Risk for Adolescent Depression: Stress, Cognitive Vulnerability, &Inflammation

Summary

Principal Investigator: LAUREN BERSH ALLOY
Abstract: DESCRIPTION (provided by applicant): 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.
Funding Period: 2013-07-01 - 2018-06-30
more information: NIH RePORT

Top Publications

  1. ncbi Vulnerability-specific stress generation: an examination of depressogenic cognitive vulnerability across multiple domains
    Richard T Liu
    a Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA
    Anxiety Stress Coping 27:695-711. 2014

Detail Information

Publications4

  1. ncbi Vulnerability-specific stress generation: an examination of depressogenic cognitive vulnerability across multiple domains
    Richard T Liu
    a Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, RI, USA
    Anxiety Stress Coping 27:695-711. 2014
    ..This extension was tested within the context of Cole's competency-based model of depression...

Research Grants30

  1. Hopkins Center for Eliminate Cardiovascular Health Disparities
    Lisa A Cooper; Fiscal Year: 2013
    ..abstract_text> ..
  2. Neurobiological Reactivity, Allostatic Load and Depression in Mexican Youth
    PAUL DAVID HASTINGS; Fiscal Year: 2013
    ..Consequently, this will be one of the only prospective longitudinal studies of allostatic load as a mechanism of the development of depression in Mexican-origin adolescents. ..
  3. Prepubertal Stress, Windows of Risk &Sex Bias for Affective Disturbance
    C NEILL NEILL EPPERSON; Fiscal Year: 2013
    ..The Center would provide an intellectual platform with important resources to encourage established investigators, and their mentees, to consider sex and gender as crucial factors in their research. ..
  4. Prostate Cancer Bone Metastasis: Biology and Targeting
    Leland W K Chung; Fiscal Year: 2013
    ..abstract_text> ..
  5. Mechanisms of Risk and Resilience in ASD: Ontogeny, Phylogeny and Gene Disruption
    Ami Klin; Fiscal Year: 2013
    ..abstract_text> ..
  6. CENTER FOR CHILD ENVIRONMENTAL HEALTH RISKS RESEARCH
    Elaine M Faustman; Fiscal Year: 2013
    ..The Center also includes junior investigators, new scientists since the 2003 Center renewal, and a Faculty Development Investigator. The Internal Steering Committee in comprised of a number of Center investigators and directors. ..
  7. Imaging Brain, Neurocognitive and Pubertal Maturation During Adolescence
    Elizabeth R Sowell; Fiscal Year: 2013
    ....
  8. Mental Stress and Myocardial Ischemia after MI: Sex Differences and Mechanisms
    Viola Vaccarino; Fiscal Year: 2013
    ..Investigation of this group will provide critical information for the pathophysiology and prevention of ischemic heart disease in women. ..
  9. Temperamental Emotionality in Preschoolers and Depression Risk
    Daniel N Klein; Fiscal Year: 2013
    ..This will contribute to understanding when and how to intervene in order to prevent the disorder and/or its progression. ..
  10. Changes in brain function during adolescence and risk for depression in girls
    KATHRYN ELIZABETH KEENAN; Fiscal Year: 2013
    ....
  11. Notch-Mediated Expansion of Cord Blood Progenitors for Stem Cell Transplant
    Colleen Delaney; Fiscal Year: 2013
    ..Our goal is to now determine the clinical efficacy of this approach in a phase II clinical trial. ..
  12. VCU NIMHD Comprehensive Center of Excellence
    Jerome F Strauss; Fiscal Year: 2013
    ..abstract_text> ..
  13. Center for the Neurobiology of Addiction Treatment
    Steven R Childers; Fiscal Year: 2013
    ..These projects utilize several animal models and technologies uniquely developed by the Center investigators over the previous years of its funding history. ..
  14. Vulnerability to Drug Abuse:Pathways to Recovery
    Elizabeth Jane Costello; Fiscal Year: 2013
    ..H3. Stable recovery vs. relapse will be associated with poor delay of gratification and high sensation seeking. H4. Despite higher levels of SUD in Indians and males, neurocognitive mechanisms of risk will not differ. ..
  15. Comprehensive NeuroAIDS Core Center
    Kamel Khalili; Fiscal Year: 2013
    ..abstract_text> ..
  16. Risk Genes and Environment Interactions in NTDs
    MARGARET ELIZABETH ROSS; Fiscal Year: 2013
    ..Progress made for this disorder can provide useful analytical tools for identifying molecular network interactions relevant to later-onset complex genetic disorders, like schizophrenia and autism. ..
  17. Intergenerational Transmission of Risk for Drug Use
    Terence P Thornberry; Fiscal Year: 2013
    ....
  18. Violence Exposure, Immune Function &HIV/AIDS Risks in African American Young Ad
    FROUGH SAADATMAND; Fiscal Year: 2013
    ..abstract_text> ..