title: Multimodal MR imaging of brain iron in attention deficit hyperactivity disorder: a noninvasive biomarker that responds to psychostimulant treatment?
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: From the Center for Biomedical Imaging (V.A., J.H.J., A.T., R.L.D., J.A.H.), Department of Radiology and Radiological Science (V.A., J.H.J., A.T., R.L.D., J.A.H.), Department of Psychiatry and Behavioral Sciences (K.M.G.), and Department of Neurosciences (J.A.H.), Medical University of South Carolina, 68 President St, Bioengineering Building, 2nd Floor, Charleston, SC 29425; Center for Biomedical Imaging, Department of Radiology (E.F., F.X.C.), Child Study Center, Department of Child and Adolescent Psychiatry (A.D.M., F.X.C.), and Department of Physiology and Neuroscience (F.X.C.), New York University School of Medicine, New York, NY; and Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY (F.X.C.).
authors.forename: Vitria
authors.initials: V
authors.lastname: Adisetiyo
authors.forename: Jens H
authors.initials: JH
authors.lastname: Jensen
authors.forename: Ali
authors.initials: A
authors.lastname: Tabesh
authors.forename: Rachael L
authors.initials: RL
authors.lastname: Deardorff
authors.forename: Els
authors.initials: E
authors.lastname: Fieremans
authors.forename: Adriana
authors.initials: A
authors.lastname: Di Martino
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Gray
authors.forename: Francisco X
authors.initials: FX
authors.lastname: Castellanos
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Helpern
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001931:Brain Mapping / Q000379:methods; D016022:Case-Control Studies; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D002648:Child; D017352:Echo-Planar Imaging; D005260:Female; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D064847:Multimodal Imaging; D011446:Prospective Studies
chemical_list: D015415:Biomarkers; D000697:Central Nervous System Stimulants; D007501:Iron