Title: Longitudinal changes in amygdala, hippocampus and cortisol development following early caregiving adversity
Description: Decades of research have shown long-term effects of early caregiving adversity on stress physiology and limbic brain regions, two key biological systems that are implicated in risk for internalizing disorders. Although stress physiology and limbic brain structure undergo significant maturational change during childhood and adolescence, and reciprocally influence each other, the effects of early caregiving adversity on these developmental processes is not well understood. In the current study, we used an accelerated longitudinal design to assess the development of stress physiology, amygdala, and hippocampal volume following early institutional care. Previously Institutionalized (PI; N = 93) and comparison (COMP; N = 161) youth (ages 4-20 years old) completed 1-3 waves of data collection, each spaced approximately 2 years apart, for diurnal cortisol (N = 239, providing a total of 380 diurnal datasets), structural MRI (N = 156, providing a total of 306 scans) and parent-reported internalizing symptoms (N = 133, providing a total of 227 time points).

We observed a developmental shift in morning cortisol in the PI group, with blunted levels in childhood and heightened levels in late adolescence. PI history was associated with reduced hippocampal volume and reduced growth of the amygdala, resulting in smaller volumes by adolescence. Results also suggested feed-forward brain-to-hormone mechanisms, such that both amygdala and hippocampal volumes were prospectively associated with morning cortisol levels two years later. Finally, amygdala and hippocampal volumes were independently associated with internalizing scores across the entire sample. These results indicate that adversity-related physiological and neural phenotypes are not stationary during development but instead exhibit dynamic and interdependent changes from early childhood to early adulthood.