title: Neuromelanin magnetic resonance imaging reveals increased dopaminergic neuron activity in the substantia nigra of patients with schizophrenia.
abstract: OBJECTIVE
  The dopamine hypothesis suggests that excessive dopamine release results in the symptoms of schizophrenia. The purpose of this study was to elucidate the dopaminergic and noradrenergic neurons using 3-T neuromelanin magnetic resonance imaging (MRI) in patients with schizophrenia and healthy control subjects.
  
  
  METHODS
  We prospectively examined 52 patients with schizophrenia (M: F = 27∶25, mean age, 35 years) and age- and sex-matched healthy controls. Using a 3T MRI unit, we obtained oblique T1-weighted axial images perpendicular to the brainstem. We measured the signal intensity and area for the substantia nigra (SNc), midbrain tegmentum, locus ceruleus (LC), and pons. We then calculated the contrast ratios (CR) for the SNc (CRSN) and LC (CRLC), which were compared between patients and healthy controls using unpaired t-tests.
  
  
  RESULTS
  The SNc and LC were readily identified in both patients and healthy controls as areas with high signal intensities in the posterior part of the cerebral peduncle and in the upper pontine tegmentum. The CRSN values in patients were significantly higher than those in healthy controls (10.89±2.37 vs. 9.6±2.36, p<0.01). We observed no difference in the CRLC values between the patients and healthy controls (14.21±3.5 vs. 13.44±3.37, p = 0.25). Furthermore, there was no difference in area of the SNc and LC between schizophrenia patients and controls.
  
  
  CONCLUSIONS
  Neuromelanin MRI might reveal increased signal intensity in the SNc of patients with schizophrenia. Our results indicate the presence of excessive dopamine products in the SNc of these patients.
authors.affiliation: Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Tsukabe
authors.affiliation: Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kunitomi
authors.affiliation: Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Nishizawa
authors.affiliation: Research Center for Children's Mental Development, United Graduate School of Child Development, Osaka University, Suita, Japan; Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Hashimoto
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Hidenaga
authors.initials: H
authors.lastname: Yamamori
authors.affiliation: Department of Psychiatry, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Fujimoto
authors.affiliation: Departments of Biofunctional Imaging and Immunology, Frontier Research Center, Osaka University, Suita, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Fukunaga
authors.affiliation: Diagnostic and Interventional Radiology, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Tomiyama
mesh_terms: D000293:Adolescent; D059331:Adrenergic Neurons / Q000473:pathology; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D059290:Dopaminergic Neurons / Q000473:pathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008543:Melanins; D008875:Middle Aged; D012559:Schizophrenia / Q000473:pathology*; D013378:Substantia Nigra / Q000473:pathology*
chemical_list: D008543:Melanins; C014121:neuromelanin
references.citation: Neuroradiology. 2010 Feb;52(2):83-9
references.pmid: 19756561
references.citation: Science. 1986 Dec 19;234(4783):1558-63
references.pmid: 2878495
references.citation: J Clin Exp Neuropsychol. 2006 Feb;28(2):270-82
references.pmid: 16484098
references.citation: Magn Reson Med Sci. 2006 Dec;5(4):197-200
references.pmid: 17332710
references.citation: Biol Psychiatry. 2008 Sep 1;64(5):401-6
references.pmid: 18452894
references.citation: Rinsho Shinkeigaku. 2011 Jan;51(1):14-20
references.pmid: 21387694
references.citation: Neuroradiology. 2013 Jun;55(6):719-24
references.pmid: 23525598
references.citation: Schizophr Bull. 1987;13(2):261-76
references.pmid: 3616518
references.citation: Mov Disord. 2012 Jun;27(7):822-30
references.pmid: 22649063
references.citation: Am J Psychiatry. 2008 May;165(5):579-87
references.pmid: 18413704
references.citation: Brain. 2013 Nov;136(Pt 11):3242-51
references.pmid: 24097339
references.citation: Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):8104-9
references.pmid: 10884434
references.citation: Biol Psychiatry. 2005 Mar 15;57(6):688-91
references.pmid: 15780858
references.citation: Schizophr Bull. 2010 May;36(3):472-85
references.pmid: 20453041
references.citation: Psychiatry Clin Neurosci. 2006 Jun;60(3):332-9
references.pmid: 16732750
references.citation: J Clin Neurosci. 2011 Aug;18(8):1093-6
references.pmid: 21719292
references.citation: Neurosci Lett. 2013 Apr 29;541:93-8
references.pmid: 23428505
references.citation: Clin Schizophr Relat Psychoses. 2010 Apr;4(1):56-73
references.pmid: 20643630
references.citation: Brain. 1974 Sep;97(3):489-98
references.pmid: 4423478
references.citation: Int J Psychiatry Clin Pract. 2013 Feb;17(1):10-5
references.pmid: 22335467
references.citation: Neuroreport. 2008 Nov 19;19(17):1649-54
references.pmid: 18852680
references.citation: J Neural Transm (Vienna). 2006 Jun;113(6):757-67
references.pmid: 16755380
references.citation: Eur Neurol. 2013;70(1-2):70-7
references.pmid: 23796701
references.citation: Lancet. 1995 Oct 28;346(8983):1130-1
references.pmid: 7475604
references.citation: Neuroreport. 2006 Jul 31;17(11):1215-8
references.pmid: 16837857
references.citation: Drugs Aging. 2008;25(8):665-82
references.pmid: 18665659
references.citation: Mov Disord. 2011 Aug 1;26(9):1633-8
references.pmid: 21491489
references.citation: Psychiatry Clin Neurosci. 2014 Jul;68(7):534-41
references.pmid: 24447376
references.citation: Aust N Z J Psychiatry. 2012 Dec;46(12):1120-35
references.pmid: 22833579