Multimodal MR Imaging of Brain Iron in Attention Deficit Hyperactivity Disorder: A Noninvasive Biomarker That Responds to Psychostimulant Treatment?

Abstract

).q RSNA, 2014 Purpose:To comprehensively assess brain iron levels in typically developing control subjects and patients with attention deficit hyperactivity disorder (ADHD) when psychostimulant medication history is accounted for. Materials and Methods:This prospective study was approved by the institutional review board, and informed consent was obtained. Brain iron was indexed noninvasively by using magnetic resonance (MR) imaging relaxation rates (R2, R2*, R29) and magnetic field correlation (MFC) in the globus pallidus, putamen, caudate nucleus, and thalamus for 22 patients with ADHD (12 medication-naïve patients and 10 with a history of psychostimulant treatment) and 27 control subjects (age range, 8-18 years). Serum iron measures were also collected. Subgroup differences were analyzed with data-appropriate omnibus tests followed by post hoc pairwise comparisons; false discovery rate correction was conducted to control for multiple comparisons. Results:Medication-naïve ADHD patients had significantly lower striatal and thalamic MFC indexes of brain iron than did control subjects (putamen, P = .012; caudate nucleus, P = .008; thalamus, P = .012) and psychostimulant-medicated ADHD patients (putamen, P = .006; caudate nucleus, P = .010; thalamus, P = .021). Conversely, the MFC indexes in medicated patients were comparable to those in control subjects. No significant differences were detected with R2, R2*, R29, or serum measures. Conclusion:Lower MFC indexes of striatal and thalamic brain iron in medication-naïve ADHD patients and lack of differences in psychostimulant-medicated patients suggest that MFC indexes of brain iron may represent a noninvasive diagnostic biomarker that responds to psychostimulant treatment.q RSNA, 2014

Iron Status in Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis

“…The number of participants varied across studies, and ranged from 27 to 1260. Four studies were conducted in Europe [8, 13, 14, 18], one in the USA [11], one in Egypt [19], one in Brazil [20], and four in Asia [10, 21–23]. With the exception of three studies [8, 22, 23], all included studies reported medication use in the patients.…”

“…The Galbraith radial plot graph (Fig 4) showed four studies [8, 10, 11, 18] that might contribute to the high heterogeneity across studies. Further sensitivity analysis indicated that the overall pooled results did not vary substantially after omitting each of the four studies one at a time (Table 4).…”

“…Researchers have speculated that psychostimulants used in the treatment of ADHD may lead to appetite loss and reduced nutritional iron uptake, which may result in a reduction in serum ferritin in treated patients with ADHD [39]. However, the studies of Adisetiyo et al [11], Menegassi et al [20], and Calarge et al [40] revealed comparable dietary calorie and iron intake in medicated patients with ADHD and non-medicated patients with ADHD. Our subgroup meta-analysis also showed that serum ferritin levels were not lower in the treated group of patients.…”

“…Moreover, Cortese et al [8] compared brain iron levels in children with ADHD and healthy controls using magnetic resonance imaging (MRI), reporting significantly lower estimated brain iron in the bilateral thalami of children with ADHD. Similarly, Adisetiyo et al [11] found that medication-naïve patients with ADHD had lower estimated brain iron in the striatum and thalamus than did healthy controls. However, other authors have failed to find a relationship between serum ferritin and ADHD [12–14].…”

“…However, their conclusions were often inconsistent. Some authors reported that mean serum ferritin levels were lower in children with ADHD than in healthy controls [8, 10, 11]. Furthermore, Juneja et al [10] reported that serum ferritin levels were inversely correlated with ADHD symptom severity.…”