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).
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.
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.