The primary aim of this proposal is to investigate the normative development of the neurobiology that results in mental illness associated with emotional difficulties including high reactivity and poor regulation. Such illnesses include, but are not limited to, anxiety, depression, schizophrenia, bipolar disorder, sociopathy, and personality disorders. A failure to effectively recruit a neural circuitry that includes the amygdala and ventromedial prefrontal cortex has been implicated in these mental illnesses in adults. The present research strategy, which uses structural and functional magnetic resonance imaging (MRI) and behavioral measures, will employ a prospective and longitudinal design that identifies biomarkers associated with these difficulties and map their development as children age into adolescence.
The second aim i s to examine the influence of early adverse caregiving environments on the development of this neurobiology. For long, it has been recognized that environmental stress is associated with a disproportionately high of risk emotional psychopathology. A large animal literature combined with an emerging human neuroimaging literature shows that environmental stress can impair mental health functioning via disruption of the amygdala and the regulatory processes that depend on proper connectivity between amygdala and ventromedial prefrontal cortex. When stress exposure occurs prior to developmental maturity, the effects can be more potent and its impact longer lasting than stress that occurs in adulthood. Therefore, the findings of this project will have a high impact on the field of mental health by identifying biomarkers associated with emotional difficulties prior to their behavioral onset. In this way, we will be better at predicting and preventing the development of mental illnesses that often emerge during the adolescent period.

Public Health Relevance

This project will examine the development of a specific neurobiology that is associated with emotional difficulties such as high reactivity and poor regulation. In addition to mapping out the typical development of this biology, this project will examine the role that adverse early caregiving has on its development. This research is important because identification of biomarkers during development before they emerge into problem behaviors in adulthood will help in the prevention of mental illnesses associated with emotional difficulties.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Application #
Study Section
Special Emphasis Panel (ZMH1-ERB-L (04))
Program Officer
Zehr, Julia L
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University of California Los Angeles
Schools of Arts and Sciences
Los Angeles
United States
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VanTieghem, Michelle R; Tottenham, Nim (2018) Neurobiological Programming of Early Life Stress: Functional Development of Amygdala-Prefrontal Circuitry and Vulnerability for Stress-Related Psychopathology. Curr Top Behav Neurosci 38:117-136
Humphreys, Kathryn L; Gabard-Durnam, Laurel; Goff, Bonnie et al. (2018) Friendship and social functioning following early institutional rearing: The role of ADHD symptoms. Dev Psychopathol :1-11
Fareri, Dominic S; Gabard-Durnam, Laurel; Goff, Bonnie et al. (2017) Altered ventral striatal-medial prefrontal cortex resting-state connectivity mediates adolescent social problems after early institutional care. Dev Psychopathol 29:1865-1876
Flannery, Jessica E; Gabard-Durnam, Laurel J; Shapiro, Mor et al. (2017) Diurnal cortisol after early institutional care-Age matters. Dev Cogn Neurosci 25:160-166
Silvers, Jennifer A; Goff, Bonnie; Gabard-Durnam, Laurel J et al. (2017) Vigilance, the Amygdala, and Anxiety in Youths with a History of Institutional Care. Biol Psychiatry Cogn Neurosci Neuroimaging 2:493-501
Tottenham, Nim; Gabard-Durnam, Laurel J (2017) The developing amygdala: a student of the world and a teacher of the cortex. Curr Opin Psychol 17:55-60
Fareri, Dominic S; Tottenham, Nim (2016) Effects of early life stress on amygdala and striatal development. Dev Cogn Neurosci 19:233-47
Callaghan, Bridget L; Tottenham, Nim (2016) The Stress Acceleration Hypothesis: Effects of early-life adversity on emotion circuits and behavior. Curr Opin Behav Sci 7:76-81
Humphreys, Kathryn L; Telzer, Eva H; Flannery, Jessica et al. (2016) Risky decision making from childhood through adulthood: Contributions of learning and sensitivity to negative feedback. Emotion 16:101-9
Gabard-Durnam, Laurel Joy; Gee, Dylan Grace; Goff, Bonnie et al. (2016) Stimulus-Elicited Connectivity Influences Resting-State Connectivity Years Later in Human Development: A Prospective Study. J Neurosci 36:4771-84

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