Childhood adversity exposure is linked to recurrent and treatment resistant depression across the lifespan. Childhood adversity is also associated with exaggerated inflammatory responses to stress. Acute inflammatory responses can induce the behavioral phenotype for depression, including reduced motivation for rewards and enhanced sensitivity to threat. In this study, we aim to determine the association between childhood adversity and behavioral responses to acute psychological stress. We also aim to characterize the association between childhood adversity and inflammatory responses to stress. Finally, we aim to test whether the magnitude of inflammatory responses to acute stress mediate the behavioral response to threat. We hypothesize that youth exposed to childhood adversity will demonstrate greater increases in threat sensitivity, reward motivation, and markers of inflammation following acute psychological stress. Further, we hypothesize that inflammatory responses to stress will mediate changes in behavior in response to acute stress. We will recruit a sample of 90 adolescents (ages 12-15) exposed to high (4+ adverse childhood events) and low (0-3 adverse childhood events) adversity. During a laboratory visit, youth will complete several behavioral measures of reward motivation and threat sensitivity, participate in an acute psychological stress paradigm (TSST-C), and then complete measures of reward motivation and threat sensitivity 60 minutes after stress initiation. Throughout this laboratory assessment, we will collect blood and saliva to measure systemic, cellular, and intracellular markers of inflammation. We anticipate that data from this study will support our hypothesis that childhood adversity is associated with exaggerated behavioral and inflammatory responses to stress. Completion of this study will identify three modifiable risk factors (threat sensitivity, reward motivation, inflammation) for depression in at risk youth, and support a program of research examining cognitive and behavioral strategies that may mitigate these effects.

Public Health Relevance

Exposure to adversity during childhood contributes significantly to the burden of mental health in the United States. This project seeks to identify modifiable behavioral and biological risk factors that may inform our understanding of how stress leads to depression and mitigate the lifelong negative health sequelae of childhood adversity exposure.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Clinical Investigator Award (CIA) (K08)
Project #
1K08MH112773-01
Application #
9291816
Study Section
Child Psychopathology and Developmental Disabilities Study Section (CPDD)
Program Officer
Sarampote, Christopher S
Project Start
2017-08-01
Project End
2022-07-31
Budget Start
2017-08-01
Budget End
2018-07-31
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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