The transition through adolescence is characterized by a striking increase in symptoms and rates of depression. In fact, the majority of first episodes of MDD occur during adolescence. One-quarter of adolescents experience an episode of Major Depressive Disorder (MDD) by the end of their teenage years, and almost half of adolescents with a depressive episode experience a recurrence within three years. In attempting to identify factors that contribute to this high prevalence of depression in adolescence, investigators have focused on the adverse effects of exposure to stress occurring during childhood, or early life stress (ELS). ELS, including abuse, neglect, parental loss, and interpersonal stress, is associated with a marked increase in risk for subsequent depression. We do not yet understand, however, the mechanisms by which ELS contributes to this risk, thus hampering effective prevention and intervention efforts with adolescents. The proposed project is designed to examine trajectories of two psychobiological mechanisms that may explain how ELS increases risk for depression during adolescence: increased stress reactivity and blunted reward sensitivity. This focus on the trajectories of stress and reward systems is particularly salient in adolescence given that both of these systems undergo significant change and reorganization during this sensitive period of development. We propose to follow longitudinally 220 boys and girls who have already completed two comprehensive assessments (beginning at 9 to 12 years of age), two years apart, of their exposure to ELS, psychobiological functioning (including behavioral, cognitive, endocrine, and neural assessments of stress reactivity and reward sensitivity), and MDD symptoms and diagnosis. We will leverage data obtained from this large and richly-characterized sample of children to examine prospectively the developmental mechanisms by which ELS affects the onset and course of depression during adolescence. Specifically, we will integrate data from the participants? first two assessments completed in late childhood and early adolescence with new data that we propose to obtain at two additional assessments conducted in mid and late adolescence, a developmental period during which the incidence of MDD peaks. Specifically, we will continue to assess clinical characteristics, information-processing biases, endocrine functioning, and brain function, structure, and connectivity. Collectively, this approach will allow us to analyze the effects of ELS on trajectories of psychobiological and clinical functioning from childhood through late adolescence, and on deviations from normative trajectories of these constructs. Findings from this project will inform efforts to generate personalized targets in order to tailor prevention and treatment programs to adolescents who have been exposed to ELS and who, consequently, are at high risk for developing MDD.

Public Health Relevance

/Public Health Relevance: Although early life stress (ELS) is a significant risk factor for the development of depression during adolescence, the psychobiological mechanisms through which ELS confers this heightened vulnerability are poorly understood. In this project we will test our formulation that exposure to ELS leads to depression during adolescence by altering adolescent-typical trajectories of stress reactivity and reward sensitivity. Findings from this project will inform efforts to generate personalized targets in order to tailor prevention and treatment programs for adolescents who have been exposed to ELS and, consequently, are at high risk for developing depression.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Method to Extend Research in Time (MERIT) Award (R37)
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Psychosocial Development, Risk and Prevention Study Section (PDRP)
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Murphy, Eric Rousseau
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Stanford University
Schools of Arts and Sciences
United States
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Davis, Elena Goetz; Keller, Jennifer; Hallmayer, Joachim et al. (2018) Corticotropin-releasing factor 1 receptor haplotype and cognitive features of major depression. Transl Psychiatry 8:5
Humphreys, Kathryn L; Schouboe, Sophie N F; Kircanski, Katharina et al. (2018) Irritability, Externalizing, and Internalizing Psychopathology in Adolescence: Cross-Sectional and Longitudinal Associations and Moderation by Sex. J Clin Child Adolesc Psychol :1-9
Schwartz, Jaclyn; Ordaz, Sarah J; Ho, Tiffany C et al. (2018) Longitudinal decreases in suicidal ideation are associated with increases in salience network coherence in depressed adolescents. J Affect Disord 245:545-552
Ordaz, Sarah J; Goyer, Meghan S; Ho, Tiffany C et al. (2018) Network basis of suicidal ideation in depressed adolescents. J Affect Disord 226:92-99
Humphreys, Kathryn L; Watts, Emily L; Dennis, Emily L et al. (2018) Stressful Life Events, ADHD Symptoms, and Brain Structure in Early Adolescence. J Abnorm Child Psychol :
Humphreys, Kathryn L; King, Lucy S; Sacchet, Matthew D et al. (2018) Evidence for a Sensitive Period in the Effects of Early Life Stress on Hippocampal Volume. Dev Sci :e12775
Ho, Tiffany C; Cichocki, Anna C; Gifuni, Anthony J et al. (2018) Reduced dorsal striatal gray matter volume predicts implicit suicidal ideation in adolescents. Soc Cogn Affect Neurosci 13:1215-1224