LONG TERM NEUROBIOLOGICAL IMPACT OF EARLY DEPRIVATION: IMAGING YOUNG ADULT BRAIN STRUCTURE AND FUNCTION IN THE ENGLISH AND ROMANIAN ADOPTEES STUDY.

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Animal research shows that early life adversity has long-term consequences for brain development that increase risk of poor outcome in adulthood. Understanding these processes can, in principle, guide advances in the care of individuals with difficult early life experiences, but real progress depends on parallel research on early adversity in humans. If the ethical difficulties surrounding such work could be overcome, it would become possible to test neurobiological models derived from animal research in humans and evaluate clinical interventions resulting from them. In fact, a unique and serendipitous opportunity to do exactly this is afforded by the large-scale adoption to the UK of children who spent their early years in the Romanian orphanages of the 1980s. These adoptions have created a powerful and ethical natural experiment that allows the effect of exposure to early adversity to be isolated, and thus to examine its impact on brain development. We are leading The English & Romanian Adoptees Study (ERA), the largest developmental study of this cohort, now reaching adulthood. Insights into the effect of early global deprivation from ERA include; (a) a devastating initial impact; (b) a link between adjustment and deprivation duration; (c) remarkable catch-up for most individuals, but marked residual deprivation-linked problems for some (e.g., quasi-autism; ADHD); (d) adolescent onset emotional problems; (g) a mediating role for socio-cognitive and brain processes; (h) moderation of outcomes by genetic factors. Currently, with ESRC support, we are building rich longitudinal dataset on psychosocial adjustment during transition to early adult life. The proposed research will use imaging to gain deeper understanding of the neurobiological processes underlying this adjustment. We are already collecting clinical and biological data relevant to this goal, and an imaging pilot study has been conducted to provide proof of method. We will use state-of-the-art MRI facilities and structural and functional techniques to examine deprivation-related alterations in four adversity-sensitive brain networks implicated in; the processing of positive/negative experiences; executive control; and interpersonal perception. We will compare the functioning of (a) the Romanian Adoptees (total N=165); (b) a UK-adopted comparison group (total N=52); (c) a non-adopted, non-deprived control group (N=35); and (d) two groups of non-adopted/non-deprived clinical (Autism and ADHD) controls (both N=35). fMRI analysis will focus on activation generated by four experimental tasks that map directly on to the four networks: An incentive delay test of responses to monetary gain and loss; an emotional face processing test of responses to positive and negative social cues; a stop signal test of inhibitory control; and an empathic accuracy test of interpersonal information processing. T-1 weighted and diffusion tensor imaging will also be used to examine structural differences between groups, including volumes of key network regions, cortical thickness and folding, and white matter connectivity within and between networks. We will compare structural and functional data across groups and relate our measures to both extent of deprivation and more recent longitudinal data. We can thus explore the neural basis of individual variation in the effects of deprivation on behavioural and clinical outcomes; that is, resilience to, and recovery from, extreme early adversity. Furthermore, we will disentangle the effects of deprivation and co-morbid psychopathology by comparing neural data from clinically referred controls with Autism or ADHD with data from the corresponding deprivation-related phenotypes. Finally our biological sample database will allow us to examine whether (a) genetic factors moderate the effects of deprivation on brain development, and (b) the effects of deprivation are mediated by changes in the brain networks controlling stress reactivity.