Neuroimaging in Early Onset Depression: Longitudinal Assessment of Brain Changes

描述（由申请人提供）：本R01合作申请的主要目的是开展纵向神经影像学研究，研究学龄前重度抑郁症（PO-MDD）儿童从学龄过渡到青春期早期情绪处理的关键腹侧-前额叶皮层网络的功能和结构的发育变化。为了实现这一目标，我们建议在健康和PO-MDD儿童的3个时间点进行结构和功能神经成像，这些儿童被确定为Joan Luby医学博士正在进行的R01的一部分。拟议的研究将在这个持续的R01的第5和第6（最终）年度数据收集波中捕获儿童，并将在随后的计划波中进行额外的扫描和诊断评估。研究样本中已有详细的纵向诊断、心理社会、生物学和家族史以及养育子女的数据。提出的研究提供了一个宝贵的机会来检查抑郁症的严重程度和病程的影响，以及在儿童早期评估的关键生物和社会心理介质/调节因子，对已知在老年儿童和重度抑郁症成人中发生改变的前额叶边缘情绪系统的结构和功能。它还将提供关于儿童重度抑郁症中大脑成熟变化的第一个可用的纵向数据。从研究人群中获得的初步神经影像学数据作为NIMH小补充的一部分，支持了几个特定的假设。为了基于创新的高维计算解剖学方法表征区域体积和皮层完整性的差异，我们将重点研究以下区域的神经形态测量学：腹侧内侧前额叶皮层、前扣带、杏仁核和海马。弥散张量成像（DTI）也将以一种互补的方式进一步表征皮层、皮层下和白质束的结构完整性。为了描述这些相同区域情绪处理的功能神经解剖学差异，我们建议在情绪识别范式中使用功能磁共振成像并评估功能连通性。基于本研究的设计和现有的对PO-MDD的充分研究样本，我们将有独特的机会填补文献中的一个关键空白，研究与儿童期发病MDD相关的脑成熟发育变化。

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.