Iron Deficiency and Brain Development in Youth with Internalizing Disorders

项目摘要 抑郁和焦虑(指的是内在性)障碍在青少年中的患病率正在增加；然而， 目前还没有明确的病因。这相当令人担忧，因为这些障碍是 伴随着巨大的痛苦和损害，危及一个人迈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，近年来情况恶化 趋势。缺铁(ID)与神经精神损害有关，包括抑郁和 焦虑症状。鉴于铁在海马区树突状线粒体运动中的作用，这并不令人惊讶 神经元发育、单胺能信号和髓鞘形成。事实上，在两个独立的样本中 在医学上健康的青少年中，我们发现普遍存在的缺铁和铁储备与 内化症状的严重性。此外，我们的初步证据表明，体内的铁储备 与磁共振成像(MRI)捕捉到的大脑形态测量和连通性相关。 在这些新发现的基础上，目前的研究申请寻求在10到17年内不服药-- 有和没有内分泌障碍的老年参与者检查外周铁离子之间的关联 通过血清铁蛋白捕获的存储，以及通过定量易感地形图测量的脑铁含量 (QSM)，一种最先进的基于磁共振成像的技术(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联系，一方面，和大脑 结构、大脑连通性和白质完整性(目标2)。最后，为了建立 这一发现的临床意义，我们将检查大脑和身体铁储存和 精神症状严重程度(目标3)。 这项拟议的工作将是第一次调查ID对大脑发育和临床症状的影响 在儿童后期和青春期，这是一个发育阶段，其特征是ID和 大脑结构和功能的快速变化。最终目标是确定ID在临床上的意义。 没有贫血，通知未来的治疗干预措施。

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.