Early experience and the functional calibration of the stress-response systems
Abstract
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.