Rates of depressive symptoms and diagnoses rise markedly between ages 15-18. Despite the scientific and public health significance, the mechanisms responsible for the adolescent surge in depression are not fully understood. Cognitive vulnerability - stress models have contributed importantly to our understanding of the increased incidence of depression in adolescence;however, these models do not adequately explain some of the somatic symptoms or incorporate biological stress mechanisms through which cognitive vulnerability evokes depression. A separate exciting body of research on immune correlates of depression has highlighted the role of proinflammatory pathways;yet, only some depressed individuals exhibit inflammation. This project provides a novel and compelling integration of the cognitive vulnerability - stress framework and the proinflammatory model of depression as applied to adolescence. The research has the potential to solve puzzles and limitations faced by both models when considered separately. The findings may help to account for the full spectrum of depressive symptoms and identify cognitively vulnerable individuals as especially likely to evince signs of cytokine dysregulation and increased reactivity to stressful events. Moreover, it is known that early childhood adversity contributes to both the development of cognitive vulnerability and a proinflammatory bias. The primary goal is to determine the role of inflammatory states in combination with cognitive vulnerabilities, stress, and childhood adversity as contributors that underlie the rise in adolescent depression. A multiwave, 4-year prospective study will be conducted with an existing, well-characterized community sample of 300 adolescents, including similar numbers of males and females and Caucasians and African-Americans, just reaching the critical age when the dramatic rise in depression begins. We will conduct yearly blood draws to assess proinflammatory and regulatory cytokines (a multicytokine array of 7 cytokines) and C-reactive protein (CRP), in parallel with ongoing assessments of life stress and depression and anxiety symptoms every 6 months. Cognitive vulnerabilities and depression and anxiety diagnoses will be obtained yearly, along with a history of childhood adversity in this unique cohort of urban adolescents. We also will examine interleukin-6 (IL- 6) reactivity to an acute stressor (Trier Social Stress Test) to determine how individual variation in cognitive reactivity translates into increased IL-6 release. This project fills a crucial knowledge gap about normal development of immunity in adolescence and its role in the dramatic rise in adolescent depression. It may lead to novel interventions for depression that target cognitive influences on cytokine responses to stress, as well as pharmacological manipulations of cytokines to address symptoms such as fatigue, anhedonia, and withdrawal.

Public Health Relevance

Knowledge of mechanisms that lead to depression in adolescence is important to refine interventions to treat or prevent this prevalent condition before it undermines educational pursuits, contributes to alcohol or drug use, and becomes a lifelong problem in adulthood. The proposed prospective study will investigate the role of inflammatory states (cytokine biology) in response to stress in combination with cognitive vulnerabilities and childhood adversity as contributors underlying the rise in adolescent depression. The knowledge gained will help develop novel interventions for depression that target cognitive influences on inflammatory responses to stress, as well as highlight the value of pharmacological manipulations of cytokines to address depression.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
Project #
Application #
Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Garriock, Holly A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Temple University
Schools of Arts and Sciences
United States
Zip Code
Hamlat, Elissa J; Connolly, Samantha L; Hamilton, Jessica L et al. (2015) Rumination and overgeneral autobiographical memory in adolescents: an integration of cognitive vulnerabilities to depression. J Youth Adolesc 44:806-18
Wagner, Clara A; Alloy, Lauren B; Abramson, Lyn Y (2015) Trait rumination, depression, and executive functions in early adolescence. J Youth Adolesc 44:18-36
Hamilton, Jessica L; Connolly, Samantha L; Liu, Richard T et al. (2015) It gets better: future orientation buffers the development of hopelessness and depressive symptoms following emotional victimization during early adolescence. J Abnorm Child Psychol 43:465-74
Shapero, Benjamin G; Black, Shimrit K; Liu, Richard T et al. (2014) Stressful life events and depression symptoms: the effect of childhood emotional abuse on stress reactivity. J Clin Psychol 70:209-23
Liu, Richard T; Alloy, Lauren B; Mastin, Becky M et al. (2014) Vulnerability-specific stress generation: an examination of depressogenic cognitive vulnerability across multiple domains. Anxiety Stress Coping 27:695-711
Kleiman, Evan M; Riskind, John H; Stange, Jonathan P et al. (2014) Cognitive and interpersonal vulnerability to suicidal ideation: a weakest link approach. Behav Ther 45:778-90
Liu, Richard T; Kraines, Morganne A; Massing-Schaffer, Maya et al. (2014) Rejection sensitivity and depression: mediation by stress generation. Psychiatry 77:86-97
Connolly, Samantha L; Wagner, Clara A; Shapero, Benjamin G et al. (2014) Rumination prospectively predicts executive functioning impairments in adolescents. J Behav Ther Exp Psychiatry 45:46-56
Hamlat, Elissa J; Stange, Jonathan P; Abramson, Lyn Y et al. (2014) Early pubertal timing as a vulnerability to depression symptoms: differential effects of race and sex. J Abnorm Child Psychol 42:527-38
Stange, Jonathan P; Hamilton, Jessica L; Abramson, Lyn Y et al. (2014) A vulnerability-stress examination of response styles theory in adolescence: stressors, sex differences, and symptom specificity. J Clin Child Adolesc Psychol 43:813-27

Showing the most recent 10 out of 11 publications