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

动物研究表明，早期生活中的逆境对大脑发育有长期影响，增加了成年后不良结果的风险。从原则上讲，理解这些过程可以指导对早期生活经历困难的个体的护理进展，但真实的进展取决于对人类早期逆境的平行研究。如果能够克服围绕这类工作的伦理难题，就有可能在人类身上测试从动物研究中得出的神经生物学模型，并评估由此产生的临床干预措施。事实上，一个独特的和偶然的机会，做到这一点是由大规模收养到英国的儿童谁花了他们的早年在罗马尼亚的1980年代。这些收养创造了一个强大的和道德的自然实验，允许暴露于早期逆境的影响被隔离，从而检查其对大脑发育的影响。我们正在领导英国和罗马尼亚被剥夺者研究（ERA），这是这一群体最大的发展研究，现已进入成年期。对早期全球性剥夺就业机会的影响的认识包括：（a）最初的破坏性影响;（B）调整与剥夺持续时间之间的联系;（c）对大多数人来说，明显的追赶，但对一些人来说，明显的与剥夺有关的残余问题（例如，准自闭症; ADHD）;（d）青少年发病的情绪问题;（g）社会认知和大脑过程的中介作用;（h）遗传因素对结果的调节作用。目前，在ESRC的支持下，我们正在建立丰富的纵向数据集，研究向成年早期过渡期间的心理社会适应。拟议的研究将使用成像来更深入地了解这种调整背后的神经生物学过程。我们已经在收集与这一目标相关的临床和生物学数据，并进行了成像试点研究，以提供方法的证据。我们将使用最先进的MRI设备以及结构和功能技术来检查四个逆境敏感脑网络中与剥夺相关的改变;积极/消极经验的处理;执行控制;和人际感知。我们将比较（a）罗马尼亚受试者（总N=165）;（B）英国采用的对照组（总N=52）;（c）非采用，非剥夺对照组（N=35）;（d）两组非采用/非剥夺临床（自闭症和ADHD）对照组（均N=35）的功能。功能磁共振成像分析将集中在四个实验任务所产生的激活，这些任务直接映射到四个网络：对金钱收益和损失的反应的激励延迟测试;对积极和消极社会线索的反应的情绪面部处理测试;抑制控制的停止信号测试;以及人际信息处理的移情准确性测试。T-1加权和扩散张量成像也将用于检查组间的结构差异，包括关键网络区域的体积、皮质厚度和折叠以及网络内和网络间的白色物质连接。我们将比较各组的结构和功能数据，并将我们的措施与剥夺程度和最近的纵向数据联系起来。因此，我们可以探索剥夺对行为和临床结果的影响的个体差异的神经基础;也就是说，对极端早期逆境的适应力和恢复。此外，我们将通过比较来自自闭症或ADHD临床参考对照组的神经数据与来自相应剥夺相关表型的数据，来解开剥夺和共病精神病理学的影响。最后，我们的生物样本数据库将使我们能够检查（a）遗传因素是否缓和了剥夺对大脑发育的影响，以及（B）剥夺的影响是否由控制应激反应的大脑网络的变化介导。

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.