Stress coping changes the brain [electronic resource]

Exposure to stress is a risk factor for the development of subsequent mental illness. Far less researched, but of equal importance, are indications that coping with stressors that are challenging but not overwhelming may lead to the development of resilience. Coping appears to counteract the deleterious effects of stress and is thought to induce long-lasting adaptations in corticolimbic brain systems. My research tests this hypothesis in a series of inter-related studies. First, I considered how learning as an aspect of coping in the context of stress exposure psychotherapy changes the human brain. I conducted a systematic review of the literature and identified 15 brain imaging studies in which human patients with specific phobias or posttraumatic stress disorder were randomized to stress exposure psychotherapies that effectively diminished subsequent indications of anxiety. Exposure psychotherapies also consistently changed amygdala activity in four of the studies. Less consistent prefrontal changes were reported in seven different studies. In contrast to these studies of functional changes in brain activity, only one study was designed to look for structural changes in the brain. Whether stress coping alone is sufficient to induce prefrontal and amygdala adaptations is also not known as coping in the context of stress exposure psychotherapy in several of the studies included additional professional training to enhance cognitive restructuring, relaxation, guided mastery, and diverse forms of psychoeducation. Practical limitations and ethical concerns restrict opportunities for randomized controlled trials of stress coping effects on the human brain. Therefore, I studied a monkey model to determine whether stress coping experiences that occur early in life without additional interventions induce long-lasting adaptations in amygdala and prefrontal brain regions. Using in vivo structural neuroimaging and a randomized longitudinal approach, I found that prefrontal gray matter volumes decrease more at older ages than total brain volumes with less of a decrease observed in monkeys exposed to early life stress coping compared to no stress coping controls. These findings suggest that stress coping produces a brain-reserve that lessens the impact of subsequent normal age-related prefrontal gray matter decline. Stress coping had no effect on amygdala volumes across life-span development, but whole brain exploratory voxel-based morphometry revealed larger ventral striatum gray matter volumes in stress coping compared to no stress coping control monkeys at both 3 and 9 years of age. In a previously published study, stress coping effects were also observed in prefrontal white matter at 3 years of age, but prefrontal white matter volume treatment effects were not discerned in my study at any age. A possible explanation for this discrepancy is the use of diffusion tensor brain imaging in the previously published study to provide a more sensitive measure of white matter myelination. To determine whether stress coping-induced white matter differences previously observed at 3 years of age extend into adulthood, I used diffusion tensor imaging combined with tract-based spatial statistics in the same cohort of monkeys at 9 years of age. Tract-based spatial statistics localized significantly increased fractional anisotropy in bilateral uncinate fasciculus and right external capsule of stress coping compared to no stress coping control animals. Stress coping had no effect on fractional anisotropy in prefrontal white matter regions previously identified at 3 years of age. These data suggest that stress coping induces temporal dynamic prefrontal white matter microstructural changes together with long-lasting increased white matter tract integrity between frontal and limbic regions. Collectively, these studies deepen our understanding of stress neurobiology. According to the World Health Organization, stress will be the second leading cause of all medical disabilities by the year 2020. The American Institute of Stress has determined that 75-90% of medical visits are stress-related and may cost the nation more than 42 billion dollars each year. My research provides neurobiological insights for the development of diagnostic tools and therapeutics that mimic or enhance stress coping and recovery from stress-related mental illness.

Advisor: Lyons David (David Michael) primary advisor. Thesis advisor
Greicius Michael D. advisor. Thesis advisor
Moseley Michael E. (Michael Eugene)
Zeitzer Jamie Marc