Early Environmental Regulation of Glucocorticoid Feedback Sensitivity in Young Adult Monkeys

Abstract

Variations in maternal care induce in neonatal rodents life-long changes in glucocorticoid feedback regulation of the hypothalamic-pituitary-adrenal axis. This aspect of plasticity in neuroendocrine development has not been established in primates. We assessed, in young adult squirrel monkeys, postnatal rearing effects on cortisol-induced suppression of corticotropin-releasing factor (CRF) stimulated secretion of adrenocorticotropic hormone (ACTH). Offspring of randomly bred monkeys were periodically removed from natal groups between 13 and 21 weeks of age. In two other postnatal rearing conditions, systematic differences in maternal availability were produced by manipulating the effort required of lactating mothers to successfully find food. All offspring were subsequently administered, 3-5 years later on two occasions, an intravenous ovine CRF injection preceded 60 min earlier by placebo or cortisol pretreatment. The difference between CRF-stimulated time-integrated secretion of ACTH following placebo vs cortisol pretreatment served as an index of glucocorticoid negative feedback. Difference scores were greatest in monkeys previously separated from natal groups. This finding was not attributable to significant rearing condition differences in plasma cortisol levels achieved following pretreatment with exogenous cortisol, nor plasma ACTH levels produced when the CRF injection was preceded by pretreatment with placebo. The results suggest that postnatal experiences altered glucocorticoid feedback in monkeys at least through early adulthood. This conclusion supports retrospective reports indicating that, for humans with major mood and anxiety disorders, systematic differences in glucocorticoid feedback may reflect neural mechanisms in development linking early life stress with psychopathology in adulthood.

Importance of Studying the Contributions of Early Adverse Experience to Neurobiological Findings in Depression

“…If increased cortisol concentrations were observed, these were positively correlated with alcohol preference (Fahlke et al, 2000). Squirrel monkeys exposed to repeated social separations also demonstrate reduced cortisol responses to later separation stress and increased glucocorticoid feedback sensitivity (Lyons et al, 1999(Lyons et al, , 2000. Similarly, decreased morning cortisol excretion was recently reported for marmoset monkeys exposed to repeated maternal separation .…”

Maternal, not paternal, PTSD is related to increased risk for PTSD in offspring of Holocaust survivors

“…The animal literature which focuses on the biological outcomes in the adult offspring of early maternal behaviors (e.g., Lyons et al, 2000;Ladd et al, 2005;Champagne & Meaney, 2001;Schmidt et al, 2002); does not preclude a role for paternal behavior in the modulation of subsequent offspring behavior or risk for psychopathology. Animal studies do not tend to examine effects of paternal behavior.…”

The Psychobiology of Neglect

“…Primates subjected to prolonged periods of maternal and social deprivation have altered catecholamine (Martin, Sackett, Gunderson, & Goodlin-Jones, 1988) and cortisol (Lyons, Yang, Mobley, Nickerson, & Schatzberg, 2000) function and impaired immune function (Lubach, Coe, & Erhler, 1995). Similarly, maltreated children with or without a diagnosis of PTSD show alterations of the development of catecholamine containing biological stress response systems (for review, see .…”