Early institutional deprivation has been linked to a complex pattern of neurodevelopmental problems – aspects of which persist into adulthood, yet its impact on brain structure is currently unknown. This thesis investigates how early childhood institutional deprivation impacts adult brain structure and structural covariance. Structural magnetic resonance imaging data were acquired in a group of young adults who had been exposed to severe institutional deprivation during the Ceaușescu era in Romania before being adopted into nurturing families in early childhood. This prospective natural experiment is a powerful design because it allows the specific effects of early adversity on brain development and disorder to be studied independently of non-deprivation-related risks and familial genetic confounds which often limit the ability to draw causal inferences in non-prospective studies of maltreatment occurring within biological families. Sixty-seven Romanian adoptees, who had experienced between 3 and 41 months of institutional deprivation, were compared to 21 non-deprived UK adoptees. Data were analysed using surface-based morphometry methods. Institutional deprivation in early childhood was associated with substantially smaller total brain volumes in young adulthood reflected in a dose-dependent negative association with deprivation duration. Above and beyond this global effect, institutionalisation was associated with a number of distinct regional changes. There was relatively larger cortical surface area, thickness and volume in the right inferior temporal cortex and relatively smaller surface area and volume in the right inferior frontal cortex following institutionalisation. Deprivation duration was positively associated with surface area and volume in right anterior cingulate cortex/ medial orbitofrontal cortex. There were no effects of deprivation on subcortical structures including amygdala and hippocampus after correction for total brain volume. When we tested for brain-behaviour relationships, a range of patterns were observed: Smaller brain volume was associated with increased risk of disinhibited social engagement symptoms and low IQ. In contrast, deprivation-related alterations of the right inferior frontal and temporal cortices were related to more effective proactive inhibition and better prospective memory and fewer ADHD symptoms, respectively - suggestive of neural compensation of either a latent (affecting underlying cognitive processes only) or fully manifest nature (reduced risk of disorder symptoms). There was also evidence of deprivation potentially creating latent vulnerability for future disorder with deprivation-related increases in right anterior cingulate volume associated with impaired empathic accuracy. In addition to these effects in regions of interest, on a whole-brain level, deprivation moderated the association between brain structure and symptoms of ADHD, ASD and IQ. Most striking was increased gyrification in those with high levels of ADHD symptoms who had experienced extended deprivation. This provides preliminary evidence that deprivation-related symptoms may have different neurobiological signatures compared to non-deprivation-related symptoms. Early institutional deprivation was also associated with alterations in structural covariance of cortical thickness and surface area with those having experienced more than 6 months deprivation demonstrating both increased as well as decreased correlation strengths between frontal and temporal brain regions with distinct changes for cortical thickness and surface area. These findings stress that deprivation may lead to brain structural alterations which in part reflect changes in coordinated brain network development, with the right fronto-temporal regions being most sensitive to deprivation. Together, these findings provide compelling evidence that early institutional deprivation has strong neurobiological programming effects on brain development. It highlights how early adverse environments during sensitive periods of heightened neuroplasticity in the first few years of life can lead to persistent changes in brain structure that are present in young adulthood, more than 20 years after exposure to adversity has ended.
|Date of Award
|1 Jul 2019
|Edmund Sonuga-Barke (Supervisor) & Mitul Mehta (Supervisor)