Neuromelanin magnetic resonance imaging reveals increased dopaminergic neuron activity in the substantia nigra of patients with schizophrenia

PLoS One. 2014 Aug 11;9(8):e104619. doi: 10.1371/journal.pone.0104619. eCollection 2014.

Abstract

Purpose: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenergic Neurons / pathology
  • Adult
  • Aged
  • Case-Control Studies
  • Dopaminergic Neurons / pathology*
  • Female
  • Humans
  • Magnetic Resonance Imaging*
  • Male
  • Melanins*
  • Middle Aged
  • Schizophrenia / pathology*
  • Substantia Nigra / pathology*

Substances

  • Melanins
  • neuromelanin

Grants and funding

This work was supported by research grants from KAKENHI, 22390225-Grant-in-Aid for Scientific Research (B), 23659565-Grant-in-Aid for Challenging Exploratory Research and Grant-in-Aid for Scientific Research on Innovative Areas (Comprehensive Brain Science Network) from the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT), and the Japan Foundation for Neuroscience and Mental Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.