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Karen J. Parker, PhD; Christine L. Buckmaster, BS; Alan F. Schatzberg, MD; David M. Lyons, PhD

Arch Gen Psychiatry. 2004;61:933-941.

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.

From the Department of Psychiatry and Behavioral Sciences, Stanford University Medical School, Stanford, Calif.

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