Deprivation and Threat: Dimensions of Early Experience and Neural Development

 描述(由申请者提供)：广泛的研究发现心理健康和童年逆境(CA)之间存在强有力的联系，包括从虐待儿童到贫困的各种暴露。尽管这些发现的力度和一致性很强，但产生这种联系的机制仍然没有得到很好的说明。特别是，过去的研究未能确定具体的环境经历如何影响特定的神经过程。这些局限性源于难以精确量化儿童相关的CA和神经变量。目前的建议通过利用NIH资助的独特的、特征良好的纵向队列儿童来解决这些限制，在这些队列中，CA的多个方面得到了准确的评估，并使用严格的神经成像方法来量化特定神经回路中的功能。我们将使用这些方法来测试一个新的概念性框架，该框架描述了特定类型的环境经验如何影响特定的神经过程，以满足NIMH战略计划的目标1。我们的模型认为，不同类型的CA对神经发育有不同的影响。我们所做的主要区分是创伤和剥夺。创伤暴露包括伤害或伤害威胁，导致通过边缘通路调节恐惧学习，这些通路在动物身上很有特点，并在物种之间保存。我们认为，儿童创伤改变了负价系统中支持情绪学习的回路的发展，包括杏仁核和腹内侧额前皮质(PFC)。相比之下，剥夺包括缺乏预期的认知和社会投入以及环境的复杂性。动物研究表明，剥夺通过劫持典型的突触修剪过程来扰乱PFC和顶叶皮质的发育。因此，我们预测，社会认知剥夺会影响认知控制系统，导致特定年龄的前额叶背外侧皮质和顶上皮质厚度和体积的减少，并降低这些区域支持的认知控制任务的绩效。显然，创伤和剥夺是相关的。我们独特的设计将通过丰富的初步数据在不同的维度上衡量这些体验，这些数据表明创伤和剥夺对神经发育的不同影响，即使在高暴露共存的样本中也是如此。我们提出的概念模型将通过获取300名儿童(1/3贫困儿童、1/3接近贫困儿童和1/3中产阶级儿童)的现有样本的结构和功能MRI数据进行测试，这些儿童的CA暴露具有显著的变异性。在这项研究的前几波中已经测量了精神病理学，并将在研究期间多次收集。研究结果将提供关于环境经验的特定维度如何影响特定神经过程的关键信息。阐明这些机制不仅将建立关于不利环境如何以增加精神病理风险的方式改变神经发育的知识，还将为旨在降低暴露在创伤和剥夺中的儿童的精神病理风险的预防性干预提供可能的目标。

 DESCRIPTION (provided by applicant): Extensive research finds robust links between mental health and childhood adversity (CA), encompassing diverse exposures from child abuse to poverty. Despite the strength and consistency of these findings, the mechanisms producing such links remain poorly specified. In particular, past research has failed to identify how specifi environmental experiences influence specific neural processes. Such limitations arise from the difficulty of precisely quantifying relevant CA and neural variables in children. The current proposal addresses these limitations by capitalizing on a unique, well characterized NIH-funded longitudinal cohort of children where multiple aspects of CA have been precisely assessed and use of rigorous neuroimaging methods to quantify functioning in specific neural circuits. We will use these methods to test a novel conceptual framework delineating how specific types of environmental experience influence specific neural processes, addressing Objective 1 of the NIMH Strategic Plan. Our model argues that different types of CA have distinct effects on neural development. The central distinction we make is between trauma and deprivation. Trauma exposure involves harm or threat of harm, resulting in fear learning mediated by limbic pathways that are well characterized in animals and conserved across species. We argue that child trauma alters development of circuits in the Negative Valence System that support emotional learning encompassing amygdala and ventromedial prefrontal cortex (PFC). In contrast, deprivation involves absence of expected cognitive and social inputs and environmental complexity. Animal research shows that deprivation disrupts development in PFC and parietal cortex by hijacking the typical process of synaptic pruning. Thus we predict that social-cognitive deprivation influences Cognitive Control Systems, resulting in age-specific reductions in thickness and volume of dorsolateral PFC and superior parietal cortex and reduced performance on cognitive control tasks supported by these areas. Clearly, trauma and deprivation are correlated. Our unique design will measure these experiences on separate dimensions informed by rich preliminary data indicating distinct effects of trauma and deprivation on neural development even in samples with high exposure co-occurrence. Our proposed conceptual model will be tested by acquiring structural and functional MRI data on an existing sample of 300 children (1/3 in poverty, 1/3 near poverty, and 1/3 middle class) followed since early childhood with significant variability in CA exposure. Psychopathology has been measured in previous waves of the study and will be collected multiple times during the study period. Study findings will provide critical information about how specific dimensions of environmental experience influence specific neural processes. Elucidating these mechanisms will not only build knowledge of how adverse environments alter neural development in ways that increase risk for psychopathology, but will also suggest possible targets for preventive interventions aimed at reducing psychopathology risk in children exposed to trauma and deprivation.