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
Affiliations
Elizabeth K. Wood
Department of Psychiatry, Oregon Health & Science University, Portland, OR, USA
S. Andrew Aston
Department of Neuroscience, Brigham Young University, Provo, UT, USA
Patrick H. O’Connell
Department of Psychology, Brigham Young University, Provo, UT, USA
Elia Hafen
Department of Neuroscience, Brigham Young University, Provo, UT, USA
Andrea N. Skowbo
Department of Psychology, Brigham Young University, Provo, UT, USA
Melanie L. Schwandt
Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Poolesville, MD, USA
Stephen G. Lindell
Laboratory of Neurogenetics, Section of Comparative Behavioral Genomics, National Institute on Alcohol Abuse and Alcoholism, NIH, Rockville, MD, USA
Ellie Smith
Department of Psychology, Brigham Young University, Provo, UT, USA
Miranda Johnson
Department of Neuroscience, Brigham Young University, Provo, UT, USA
Zachary Baron
Department of Neuroscience, Brigham Young University, Provo, UT, USA
Natalia Gabrielle
Department of Psychology, Brigham Young University, Provo, UT, USA
Christina S. Barr
Laboratory of Neurogenetics, Section of Comparative Behavioral Genomics, National Institute on Alcohol Abuse and Alcoholism, NIH, Rockville, MD, USA
Stephen J. Suomi
Laboratory of Comparative Ethology, National Institute of Child Health and Human Development, Poolesville, MD, USA
David Goldman
Laboratory of Neurogenetics, Section of Comparative Behavioral Genomics, National Institute on Alcohol Abuse and Alcoholism, NIH, Rockville, MD, USA
J. Dee Higley
Department of Neuroscience, Brigham Young University, Provo, UT, USA
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.
