Multimodal MR imaging of brain iron in attention deficit hyperactivity disorder: a noninvasive biomarker that responds to psychostimulant treatment?

Abstract

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*, R2') 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*, R2', 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.

Figure 1:

Subgroup averages of MFC and R2*. A, MFC and R2* parametric maps for 27 control subjects, 10 ADHD patients with a history of psychostimulant treatment (ADHD-medicated subgroup), and 12 medication-naïve ADHD patients (ADHD-nonmedicated subgroup). Qualitative differences between control subjects and ADHD subgroups are visible only on MFC maps. B, ROIs (green) used to mask parametric maps. CN = caudate nucleus, GP = globus pallidus, PUT = putamen, THL = thalamus.

Figure 2:

Subgroup comparisons of MFC and R2* brain iron indexes. Box and whisker plots show subgroup variations in indexes (medians, 25th and 75th percentiles, minimum, maximum, outliers). CN = caudate nucleus, GP = globus pallidus, PUT = putamen, THL = thalamus. A, Subgroup comparisons of MFC in globus pallidus, putamen, caudate nucleus, and thalamus show a significant reduction in mean striatal (putamen and caudate nucleus) and median thalamic MFC in ADHD-nonmedicated subgroup compared with control group and ADHD-medicated subgroup. No significant differences in MFC were found between control group and ADHD-medicated subgroup. B, Subgroup comparisons of R2* indexes in all regions did not show any significant differences in means. * = P < .05, ** = P < .01, *** = P < .005 (all FDR corrected).