| Abstract | Background: Retrospective studies in humans have identified
characteristics that promote stress resistance, including
childhood exposure to moderately stressful events
(ie, stress inoculation).
Objective: Because of limited opportunities for prospective
studies in children, we tested whether exposure
to moderate stress early in life produces later stress
resistance in a primate model.
Design and Main Outcome Measures: Twenty
squirrel monkeys were randomized to intermittent
stress inoculation (IS; n=11) or a nonstress control
condition (NS; n=9) from postnatal weeks 17 to 27. At
postnatal week 35, each mother-offspring dyad underwent
testing in a moderately stressful novel environment
for inferential measures of offspring anxiety (ie,
maternal clinging, mother-offspring interactions, object
exploration, and food consumption) and stress hormone
concentrations (corticotropin [ACTH] and
cortisol). At postnatal week 50, after acclimation to an
initially stressful wire-mesh box attached to the home
cage, independent young monkeys underwent testing
for inferential measures of anxiety (ie, voluntary exploration
and play) in the box.
Results: In the novel environment test, IS compared with
NS offspring demonstrated diminished anxiety as measured
by decreased maternal clinging (P=.02), enhanced
exploratory behavior (P=.005), and increased food
consumption (P=.02). Mothers of IS offspring accommodated
offspring-initiated exploration (P=.009) and
served as a secure base more often compared with NS
mothers (P=.047). Compared with NS offspring, IS offspring
had lower basal plasma ACTH (P=.001) and cortisol
(P=.001) concentrations and lower corticotropin
(P=.04) and cortisol (P=.03) concentrations after stress.
In the subsequent home-cage wire-box test, IS offspring
demonstrated enhanced exploratory (P<.001) and play
(P=.008) behaviors compared with NS offspring.
Conclusions: These results provide the first prospective
evidence that moderately stressful early experiences
strengthen socioemotional and neuroendocrine resistance
to subsequent stressors. This preclinical model offers
essential opportunities to improve our understanding
and enhance prevention of human stress-related
psychiatric disorders by elucidating the etiology and neurobiology
of stress resistance. |
