Iron Deficiency and Brain Development in Youth with Internalizing Disorders

患有内化障碍的青少年缺铁和大脑发育

基本信息

批准号：
10265539
负责人：
Chadi A. Calarge
金额：
$ 64.07万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-17 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10265539
关键词：
17 year old Adolescence Adolescent Adult Anatomy Anemia Animals Anisotropy Anxiety Area Basal Ganglia Blood Bone Marrow Brain Cause of Death Child Childhood Clinical Cognition Cognitive deficits Corpus striatum structure Cross-Sectional Studies Data Development Diagnosis Diffusion Magnetic Resonance Imaging Disease Distress Enrollment Enzymes Erythrocytes Etiology Female Female Adolescents Female of child bearing age Ferritin Functional Magnetic Resonance Imaging Future Goals Growth Guidelines Hippocampus (Brain)Impairment Iron Laboratories Link MRI Scans Magnetic Resonance Imaging Measures Medical Menstruation Mental Depression Metabolism Mitochondria Neurotransmitters Organ Oxygen Participant Peripheral Play Predisposition Prevalence Production Research Rest Risk Role Sampling Serum Severities Signal Transduction Structure Sum Symptoms Techniques Therapeutic Intervention Tissues Work Youth age group anxiety symptoms base cell motility child depression clinically significant cofactor cognitive process depressive symptoms emotion regulation human data iron deficiency male micronutrient deficiency morphometry myelination neural circuit neuron development neuropsychiatry novel pre-clinical preventive intervention psychiatric symptom reward processing suicidal risk trend white matter

项目摘要

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.

项目概要抑郁和焦虑（称为内化）障碍在青少年中的患病率正在增加；然而，尚未明确证明具体病因。鉴于这些疾病是与严重的痛苦和损伤相关，危及一个人迈向富有成效的成年期的轨迹，并增加自杀风险；后者是青少年死亡的第二大原因，并且最近恶化趋势。缺铁 (ID) 与神经精神障碍有关，包括抑郁症和抑郁症焦虑症状。鉴于铁在海马期间树突状线粒体运动中的作用，这并不奇怪神经元发育、单胺能信号传导和髓鞘形成。事实上，在两个独立样本中在身体健康的青少年中，我们发现 ID 普遍存在，并且铁储存和铁储存之间存在负相关关系。内化症状的严重程度。此外，我们的初步证据表明，体内铁储备与磁共振成像（MRI）捕获的大脑形态测量和连接性相关。基于这些新颖的发现，当前的研究申请旨在招募未接受药物治疗的 10 至 17 岁儿童有和没有内化障碍的老年参与者检查外周铁之间的关联通过血清铁蛋白捕获的储存量和通过定量磁敏图测量的脑铁含量 (QSM)，一种最先进的基于 MRI 的技术（目标 1）。此外，为了确定 ID 对大脑的影响发展过程中，我们一方面将研究大脑和身体铁储存之间的关联，另一方面，另一方面，其结构、大脑连接性和白质完整性（目标 2）。最后，为了建立研究结果的临床意义，我们将检查大脑和身体铁储存之间的关联精神症状的严重程度（目标 3）。拟议的工作将是第一个研究智力障碍对大脑发育和临床症状的影响的研究在儿童晚期和青春期，这是一个以智力障碍和智力障碍风险增加为特征的发育时期大脑结构和功能的快速变化。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。