Date of Award

Spring 5-15-2015

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Neurosciences)

Degree Name

Doctor of Philosophy (PhD)

Degree Type



Internalizing psychopathology has been linked to increased cortisol reactivity and alterations in limbic brain structure and function, yet the mechanisms underlying these alterations are unclear. One key hypothesis is that stress plays a major causal role in these mechanisms. Animal studies find that chronic stress or glucocorticoid administration lead to alterations in hippocampal and amygdala structure and function. Relatedly, life stress is a major risk factors for depression while candidate gene studies have related variation in hypothalamic-pituitary-adrenal (HPA) axis genes to increased prevalence and severity of depression. The present work tested the hypothesis that genetic profile scores combining variance across 10 single nucleotide polymorphisms from four HPA axis genes (CRHR1, NR3C2, NR3C1, FKBP5) and early life stress would predict increases in stress cortisol levels in preschool-age children as well as alterations in hippocampal and amygdala volumes, reactivity, and resting state functional connectivity in these same children at school age. The current results indicate that (1) childhood stress exposure and genetic profile scores both predict stress cortisol, (2) these factors interact to predict volumetric alterations, partially mediated by cortisol, (3) life stress predicts left amygdala reactivity while genetic profile scores interact with sex and pubertal status to predict amygdala and hippocampus reactivity to negative emotional stimuli, and (4) these factors and their interaction predict weakened amygdala functional connectivity with subcortical and prefrontal regions. Overall, these findings suggest a key role for stress exposure, genetic risk, and cortisol in contributing to individual differences in amygdala and hippocampus structure and function typically associated with internalizing pathology.


English (en)

Chair and Committee

Deanna M Barch

Committee Members

Joan L Luby, Ryan Bogdan, Arpana Agrawal, Tamara Hershey


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