Rearing condition and rh5-HTTLPR interact to influence limbic-hypothalamic-pituitary-adrenal axis response to stress in infant macaques
Abstract
Background In humans and macaques, a promoter polymorphism that decreases transcription of the serotonin transporter gene is associated with anxiety. Serotonin transporter gene disruption in rodents produces anxious animals with exaggerated limbic-hypothalamic-pituitary-adrenal (LHPA) responses to stress. We wanted to determine whether serotonin transporter gene promoter variation (rh-5HTTLPR) and rearing condition would interact to influence endocrine responses to stress in infant rhesus macaques.Methods Animals were reared with their mothers (MR, n = 141) or in peer-only groups (PR, n = 67). At 6 months of age, adrenocorticotropic hormone (ACTH) and cortisol levels were determined at baseline and during separation stress. Serotonin transporter genotype (l/l and l/s) was determined with polymerase chain reaction followed by gel electrophoresis.Results Cortisol levels increased during separation, and there was a main effect of rearing condition, with decreased cortisol levels among PR macaques. Animals with l/s rh5-HTTLPR genotypes had higher ACTH levels than did l/l animals. Adrenocorticotropic hormone levels increased during separation, and there was a separation x rearing x rh5-HTTLPR interaction, such that PR-l/s animals had higher ACTH levels during separation than did other animals studied.Conclusions These data demonstrate that serotonin transporter gene variation affects LHPA axis activity and that the influence of rh5-HTTLPR on hormonal responses during stress is modulated by early experience.
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The 5-HTTLPR genotype influenced the hormonal responses of the macaque monkeys during stress, while this influence was moderated by early experience.
“For example, the 5-HTTLPR genotype influenced the hormonal responses of the macaque monkeys during stress, while this influence was moderated by early experience 29.”
From Resilience in mental health: linking psychological and neurobiological perspectives. (2013) · cites this paper as [29]
Non-human primates with gene variants associated with depression risk in abused children show larger cortisol responses to psychosocial stressors.
“In non-human primates, individuals carrying gene variants associated with risk for depression in abused children (e.g., Caspi et al., 2003), exhibit larger cortisol responses to psychosocial stressors”
From The Differential Impacts of Early Physical and Sexual Abuse and Internalizing Problems on Daytime Cortisol Rhythm in School-Aged Children (2010) · cites this paper as Barr et al., 2004
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References 56 · Cited by 385
- Authors
- Barr, C. S., Newman, T. K., Shannon, C., Parker, C., Dvoskin, R. L., Becker, M. L., Schwandt, M., Champoux, M., Lesch, K. P., Goldman, D., Suomi, S. J., & Higley, J. D.
- Affiliations
- National Institutes of Health (US)
- University of Würzburg (DE)
- Corresponding author
- Barr, Christina S
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2004-04
- Volume
- 55
- Issue
- 7
- Pages
- 733-738
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2066397039
- Cited by
- 385
- References
- 56
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 2 · 2022: 5 · 2021: 4 · 2020: 4 · 2019: 28 · 2018: 9 · 2017: 11 · 2016: 11 · 2015: 17 · 2014: 24 · 2013: 22 · 2012: 26
- FWCI
- 10.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- serotonin transporter gene, 5-HTTLPR, rhesus monkeys, maternal care, peer rearing, separation stress, cortisol, ACTH, hypothalamic-pituitary-adrenal axis, gene-environment interaction, anxiety, early life experience, infant development
- MeSH terms
- Animals, Animals, Newborn, Arousal, Carrier Proteins, Chromosome Deletion, DNA Transposable Elements, Female, Hydrocortisone, Hypothalamo-Hypophyseal System, Limbic System, Macaca mulatta, Male, Maternal Deprivation, Membrane Glycoproteins, Nerve Tissue Proteins, Peer Group, Pituitary-Adrenal System, Promoter Regions, Genetic, Serotonin, Social Environment, Stress, Psychological, Genetic Variation, Base Pairing, Membrane Transport Proteins, Serotonin Plasma Membrane Transport Proteins
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