Neuroimaging in Early Onset Depression: Longitudinal Assessment of Brain Changes

描述（由申请人提供）：该合作R 01申请的主要目的是对一个独特的学龄前发作的重度抑郁症（PO-MDD）儿童队列中腹前额叶边缘皮质网络的功能和结构的发育变化进行纵向神经影像学研究，这些网络对他们从学龄过渡到青春期早期的情绪处理至关重要。为了实现这一目标，我们建议在健康和PO-MDD儿童中的3个时间点进行结构和功能神经成像，作为正在进行的R 01的一部分，以Joan吕比，M.D.拟议研究将在该持续R 01的第5和第6（最终）年度数据收集波时采集儿童，并将在后续计划波进行额外扫描和诊断评估。详细的纵向诊断，心理社会，生物和家族史和养育数据已经在研究样本。拟议的研究提供了一个宝贵的机会，以检查抑郁症的严重程度和过程中，以及关键的生物和心理社会的调解人/主持人在儿童早期评估，对结构和功能的前额叶边缘系统的情绪系统被改变在大龄儿童和成人与抑郁症。它还将提供关于儿童MDD大脑成熟改变的第一个可用的纵向数据。初步的神经影像学数据从研究人群中获得的一部分，一个小的NIMH补充和支持几个特定的假设。为了表征基于创新的高维计算解剖学方法的区域体积和皮质完整性的差异，我们将专注于以下区域的神经形态计量学：腹内侧前额叶皮质，前膝扣带回，杏仁核和海马。扩散张量成像（DTI）也将以互补的方式用于进一步表征皮质、皮质下和白色物质束结构完整性。为了表征这些相同区域中情感处理的功能性神经解剖学差异，我们建议在情感识别范例期间使用功能性磁共振成像并评估功能性连接。基于拟定研究的设计和可用的经过充分研究的PO-MDD样本，我们将有独特的机会填补文献中的关键空白，并研究与儿童期发作MDD相关的大脑成熟的发育变化。 公共卫生相关性：拟议的研究将解决学龄前发病和儿童复发性抑郁症如何影响儿童的大脑发育。我们将探讨早期抑郁发作的慢性程度和严重程度对已知在情绪处理中起关键作用的大脑区域的结构和功能的影响。本研究将在学龄前发作MDD儿童和青春期早期进行3次扫描，并与健康对照组进行比较。基于研究的设计，我们还将有机会讨论风险和保护因素在这一过程中的作用，包括亲子关系，压力生活事件和社会支持。

DESCRIPTION (provided by applicant): The primary aim of the this collaborative R01 application is to conduct a longitudinal neuroimaging study of developmental changes in the function and structure of ventral-prefrontal limbic cortical networks key to emotion processing in a unique cohort of children with preschool onset Major Depressive Disorder (PO-MDD) as they transition from school age to early adolescence. To achieve this goal, we propose to conduct structural and functional neuroimaging at 3 timepoints in healthy and PO-MDD children ascertained as part of an ongoing R01 to Joan Luby, M.D. The proposed study would capture children at the 5th and 6th (final) annual waves of data collection in this continuing R01 and would conduct an additional scan and diagnostic assessment at a subsequent planned wave. Detailed longitudinal diagnostic, psychosocial, biological and family history and parenting data are already available in the study sample. The proposed study provides an invaluable opportunity to examine the effects of depression severity and course, as well as key biological and psychosocial mediators/moderators assessed during early childhood, on the structure and function of prefrontal limbic emotion systems known to be altered in older children and adults with MDD. It will also provide the first available longitudinal data on alterations in brain maturation in childhood MDD. Preliminary neuroimaging data from the study population have been obtained as part of a small NIMH supplement and support several of the specific hypotheses. To characterize differences in regional volume and cortical integrity based on innovative high dimensional computational anatomy approaches, we will focus on the neuromorphometry of the following regions: the ventral medial prefrontal cortex, pregenual cingulate, amygdala and hippocampus. Diffusion tensor imaging (DTI) will also be employed in a complementary fashion to further characterize cortical, subcortical and white matter tract structural integrity. To characterize differences in the functional neuroanatomy of emotion processing in these same regions, we propose to use functional magnetic resonance imaging during an emotion recognition paradigm and to assess functional connectivity. Based on the design of the proposed study and the available well-studied sample with PO-MDD, we will have the unique opportunity to fill a critical gap in the literature and investigate developmental changes in brain maturation related to childhood onset MDD. PUBLIC HEALTH RELEVANCE: The proposed study will address how preschool onset and childhood recurrent depression impact brain development in children. We will address the impact of chronicity and severity of early depressive episodes on the structure and function of brain regions known to be key in emotion processing. The study will conduct 3 scans during school age and early adolescence in children with preschool onset MDD compared to healthy controls. Based on the design of the study, we will also have the opportunity to address the role of risk and protective factors in this process including parent child relationship, stressful life events and social support.