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

• 批准号: 10099487
• 负责人: Chadi A. Calarge
• 金额: $ 72.01万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 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/10099487
• 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; Preventive Intervention; 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; psychiatric symptom; reward processing; suicidal risk; trend; white matter

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，我们发现了普遍存​​在的 ID 以及铁储存和铁储存之间的负相关关系。 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 有或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，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。