Edited by Ian H. Gotlib, Stanford University, Stanford, CA, and accepted by Editorial Board Member Renée Baillargeon October 8, 2019 (received for review June 10, 2019)
This longitudinal study demonstrates within-individual pubertal recalibration of the HPA axis in humans. Findings provide empirical support for an adolescent window of plasticity during which the brain resamples the environment and alters HPA functioning if the current caregiving environment is sufficiently different from the early caregiving environment in which the system was originally organized. This suggests that intervention efforts to improve outcomes for children who have experienced early life adversity should include a focus on the prepubertal and peripubertal period in order to maximize their impact on recalibrating systems like the HPA axis.
Nonhuman animal models reveal that the hypothalamic–pituitary–adrenocortical (HPA) axis calibrates to the harshness of the environment during a sensitive period in infancy. Humans exposed to depriving institutional care in infancy show reduced HPA axis responsivity, even years after they are placed in supportive, well-resourced families. This study examined whether puberty opens a window of opportunity to recalibrate the HPA axis toward more typical reactivity when children shift from harsh deprived conditions in infancy into supportive conditions in childhood and adolescence. Participants (n = 129 postinstitutionalized, 68.2% female; n = 170 comparison, 52.4% female) completed 3 annual sessions beginning at ages 7 to 15 (M = 11.28, SD = 2.31). Each session assessed pubertal stage via nurse examination and cortisol reactivity to the Trier social stress test for children. The linear mixed-effects model controlling for sex and between-individual differences in pubertal stage showed a significant group by pubertal stage interaction: within-individual increases in pubertal stage were associated with increases in cortisol stress reactivity for postinstitutionalized youth but not nonadopted comparison youth. This study indicates that pubertal development reopens a window of opportunity for the HPA axis to recalibrate based on significant improvements in the supportiveness of the environment relative to that in infancy. The peripubertal period may be an important time in development where the caregiving environment has a substantial impact on the HPA axis and, perhaps, other stress-mediating systems. Future research is needed to examine the mechanisms of recalibration and whether HPA recalibration impacts physical and psychological health.
Author contributions: M.R.G. and B.D. designed research; C.E.D., B.M.R., and B.D. performed research; C.E.D. analyzed data; M.R.G. and C.E.D. wrote the paper; and B.M.R. edited paper and assisted with data analysis.
The authors declare no competing interest.
This article is a PNAS Direct Submission. I.H.G. is a guest editor invited by the Editorial Board.
Data deposition: The data from this manuscript are available at https://github.com/cdepasquale/Gunnar-DePasquale-Reid-Donzella-2019-PNAS.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1909699116/-/DCSupplemental.
Published under the PNAS license.
