权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Brain iron as a neurodevelopmental mechanism for transdianostic executive dysfunction

脑铁作为跨神经执行功能障碍的神经发育机制

基本信息

批准号：
10590726
负责人：
Bart Larsen
金额：
$ 5.84万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-01 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10590726
关键词：
Adolescence Adolescent Affect Age Age Months Attention deficit hyperactivity disorder Automobile Driving Award Basal Ganglia Biometry Blood Blood Tests Brain Brain Mapping Characteristics Child Childhood Clinical Cognitive Communities Corpus striatum structure Data Data Set Development Diagnostic Executive Dysfunction Female Foundations Functional Magnetic Resonance Imaging Goals Gur Hemoglobin Image Individual Individual Differences Intervention Iron Laboratories Life Link MRI Scans Magnetic Resonance Imaging Maps Mediating Medical Records Mental disorders Mentorship Modeling Nutrient Outcome Pathologic Pathway interactions Pennsylvania Peripheral Phase Philadelphia Physiology Predisposition Prevalence Psychoses Puberty Public Health Recording of previous events Research Resolution Sampling Severity of illness Sex Differences Short-Term Memory Societies Source Symptoms T2 weighted imaging Testing Time Training University resources Work Youth age related aged brain abnormalities clinically relevant cognitive process cognitive testing cohort data resource early adolescence early childhood executive function improved improved outcome iron deficiency male neurobiological mechanism neuroimaging neuropsychiatry neurotransmission programs prospective recruit response routine screening screening screening guidelines statistics translational model

项目摘要

PROJECT ABSTRACT Executive function is a multifaceted construct that includes higher-order cognitive processes such as response inhibition, working memory, and goal selection. Executive abilities improve throughout adolescence, and deficits of executive function, or executive dysfunction, are a transdiagnostic feature of many psychiatric disorders that emerge during this period of development. Understanding the underlying neurodevelopmental mechanisms that contribute to executive dysfunction is a critical prerequisite for targeted interventions. Iron deficiency is the most common nutrient deficiency in the world and is a known source of executive dysfunction during the vulnerable windows of early childhood and adolescence. However, despite its prevalence and impact, the underlying neurobiological mechanisms are not fully understood. This proposal focuses on a potentially critical but under-explored mechanism linking iron deficiency to transdiagnostic executive dysfunction: brain iron deficiency. Aim 1 will define how brain iron deficiency during adolescence mediates the effect of peripheral iron deficiency on executive dysfunction. We will first investigate this relationship in a large community-based sample (n=9,500 with peripheral iron and cognitive assessment, n=1,601 with neuroimaging) and then replicate and extend the model to a sample that is enriched for individuals with psychiatric disorders. Aim 2 will use a prospectively collected sample of adolescents with and without a history of iron deficiency in routine screenings at 9-18monts of age to determine how iron deficiency across childhood and adolescence impacts brain iron deficiency and executive dysfunction in adolescence. Critically, this aim will inform a multi-hit model whereby iron deficiency across childhood and adolescence will be associated with greater brain iron deficiency and thus more severe executive function than having iron deficiency in only one of the two time periods. Finally, Aim 3 will examine how sex differences in peripheral iron deficiency impact sex differences in brain iron after the onset of puberty. Together, these aims will identify both the timing of vulnerability and the neurobiological mechanisms underlying executive dysfunction, thus informing translational models for targeted treatments and interventions. The support of this K99/R00 Pathway to Independence award will provide the applicant with the training necessary to achieve these aims, including training in developmental neuropsychiatry, cognitive assessment, quantitative magnetic resonance imaging, and advanced biostatistics. These training objectives will be accomplished with the support of an outstanding mentorship team, Drs. Satterthwaite, Gur, Witschey, Shinohara, Wehrli, and Georgieff, and the world class technical and intellectual resources of the University of Pennsylvania. Together, the proposed scientific aims and training objectives will form the foundation for an independent research program aimed at uncovering the neurodevelopmental mechanisms for executive dysfunction in youth with mental illness.