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

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. 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. 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. 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.