AbstractThe biological mechanisms through which childhood physical and sexual abuse increase the risk of psychosis are unclear. This thesis investigated the presence of abnormalities in brain structure and in the hypothalamic-pituitary-adrenal (HPA) axis activity in people at their first episode of psychosis (FEP) and controls, with and without a history of childhood abuse.
Structural MRI scans were acquired in 86 FEP patients (49 abuse positive) 64 controls (30 abuse positive). The HPA axis was evaluated in 169 FEP (110 abuse positive) and 133 controls (67 abuse positive). In this population I explored differences in grey matter volume and cortical thickness and cortisol concentrations during the day and at awakening in association with abuse exposure. Finally I correlated cortisol levels with cortical thickness in regions sensitive to abuse.
Childhood abuse was associated with smaller grey matter volume and reduced cortical thickness in frontal and occipital brain regions. I found an interaction between psychosis and abuse in frontal and parietal regions, which had greater grey matter volume and cortical thickness in controls and smaller in FEP exposed to childhood abuse. There was an interaction between psychosis and abuse in the cortisol awakening response (CARg) as FEP exposed to severe childhood abuse showed a blunted CARg while controls exposed to severe abuse had higher CARg. Finally there was a negative correlation between cortisol and cortical thickness: larger thickness in brain frontal and parietal regions sensitive to abuse exposure were correlated with lower cortisol levels during the day in controls but not in FEP.
Childhood abuse has a differential impact on the brain structure as well as the HPA axis activity in FEP and controls. The relationship between cortisol and cortical thickness in regions sensitive to abuse found only in controls suggests an integration of brain structure and HPA axis activity and possibly an adaptive mechanism to environmental stress.
|Date of Award||2018|
|Supervisor||Paola Dazzan (Supervisor), Valeria Mondelli (Supervisor) & Matthew Kempton (Supervisor)|