Fiani Dimitri, Kim Joo-Won, Hu Mianzhi, Salas Ramiro, Heilbronner Sarah, Powers Jacquelyn, Haque Muhammad, Dinh Stephanie, Huang Xiaofan, Worthy Darrell, Devaraj Sridevi, Xu Junqian, Calarge Chadi
Baylor College of Medicine, Houston, Texas.
Now with Cleveland Clinic Foundation, Cleveland, Ohio.
JAMA Netw Open. 2025 Jun 2;8(6):e2516687. doi: 10.1001/jamanetworkopen.2025.16687.
Although brain iron is necessary for neurogenesis, myelination, and neurotransmitter synthesis, iron deficiency (ID) is defined solely based on hematological outcomes.
To examine the association of ID without anemia with basal ganglia (BG) iron content and its structural and functional sequelae in adolescents.
DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study enrolled participants using the electronic medical record system from a large network of pediatrics clinics between December 2020 and April 2024. Otherwise healthy, unmedicated participants aged 10 to 17 years with a depressive or anxiety disorder or with no psychopathology were consecutively enrolled. Anemia and acute inflammation led to exclusion, and ID without anemia status was identified after procedure completion. Data were analyzed from May to November 2024.
Following the World Health Organization's guidelines, ID without anemia was defined as a serum ferritin concentration less than 15 ng/mL.
Participants underwent a brain magnetic resonance imaging scan to measure BG susceptibility and structures volume, a clinical interview to rate psychiatric symptoms severity, and neuropsychological testing. Multivariable regression and correlational partial least-squares analyses examined the association of ID without anemia status and BG susceptibility with each other and with BG structures volume, psychiatric symptom severity, and neuropsychological performance.
Among a total of 209 participants (122 [58%] female; mean [SD] age, 13.5 [2.2] years; 62 participants [30%] with ID without anemia), ID without anemia was associated with a significantly lower susceptibility in the caudate (Cohen d = -0.41; 95% CI, -0.72 to -0.10; P = .01) and putamen (d = -0.38; 95% CI, -0.69 to -0.07; P = .02), after accounting for age and sex. Notably, in females, the age by ID without anemia status had a significant 2-way interaction, indicating larger difference in caudate (β = 1.11; 95% CI, 0.08 to 2.15; P = .04) and putamen susceptibility (β = 0.95; 95% CI, 0.18 to 1.71; P = .02) with increasing age, favoring those without ID without anemia. None of the 2-way interactions were significant in males. Moreover, BG susceptibility was inversely associated with BG structures volume and psychiatric symptom severity and positively associated with neuropsychological performance, particularly in female adolescents.
In this cross-sectional study, ID without anemia was associated with lower striatal iron content and disrupted structure and function during adolescence, a critical period when the brain develops and accrues iron, particularly in females.
尽管脑铁对于神经发生、髓鞘形成和神经递质合成是必需的，但缺铁（ID）仅基于血液学结果来定义。
研究无贫血的缺铁与青少年基底神经节（BG）铁含量及其结构和功能后遗症之间的关联。
设计、地点和参与者：这项横断面研究于2020年12月至2024年4月期间，使用来自大型儿科诊所网络的电子病历系统招募参与者。连续招募年龄在10至17岁、患有抑郁或焦虑症或无精神病理学症状的健康、未用药参与者。贫血和急性炎症导致被排除，在程序完成后确定无贫血的缺铁状态。2024年5月至11月进行数据分析。
根据世界卫生组织的指南，无贫血的缺铁定义为血清铁蛋白浓度低于15 ng/mL。
参与者接受脑磁共振成像扫描以测量BG的磁化率和结构体积，进行临床访谈以评估精神症状严重程度，并进行神经心理学测试。多变量回归和相关偏最小二乘分析检查无贫血的缺铁状态与BG磁化率之间以及与BG结构体积、精神症状严重程度和神经心理学表现之间的关联。
在总共209名参与者中（122名[58%]为女性；平均[标准差]年龄为13.5[2.2]岁；62名[30%]有无贫血的缺铁），在考虑年龄和性别后，无贫血的缺铁与尾状核（Cohen d = -0.41；95%置信区间，-0.72至-0.10；P = 0.01）和壳核（d = -0.38；95%置信区间，-0.69至-0.07；P = 0.02）的磁化率显著降低相关。值得注意的是，在女性中，年龄与无贫血的缺铁状态存在显著的双向交互作用，表明随着年龄增长，尾状核（β = 1.11；95%置信区间，0.08至2.15；P = 0.04）和壳核磁化率（β = 0.95；95%置信区间，0.18至1.71；P = 0.02）的差异更大，有利于无无贫血的缺铁者。男性中没有双向交互作用显著。此外，BG磁化率与BG结构体积和精神症状严重程度呈负相关，与神经心理学表现呈正相关，尤其是在女性青少年中。
在这项横断面研究中，无贫血的缺铁与青少年纹状体铁含量降低以及结构和功能紊乱有关，青少年时期是大脑发育和积累铁的关键时期，尤其是在女性中。
