Emerging research implicates iron deficiency in childhood externalizing disorders featuring deficits in attention and cognitive control, such as Attention-Deficit/Hyperactivity Disorder (ADHD) and Oppositional Defiant Disorder. In children, iron deficiency is hypothesized to contribute to these deficits as a result of iron?s critical role in the synthesis and expression of important neurotransmitters such as dopamine and norepinephrine, in the functioning of the striatum, and in myelination of the frontal lobe, all of which have been linked to impairment in attention and cognitive control in ADHD. Previous research has largely utilized peripheral (blood-based) iron measures in evaluating these associations; however, peripheral iron measures may not accurately represent iron concentrations in the brain. Recent developments in neuroimaging methodologies now allow for non-invasive, ultra-high resolution maps of tissue magnetic susceptibility differences, which correlate strongly with tissue iron concentrations in gray matter. Only two studies to date have assessed the relationship between brain iron concentrations and disorders of attention and cognitive control in children via neuroimaging, with both providing preliminary evidence of reduced brain iron among school-aged children with ADHD symptomatology. The goal of the proposed project is to better understand the early developmental course of brain iron concentration in (human) children and its relationship to critical cognitive systems implicated in externalizing behavior problems. To accomplish this goal, we will recruit 40 children between the ages of 6 and 8 years, half of whom have a history of iron deficiency (measured peripherally) in infancy and half of whom do not. Participants will complete: 1) a high resolution neuroimaging study at 7 Tesla to estimate concurrent brain iron concentrations; 2) a blood draw to assess concurrent peripheral iron concentrations; and 3) a focused neuropsychological assessment to evaluate concurrent attention and cognitive control, as well as other cognitive systems (e.g., language and visual perception) which are hypothesized to be less impacted by early iron deficiency. In addition, participants? parents and teachers will be asked to complete ratings of behaviors associated with deficits in attention and cognitive control. This study represents the first use of anatomic imaging techniques to evaluate brain iron concentrations in young children, in association with early peripheral iron indices, to determine the relation between iron status and critical cognitive systems.
The public health relevance of this project is underscored by the prevalence and long-term implications of childhood deficits in attention and cognitive control, which represent a significant risk factor for negative educational, social, occupational, and criminal outcomes, as well as a considerable cost to society in terms of lost productivity, medical costs associated with accidents, injuries, and prescription medication, and costs associated with special education services. As such, accurate identification of etiological mechanisms contributing to deficits in attention and cognitive control is essential to the development of appropriate prevention and treatment efforts. The proposed study will offer preliminary data to further clarify the value of population-based prevention efforts to ensure early iron sufficiency, which will inform longitudinal studies designed to assess the developmental timing and malleability of brain-based iron deficiency during childhood.
