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Effects of sex and early maternal abuse on adrenocorticotropin hormone and cortisol responses to the corticotropin-releasing hormone challenge during the first 3 years of life in group-living rhesus monkeys

  • Mar M. Sanchez (a1), Kai Mccormack (a1) (a2), Alison P. Grand (a1), Richelle Fulks (a1), Anne Graff (a1) and Dario Maestripieri (a1) (a3)...

In this study we investigated the development of the hypothalamic–pituitary–adrenal (HPA) axis in 21 group-living rhesus monkeys infants that were physically abused by their mothers in the first few months of life and in 21 nonabused controls. Cortisol and adrenocorticotropin hormone (ACTH) responses to a corticotropin-releasing hormone (CRH) challenge were assessed at 6-month intervals during the subjects' first 3 years of life. Abused infants exhibited greater cortisol responses to CRH than controls across the 3 years. Abused infants also exhibited blunted ACTH secretion in response to CRH, especially at 6 months of age. Although there were no significant sex differences in abuse experienced early in life, females showed a greater cortisol response to CRH than males at all ages. There were no significant sex differences in the ACTH response to CRH, or significant interactions between sex and abuse in the ACTH or cortisol response. Our findings suggest that early parental maltreatment results in greater adrenocortical, and possibly also pituitary, responsiveness to challenges later in life. These long-term alterations in neuroendocrine function may be one the mechanisms through which infant abuse results in later psychopathologies. Our study also suggests that there are developmental sex differences in adrenal function that occur irrespective of early stressful experience. The results of this study can enhance our understanding of the long-term effects of child maltreatment as well as our knowledge of the development of the HPA axis in human and nonhuman primates.

Corresponding author
Address correspondence and reprint requests to: Dario Maestripieri, University of Chicago, 5730 South Woodlawn Avenue, Chicago, IL 60637; E-mail:
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Blank, M. S., Gordon, T. P., & Wilson, M. E. (1983). Effects of venipuncture on serum levels of prolactin, growth hormone, and cortisol in outdoor compound-housed female rhesus monkeys. Acta Endocrinologica, 102, 190195.
Born, J., Ditschumeit, X., Schreiber, M., Dodt, C., & Fehm, H. L. (1995). Effects of age and gender on pituitary–adrenocortical responsiveness in humans. European Journal of Endocrinology, 132, 705711.
Bowman, R. E., & Wolf, R. C. (1969). Plasma 17-hydroxycorticosteroid response to ACTH in M. mulatta: Dose, age, weight, and sex. Proceedings of the Society for Experimental Biology and Medicine, 130, 6164.
Boyce, W. T., Champoux, M., Suomi, S. J., & Gunnar, M. R. (1995). Salivary cortisol in nursery-reared rhesus monkeys: Reactivity to peer interactions and altered circadian activity. Developmental Psychobiology, 28, 257267.
Bugental, D. B., Martorell, G. A., & Barraza, V. (2003). The hormonal costs of subtle forms of infant maltreatment. Hormones & Behavior, 43, 237244.
Carrion, V., Weems, C., Ray, R., Glaser, B., Hessl, D., & Reiss, A. (2002). Diurnal salivary cortisol in pediatric posttraumatic stress disorder. Biological Psychiatry, 51, 575582.
Cicchetti, D., & Cohen, D. J. (Eds.). (2006). Developmental psychopathology. New York: Wiley.
Clarke, A. S. (1993). Social rearing effects on HPA activity over early development and in response to stress in rhesus monkeys. Developmental Psychobiology, 26, 433446.
De Bellis, M. D., Chrousos, G. P., Dorn, L. D., Burke, L., Helmers, K., Kling, M. A., et al. (1994). Hypothalamic–pituitary–adrenal axis dysregulation in sexually abused girls. Journal of Clinical Endocrinology & Metabolism, 78, 249255.
Glaser, D. (2000). Child abuse and neglect and the brain: A review. Journal of Child Psychology and Psychiatry, 41, 97116.
Gunnar, M. R., & Donzella, B. (2002). Social regulation of the cortisol levels in early human development. Psychoneuroendocrinology, 27, 199220.
Gunnar, M. R., & Fisher, P. A. (2006). The early experience, stress, and prevention network: Bringing basic research on early experience and stress neurobiology to bear on preventive interventions for neglected and maltreated children. Development and Psychopathology, 18, 651677.
Gunnar, M. R., & Quevedo, K. (2007). The neurobiology of stress and development. Annual Review of Psychology, 58, 145173.
Gunnar, M. R., & Vazquez, D. M. (2006). Stress neurobiology and developmental psychopathology. In: Cicchetti, D. & Cohen, D. (Eds.), Developmental psychopathology: Developmental neuroscience (pp. 533577. New York: Wiley.
Gust, D. A., Gordon, T. P., & Hambright, K. (1993). Response to removal from and return to a social group in adult male rhesus monkeys. Physiology and Behavior, 53, 599602.
Hart, J., Gunnar, M., & Cicchetti, D. (1995). Salivary cortisol in maltreated children: Evidence of relations between neuroendocrine activity and social competence. Development and Psychopathology, 7, 1126.
Hart, J., Gunnar, M., & Cicchetti, D. (1996). Altered neuroendocrine activity in maltreated children related to symptoms of depression. Development and Psychopathology, 8, 201214.
Heim, C., Newport, D. J., Bonsall, R., Miller, A. H., & Nemeroff, C. B. (2001). Altered pituitary–adrenal axis responses to provocative challenge tests in adult survivors of childhood abuse. American Journal of Psychiatry, 158, 575–180.
Heim, C., Newport, D. J., Heit, S., Graham, Y. P., Wilcox, M., Bonsall, R., Miller, A. H., & Nemeroff, C. B. (2000). Pituitary–adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood. Journal of the American Medical Association, 284, 292297.
Holsboer, F., Gerkin, A., Stalla, G., & Muller, A. (1987). Blunted aldosterone and ACTH release after human RH administration in depressed patients. American Journal of Psychiatry, 144, 229231.
Kaufman, J. (1991). Depressive disorders in maltreated children. Journal of the American Academy of Child & Adolescent Psychiatry, 30, 257265.
Kaufman, J., Birmaher, B., Perel, J., Dahl, R. E., Moreci, P., Nelson, B., Wells, W., & Ryan, N.D. (1997). The corticotropin-releasing hormone challenge in depressed abused, depressed nonabused, and normal control children. Biological Psychiatry, 42, 669679.
Kaufman, J., Brent, D., Birmaher, B., Perel, J., Dahl, R. E., Nelson, B., et al. (1993). Measures of family adversity, clinical symptomatology, and cortisol secretion in a sample of preadolescent depressed children. Paper presented at the Annual Meeting of the Society for Research in Child and Adolescent Psychopathology, Santa Fe, NM.
Maestripieri, D. (1993). Maternal anxiety in rhesus macaques (Macaca mulatta). I. Measurement of anxiety and identification of anxiety-eliciting situations. Ethology, 95, 1931.
Maestripieri, D. (1994). Infant abuse associated with psychosocial stress in a group-living pigtail macaque (Macaca nemestrina) mother. American Journal of Primatology, 32, 4149.
Maestripieri, D. (1995). Assessment of danger to themselves and their infants by rhesus macaque (Macaca mulatta) mothers. Journal of Comparative Psychology, 109, 416420.
Maestripieri, D. (1998). Parenting styles of abusive mothers in group-living rhesus macaques. Animal Behaviour, 55, 111.
Maestripieri, D. (2005). Early experience affects the intergenerational transmission of infant abuse in rhesus monkeys. Proceedings of the National Academy of Science of the United States of America, 102, 97269729.
Maestripieri, D., & Carroll, K. A. (1998). Risk factors for infant abuse and neglect in rhesus monkeys. Psychological Science, 9, 143145.
Maestripieri, D., Wallen, K., & Carroll, K. A. (1997). Infant abuse runs in families of group-living pigtail macaques. Child Abuse and Neglect, 21, 465471.
Maestripieri, D., Higley, J. D., Lindell, S. G., Newman, T. K., McCormack, K., & Sanchez, M. M. (2006). Early maternal rejection affects the development of monoaminergic systems and adult abusive parenting in rhesus macaques. Behavioral Neuroscience, 120, 10171024.
Maestripieri, D., Lindell, S. G., & Higley, J. D. (2007). Intergenerational transmission of maternal behavior in rhesus monkeys and its underlying mechanisms. Developmental Psychobiology, 49, 165171.
Maestripieri, D., McCormack, K., Lindell, S. G., Higley, J. D., & Sanchez, M. M. (2006). Influence of parenting style on the offspring's behavior and CSF monoamine metabolite levels in crossfostered and noncrossfostered female rhesus macaques. Behavioural and Brain Research, 175, 9095.
Maestripieri, D., Tomaszycki, M., & Carroll, K. A. (1999). Consistency and change in the behavior of rhesus macaque abusive mothers with successive infants. Developmental Psychobiology, 34, 2935.
McCormack, K. M., Sanchez, M. M., Bardi, M., & Maestripieri, D. (2006). Maternal care patterns and behavioral development of rhesus macaque abused infants in the first 6 months of life. Developmental Psychobiology, 48, 537550.
Meyer, J. S., & Bowman, R. E. (1972). Rearing experience, stress, and adrenocorticosteroids in the rhesus monkey. Physiology and Behavior, 8, 339343.
Nemeroff, C. B. (2004). Neurobiological consequences of childhood trauma. Journal of Clinical Psychiatry, 65, 1828.
Roelfsema, F., van den Berg, G., Frolich, M., Veldhus, J. D., van Eijk, A., Buurman, M. M., & Etman, B. H. B. (1993). Sex-dependent alteration in cortisol response to endogenous adrenocorticotropin. Journal of Clinical Endocrinology and Metabolism, 77, 234240.
Roy, A. (2002). Urinary free cortisol and childhood trauma in cocaine dependent adults. Journal of Psychiatry Research, 36, 173177.
Sanchez, M. M. (2006). The impact of early adverse care on HPA axis development: Nonhuman primate models. Hormones and Behavior, 50, 623631.
Sanchez, M. M., Noble, P. M., Lyon, C. K., Plotsky, P. M., Davis, M., Nemeroff, C. B., et al. (2005). Alterations in diurnal cortisol rhythm and acoustic startle response in non-human primates with adverse rearing. Biological Psychiatry, 57, 373381.
Scallet, A. C., Suomi, S. J., & Bowman, R. E. (1981). Sex differences in adrenocortical response to controlled agonistic encounters in rhesus monkeys. Physiology and Behavior, 26, 385390.
Scheer, F. A. J. L., & Buijs, R. M. (1999). Light affects morning salivary cortisol in humans. Journal of Clinical Endocrinology and Metabolism, 84, 33953398.
Tarullo, A. R., & Gunnar, M. R. (2006). Child maltreatment and the developing HPA axis. Hormones and Behavior, 50, 632639.
Teicher, M. H., Andersen, S. L., Polcari, A., Anderson, C. M., Navalta, C. P., & Kim, D. M. (2003). The neurobiological consequences of early stress and childhood maltreatment. Neuroscience and Biobehavioral Reviews, 27, 3344.
Troisi, A., & D'Amato, F. R. (1991). Anxiety in the pathogenesis of primate infant abuse: A pharmacological study. Psychopharmacology, 103, 571572.
Wilson, M. E., Gordon, T. P., & Collins, D. C. (1986). Ontogeny of luteinizing hormone secretion and first ovulation in seasonal breeding rhesus monkeys. Endocrinology, 118, 293301.
Yehuda, R., Halligan, S. L., & Grossman, R. (2001). Childhood trauma and risk for PTSD: Relationship to intergenerational effects of trauma, parental PTSD, and cortisol excretion. Development and Psychopathology, 13, 733753.
Zahn-Waxler, C., Shirtcliff, E. A., & Marceau, K. (2008). Disorders of childhood and adolescence: Gender and psychopathology. Annual Review of Clinical Psychology, 4, 275303.
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Development and Psychopathology
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