they impact on the understanding of stress and its adverse consequences and their amelioration. Specific approaches may include transgenic/knockout animals, developmental/programming studies, electrophysiology, histochemistry, neurochemistry, neuropharmacology, neuroanatomy, neuroimaging, endocrinology, autonomic physiology, immunology, chronic pain, ethological and other behavioural studies and clinical measures.
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