Retrospective studies in humans have identified characteristics that
promote stress resistance, including childhood exposure to moderately stressful
events (ie, stress inoculation).
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.
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.
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