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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
4R01MH101168-04
Application #
9085390
Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Murphy, Eric Rousseau
Project Start
2013-07-01
Project End
2018-03-31
Budget Start
2016-04-01
Budget End
2017-03-31
Support Year
4
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Temple University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
057123192
City
Philadelphia
State
PA
Country
United States
Zip Code
19122
Stange, Jonathan P; Hamilton, Jessica L; Fresco, David M et al. (2017) Perseverate or decenter? Differential effects of metacognition on the relationship between parasympathetic inflexibility and symptoms of depression in a multi-wave study. Behav Res Ther 97:123-133
Stange, Jonathan P; Hamilton, Jessica L; Fresco, David M et al. (2017) Flexible parasympathetic responses to sadness facilitate spontaneous affect regulation. Psychophysiology 54:1054-1069
Stange, Jonathan P; Alloy, Lauren B; Fresco, David M (2017) Inflexibility as a Vulnerability to Depression: A Systematic Qualitative Review. Clin Psychol (New York) 24:245-276
Jessar, Allison J; Hamilton, Jessica L; Flynn, Megan et al. (2017) Emotional Clarity as a Mechanism Linking Emotional Neglect and Depressive Symptoms during Early Adolescence. J Early Adolesc 37:414-432
Shapero, Benjamin G; McClung, George; Bangasser, Debra A et al. (2017) Interaction of Biological Stress Recovery and Cognitive Vulnerability for Depression in Adolescence. J Youth Adolesc 46:91-103
Kleiman, Evan M; Chiara, Alexandra M; Liu, Richard T et al. (2017) Optimism and well-being: a prospective multi-method and multi-dimensional examination of optimism as a resilience factor following the occurrence of stressful life events. Cogn Emot 31:269-283
Connolly, Samantha L; Alloy, Lauren B (2017) Rumination interacts with life stress to predict depressive symptoms: An ecological momentary assessment study. Behav Res Ther 97:86-95
Mac Giollabhui, Naoise; Hamilton, Jessica L; Nielsen, Johanna et al. (2017) Negative Cognitive Style Interacts With Negative Life Events to Predict First Onset of a Major Depressive Episode in Adolescence via Hopelessness. J Abnorm Psychol :
Hamilton, Jessica L; Alloy, Lauren B (2017) Physiological Markers of Interpersonal Stress Generation in Depression. Clin Psychol Sci 5:911-929
Daryanani, Issar; Hamilton, Jessica L; McArthur, Brae Anne et al. (2017) Cognitive Vulnerabilities to Depression for Adolescents in Single-Mother and Two-Parent Families. J Youth Adolesc 46:213-227

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