Doctor of Philosophy
Morton, J Bruce
Individuals exposed to adversities in childhood are at a greater risk of developing various diseases as adults, including cardiovascular disease and cancer (Felitti et al. 1998). These findings have sparked an interest in examining biological mechanisms that might explain the link between exposure to adversity and disease. To date, evidence has linked adversity to the function of the hypothalamic-pituitary-adrenal (HPA) axis. More recently, adversity has been associated with the function of the mesolimbic dopamine pathway as well.
This thesis uses a variety of techniques to explore the association between adversity and the function of the HPA axis and mesolimbic dopamine pathway. Current evidence examining exposure to adversity and the function of the HPA axis and mesolimbic dopamine pathway remains highly contradictory—with some studies reporting heightened cortisol and dopamine reactivity, and others reporting blunted reactivity. I hypothesized that the mixed findings may be related to inconsistent definitions of what constitutes “adversity”. The term “adversity” is typically used broadly and ranges from moderate stressors (e.g., work-related stress) to extremely traumatic events (e.g., sexual abuse). This thesis makes a clear distinction between trauma and adversity to help resolve the apparent contradictions in the literature.
In Chapter 2, p-curve meta-analysis was used to explore the literature linking trauma versus adversity to cortisol reactivity. The results provided support for associations between trauma and blunted cortisol reactivity, and moderate adversity and heightened cortisol reactivity.
In Chapter 3, a systematic review of the human Positron Emission Tomography (PET) imaging studies was conducted to examine the relationships between adversity versus trauma and dopamine reactivity. The results mirror the findings from Chapter 2, demonstrating that trauma is associated with blunted dopamine reactivity, while adversity is associated with heightened dopamine reactivity.
Chapter 4 uses behavioural and functional magnetic resonance imagining (fMRI) methods to explore the link between adversity, impulsivity, reward-learning, and ventral striatal reactivity to rewards. The findings demonstrate that adversity is associated with impulsivity, potentiated reward-learning, and that the association between adversity and reward-learning was partially mediated by ventral striatal reactivity. Overall, these findings support an inverted U-shaped relationship between severity of adversity and cortisol and dopamine reactivity.
Summary for Lay Audience
Do adverse life-experiences leave a lasting imprint on the brain? Likewise, does experiencing adversity have consequences for health and well-being? Seminal work by Felitti and colleagues (1998) showed that individuals exposed to adversities in childhood are at a greater risk of developing various diseases as adults, including heart disease and cancer. As a result of these findings, researchers began investigating how adversity becomes “biologically embedded into the brain”. To date, evidence has linked adversity to the function of two neural systems:
1.) the hypothalamic-pituitary-adrenal (HPA) axis involved in stress responses and cortisol secretion
2.) the dopamine pathway involved in reward-learning and decision-making
This thesis addressed how adverse life-experiences are related to the function of the HPA axis and dopamine pathway. There is a wealth of data showing that adversity is related to differences in the function of the HPA axis and dopamine pathway, but what is unclear, is if adversity is related to heightened cortisol and dopamine levels, or reduced cortisol and dopamine levels. One reason for the mixed findings is that the term “adversity” is broad and can range from moderate stressors (e.g., work-related stress) to extreme trauma (e.g., sexual abuse). Here, I differentiated between moderate adversity and extreme trauma and I examined how each is related to differences in the function of the HPA axis and dopamine pathway. In Chapter 2, I examined how adversity and trauma are related to cortisol function, and I found that trauma was related to reduced cortisol reactivity, while adversity was related to heightened cortisol reactivity. Chapter 3 investigated the link between adversity and trauma and the dopamine pathway; like the findings in Chapter 2, I found that adversity was related to heightened dopamine levels, while trauma was related to reduced dopamine levels. Finally, in Chapter 4, 9-12-year-old children participated in a neuroimaging study and we obtained measures of adversity from their parents. The results showed that children who experienced more adversity were more impulsive, learned faster from rewards, and the reward regions within the dopamine pathway reacted more to receiving rewards compared to children who had experienced less adversity.
Hosseini-Kamkar, Niki, "Early experience and the functional calibration of the stress-response systems" (2021). Electronic Thesis and Dissertation Repository. 8252.
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