Development and Psychopathology


Influence of early life stress on later hypothalamic–pituitary–adrenal axis functioning and its covariation with mental health symptoms: A study of the allostatic process from childhood into adolescence

Marilyn J. Essexa1 c1, Elizabeth A. Shirtcliffa2, Linnea R. Burka1a3, Paula L. Ruttlea1, Marjorie H. Kleina1, Marcia J. Slatterya1, Ned H. Kalina1 and Jeffrey M. Armstronga1

a1 University of Wisconsin School of Medicine and Public Health

a2 University of New Orleans

a3 University of Wisconsin–Madison


The hypothalamic–pituitary–adrenal (HPA) axis is a primary mechanism in the allostatic process through which early life stress (ELS) contributes to disease. Studies of the influence of ELS on children's HPA axis functioning have yielded inconsistent findings. To address this issue, the present study considers multiple types of ELS (maternal depression, paternal depression, and family expressed anger), mental health symptoms, and two components of HPA functioning (traitlike and epoch-specific activity) in a long-term prospective community study of 357 children. ELS was assessed during the infancy and preschool periods; mental health symptoms and cortisol were assessed at child ages 9, 11, 13, and 15 years. A three-level hierarchical linear model addressed questions regarding the influences of ELS on HPA functioning and its covariation with mental health symptoms. ELS influenced traitlike cortisol level and slope, with both hyper- and hypoarousal evident depending on type of ELS. Further, type(s) of ELS influenced covariation of epoch-specific HPA functioning and mental health symptoms, with a tighter coupling of HPA alterations with symptom severity among children exposed previously to ELS. Results highlight the importance of examining multiple types of ELS and dynamic HPA functioning in order to capture the allostatic process unfolding across the transition into adolescence.

(Online publication October 21 2011)


c1 Address correspondence and reprint requests to: Marilyn J. Essex, Department of Psychiatry, University of Wisconsin School of Medicine and Public Health, 6001 Research Park Boulevard, Madison, WI 53719-1176; E-mail:


This research was supported by NIH Grants R01-MH044340, P50-MH052354, P50-MH069315, and P50-MH084051; the HealthEmotions Research Institute; and the John D. and Catherine T. MacArthur Foundation Research Network on Psychopathology and Development. Support was provided by Career Development Award K01-MH077687 (to E.A.S.) and 1UL1RR025011 (to M.J.S.).