The regional distribution of brain iron and its relation to behaviors in children and adolescents

354 

Abstract Submission 

Bryan Yoon¹, Lanxin Ji², Amyn Majbri³, Ellyn Kennelly⁴, Tanya Bhatia³, Mark Duffy², Alexis Taylor⁴, Moriah Thomason⁵

¹New York University, New York, NY, ²NYU Langone Health, New York, NY, ³New York University Medical Center, New York, NY, ⁴Wayne State University, Detroit, MI, ⁵NYU Langone Medical Center, New York, NY

Bryan Yoon, MD, PhD  
New York University
New York, NY

Lanxin Ji  
NYU Langone Health
New York, NY

Amyn Majbri  
New York University Medical Center
New York, NY

Ellyn Kennelly  
Wayne State University
Detroit, MI

Tanya Bhatia  
New York University Medical Center
New York, NY

Mark Duffy, MS  
NYU Langone Health
New York, NY

Alexis Taylor  
Wayne State University
Detroit, MI

Moriah Thomason  
NYU Langone Medical Center
New York, NY

Brain iron plays an essential role in human brain development by influencing neurotransmitter function, supporting myelin formation and DNA synthesis (Rouault, 2013; Ward et al., 2014) and modulating metabolic energy production (Larsen & Luna, 2015). Preadolescence represents a critical period during which non-heme iron rapidly accumulates to meet the demands of brain maturation (Treit et al., 2021). Recent studies have started to reveal close associations between adolescent basal ganglia brain iron and cognitive function (Darki et al., 2016; Hect et al., 2018), and have shown that psychiatric disorders are more prevalent in youth with iron deficiency (Cortese et al., 2011), autism (Tang et al., 2021), and first-episode psychosis (Xu et al., 2021). However, to date, no studies have addressed brain iron in the context of early adolescent brain development and its impact on internalizing, externalizing, and attention behaviors in a well-characterized, low-income, predominantly minority early adolescent sample. Assessing such behavior is particularly important as it allows for the detection of prodromal symptoms in advance, leading to early intervention and a better prognosis. We will test the hypothesis that decreased non-heme iron, indicative of delayed neurological development, will be associated with elevated behaviors in both internalizing and externalizing domains. Furthermore, we expect specificity in which brain structures reflect different iron levels across internalizing, externalizing, and attention domains.

Imaging data were acquired from 51 adolescents and children (34 females), aged 7 to 16 (M = 12.15, SD = 2.40), who were enrolled in the ongoing Perinatal Imaging of Neural Connectivity (PINC) study. This study initially conducted fetal MRI studies in pregnant women and now follows the developmental progress of these children. Non-heme iron levels in the substructures of basal ganglia and hippocampus were measured using susceptibility-weighted imaging on a Siemens Verio 3 T scanner equipped with a 12-channel head coil. The iron content in substructures of the basal ganglia and hippocampus was estimated in vivo from an 11-echo multiple gradient-echo sequence with a voxel size of 0.5 × 0.5 × 2 mm, echo times (TE) = 5.68–31.38 ms with an inter-echo interval of 2.57 ms, repetition time = 37 ms, flip angle = 15°, bandwidth = 465 Hz/pixel, and field of view = 512 × 384. Internalizing (anxiety, depressive, and somatic symptoms), externalizing (disruptive conduct, impulsive, and addictive symptoms), and attention behaviors of children and adolescents were assessed using the Child Behavior Checklist (CBCL) (Achenbach, 1994).

Lower brain iron in both the substantia nigra (Fig. 1a) and hippocampus (Fig. 1b) was correlated with poorer attention levels, as shown in Fig. 2a and Fig. 2b. Conversely, the higher brain iron content of the left red nucleus (Fig. 1c) was correlated with severe internalizing behavior, as shown in Fig. 2c.

In this study, we present results on how different regional brain iron contents are associated with the behaviors of adolescents and children. While replicating previous studies that reported a correlation between lower brain regional iron contents and the decline in attention levels (Cortese et al., 2011), our results mark the first study to demonstrate a correlation between internalizing behavior and higher iron levels in the red nucleus. We speculate that this pattern indicates an overdevelopment of the red nucleus, responsible for managing the shift from one motor response to another. Our hypothesis is that individuals more vulnerable to anxiety, depressive, and somatic symptoms tend to undergo a process of overdeveloping the red nucleus as a compensatory mechanism. Our future work will explore whether overdevelopment is associated with heightened rumination, and whether youth with using different coping strategies show varied brain iron loading.

Neurodevelopmental/ Early Life (eg. ADHD, autism) ¹

Early life, Adolescence, Aging ²

Other Methods

Attention Deficit Disorder

Basal Ganglia

MRI

NORMAL HUMAN

PEDIATRIC