Iron Deficiency and Brain Development in Youth with Internalizing Disorders

项目摘要 抑郁症和焦虑症（指内化）在青少年中的患病率正在增加;然而， 没有明确的病因。这是非常令人担忧的，因为这些疾病是 伴随着巨大的痛苦和损伤，危及一个人走向富有成效的成年的轨迹， 并增加自杀风险;后者是青少年死亡的第二大原因，最近恶化 趋势铁缺乏症（ID）与神经精神损害有关，包括抑郁和 焦虑症状这并不奇怪，因为铁在海马神经元树突线粒体运动中的作用。 神经元发育、单胺能信号传导和髓鞘形成。事实上，在两个独立的样本中， 在医学健康的青少年中，我们发现普遍的ID和铁储存之间的负相关， 内化症状的严重程度此外，我们的初步证据表明，身体铁储存是 与脑形态测量和连接相关，如通过磁共振成像（MRI）捕获的。 在这些新发现的基础上，目前的研究申请旨在招募未用药的10至17岁儿童， 有和没有内化障碍的老年参与者，以检查外周铁 储存，如血清铁蛋白所捕获，和脑铁含量，如定量易感性绘图所测量 (QSM)，一种最先进的基于MRI的技术（目标1）。此外，为了确定ID对大脑的影响， 发展，我们将研究大脑和身体铁储存之间的关联，一方面， 另一方面是结构、大脑连接和白色物质完整性（目标2）。最后，为了建立 研究结果的临床意义，我们将研究大脑和身体铁储存之间的联系， 精神症状严重程度（目标3）。 这项拟议中的工作将首次调查ID对大脑发育和临床症状的影响 在儿童后期和青春期，这是一个以ID风险增加为特征的发育期， 快速的大脑结构和功能变化。最终目标是确定ID的临床意义， 没有贫血，为未来的治疗干预提供信息。

Project Summary Depressive and anxiety (referred to internalizing) disorders are increasing in prevalence in adolescents; yet, no specific etiology has been clearly demonstrated. This is quite concerning given that these disorders are associated with substantial distress and impairment, jeopardize one's trajectory towards a productive adulthood, and increase suicide risk; the latter being the 2nd leading cause of death in adolescents, with worsening recent trends. Iron deficiency (ID) has been associated with neuropsychiatric impairment, including depressive and anxiety symptoms. This is not surprising, given iron's role in dendritic mitochondrial motility during hippocampal neuron development, monoaminergic signaling, and myelination. In fact, across two independent samples of medically-healthy adolescents, we have found prevalent ID and an inverse association between iron stores and the severity of internalizing symptoms. Moreover, our preliminary evidence suggests that body iron stores are associated with brain morphometry and connectivity, as captured by magnetic resonance imaging (MRI). Building on these novel findings, the current research application seeks to enroll unmedicated 10 to 17 year- old participants with and without internalizing disorders to examine the association between peripheral iron stores, as captured by serum ferritin, and brain iron content, as measured by quantitative susceptibility mapping (QSM), a state-of-the-art MRI-based technique (Aim 1). Moreover, in order to establish the impact of ID on brain development, we will examine the association between brain and body iron stores, on the one hand, and brain structure, brain connectivity, and white matter integrity, on the other (Aim 2). Finally, in order to establish the clinical significance of the findings, we will examine the association between brain and body iron stores and psychiatric symptom severity (Aim 3). The proposed work will be the first to investigate the effect of ID on brain development and clinical symptoms in late childhood and adolescence, a developmental period characterized by increased risk for ID as well as rapid brain structural and functional changes. The ultimate goal is to determine the clinical significance of ID, in the absence of anemia, informing future therapeutic interventions.