Alterations in diurnal cortisol rhythm and acoustic startle response in nonhuman primates with adverse rearing

Biol Psychiatry. 2005 Feb 15;57(4):373-81. doi: 10.1016/j.biopsych.2004.11.032.


Background: Early adverse experiences represent risk factors for the development of anxiety and mood disorders. Studies in nonhuman primates have largely focused on the impact of protracted maternal and social deprivation, but such intense manipulations also result in severe social and emotional deficits very difficult to remediate. This study attempts to model more subtle developmental perturbations that may increase the vulnerability for anxiety/mood disorders but lack the severe deficits associated with motherless rearing.

Methods: We investigated the consequences of repeated maternal separations between 3 to 6 months of age on rhesus monkeys' hypothalamic-pituitary-adrenal (HPA) axis function and acoustic startle reactivity.

Results: Repetitive maternal separation led to increased cortisol reactivity to the separation protocol in female infants and alterations in mother-infant interaction. It also resulted in a flattened diurnal rhythm of cortisol secretion and increased acoustic startle reactivity at later ages.

Conclusions: Macaques with adverse rearing exhibited short-term and long-term alterations in HPA axis function and increased acoustic startle response comparable with changes associated with mood/anxiety disorders. The magnitude of HPA axis reactivity to the separations and the alterations in mother-infant relationship detected during the separation protocol predicted some of the alterations in HPA axis and emotionality exhibited later in life.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acoustic Stimulation / methods
  • Age Factors
  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Behavior, Animal
  • Circadian Rhythm / physiology*
  • Dose-Response Relationship, Radiation
  • Female
  • Hydrocortisone / blood*
  • Hypothalamo-Hypophyseal System / physiology
  • Macaca mulatta
  • Male
  • Maternal Deprivation*
  • Pituitary-Adrenal System / physiology
  • Reflex, Acoustic / physiology*
  • Sex Factors
  • Video Recording / methods


  • Hydrocortisone