Adolescence is a period of rapid change, marked by increased stress and emotion regulation difficulties, and concomitant increases in stress-related psychopathology. Although much research has been devoted to understanding the role of stress response systems, especially the HPA axis, in the development and maintenance of internalizing disorders, very little research has focused on the vulnerable adolescent period and none has been conducted prospectively beginning in infancy. Over the past 17 years, a large cohort of children participating since birth in the Wisconsin Study of Family and Work has been intensively studied to examine longitudinal associations of early stress exposure, HPA activity, and the development of childhood mental health problems. Based on these unique developmental data, the present proposal affords an unprecedented opportunity to follow this sample through adolescence, addressing novel questions regarding the role of early stress exposure in the sensitization of the HPA axis to later stress, associations with neural correlates of emotion dysregulation, and the development and course of internalizing psychopathology during this vulnerable period. To extend the existing longitudinal dataset to late adolescence, 300 adolescents and their mothers will be interviewed in grade 12 (approximate age 18). In addition, a,subset of 120 adolescents - selected on high vs. low early (age 41/?) and later (ages 11,13 and 15) cortisol levels - will participate in an intensive laboratory assessment of HPA reactivity and, as part of Projects 4 and 5, neural bases of emotion regulation.
Major aims are 1) to investigate the stress sensitization hypothesis in a community sample experiencing the normative stressors of adolescence;2) to test the stress sensitization hypothesis in a formal laboratory paradigm (the Trier Social Stress Test) with high salience for adolescents; and 3) to identify the stress exposure, HPA, other stress reactivity, and neural circuitry factors, and their combinations, which best discriminate individuals with internalizing disorders by late adolescence. Relevance: This work is highly innovative, integrating the strengths of longitudinal field research with those of laboratory approaches to understand the development of the HPA stress response system and the neural circuitry implicated in adolescent vulnerability to develop stress-related psychopathology, thus providing much needed information for researchers, clinicians, and policymakers.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZMH1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Wisconsin Madison
United States
Zip Code
Amiri, Anahita; Coppola, Gianfilippo; Scuderi, Soraya et al. (2018) Transcriptome and epigenome landscape of human cortical development modeled in organoids. Science 362:
Wang, Daifeng; Liu, Shuang; Warrell, Jonathan et al. (2018) Comprehensive functional genomic resource and integrative model for the human brain. Science 362:
Curtis, David (2018) Polygenic risk score for schizophrenia is not strongly associated with the expression of specific genes or gene sets. Psychiatr Genet 28:59-65
Gandal, Michael J; Haney, Jillian R; Parikshak, Neelroop N et al. (2018) Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap. Science 359:693-697
Curtis, David (2018) Polygenic risk score for schizophrenia is more strongly associated with ancestry than with schizophrenia. Psychiatr Genet 28:85-89
Hilt, Lori M; Armstrong, Jeffrey M; Essex, Marilyn J (2017) Rumination and Moderators of Multifinality: Predicting Internalizing Symptoms and Alcohol Use During Adolescence. J Clin Child Adolesc Psychol 46:746-753
Brooker, Rebecca J; Canen, Mara J; Davidson, Richard J et al. (2017) Short- and long-term stability of alpha asymmetry in infants: Baseline and affective measures. Psychophysiology 54:1100-1109
Planalp, Elizabeth M; Van Hulle, Carol; Lemery-Chalfant, Kathryn et al. (2017) Genetic and environmental contributions to the development of positive affect in infancy. Emotion 17:412-420
Sarkisian, Katherine; Van Hulle, Carol; Lemery-Chalfant, Kathryn et al. (2017) Childhood inhibitory control and adolescent impulsivity and novelty seeking as differential predictors of relational and overt aggression. J Res Pers 67:144-150
Shackman, A J; Fox, A S; Oler, J A et al. (2017) Heightened extended amygdala metabolism following threat characterizes the early phenotypic risk to develop anxiety-related psychopathology. Mol Psychiatry 22:724-732

Showing the most recent 10 out of 134 publications