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：
10478058
负责人：
Chadi A. Calarge
金额：
$ 63.72万
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/10478058
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.

项目摘要青少年患病率的抑郁和焦虑症（称为内部化）疾病正在增加。然而，没有明确证明具体的病因。考虑到这些疾病是与实质性的困扰和障碍相关，危害一个人对成年的轨迹，并增加自杀风险；后者是青少年死亡的第二大死亡原因，最近恶化趋势。铁缺乏症（ID）与神经精神障碍有关，包括抑郁和焦虑症状。鉴于铁在海马期间的树突状线粒体运动中的作用，这并不奇怪神经元发育，单胺能信号和髓鞘形成。实际上，在两个独立样本中医学健康的青少年，我们发现了ID普遍存在的ID和铁存储之间的逆关联内部症状的严重性。此外，我们的初步证据表明，人体铁储存是与磁共振成像（MRI）捕获的脑形态计量学和连通性相关。在这些新颖的发现的基础上，当前的研究申请旨在注册未对10至17年的未经测验患有或没有内在疾病的老参与者检查周围铁之间的关联由血清铁蛋白和脑铁含量捕获的商店，如定量敏感性映射测量（QSM），一种基于最先进的MRI技术（AIM 1）。此外，为了建立ID对大脑的影响开发，我们将一方面检查大脑和人体铁储存之间的关联，而大脑另一方面的结构，大脑连通性和白质完整性（AIM 2）。最后，为了建立调查结果的临床意义，我们将检查大脑和人体铁储存之间的关联以及精神病症状严重程度（AIM 3）。拟议的工作将是第一个研究ID对大脑发育和临床症状的影响的工作在儿童时期和青春期，以ID风险增加以及大脑结构和功能变化迅速。最终目标是确定ID的临床意义缺乏贫血，告知未来的治疗干预措施。