Neuromelanin Magnetic Resonance Imaging Reveals Increased Dopaminergic Neuron Activity in the Substantia Nigra of Patients with Schizophrenia

Abstract

PurposeThe 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.MethodsWe 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.ResultsThe 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.ConclusionsNeuromelanin 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.

Life span pigmentation changes of the substantia nigra detected by neuromelanin‐sensitive MRI

“…First, conventional sagittal T1 images were obtained for setting up the scanning field. The 30‐dimnesional spoiled gradient recalled neuromelanin‐sensitive T1‐weighted images with magnetization transfer were acquired with the following parameters that were optimized on the basis of a previous protocol: TR, 38.4 milliseconds; TE, 3 milliseconds; flip angle, 20; slice thickness, 2 mm; Field of view (FOV), 19.2; matrix: 480 × 192; scanning time, 3.25 minutes. Thirty axial image slices were obtained on each individual with parallel alignment to the anterior callosum‐posterior callosum line.…”

Protein Markers of Neurotransmitter Synthesis and Release in Postmortem Schizophrenia Substantia Nigra

“…Some postmortem studies indicate increased dopamine activity, protein, and mRNA levels (Howes et al, 2013;Mueller et al, 2004;Toru et al, 1988), whereas others do not (Perez-Costas et al, 2012;Ichinose et al, 1994). Imaging studies report disturbed functional connectivity (Hadley et al, 2014) that is correlated with increased dopamine synthesis capacity (Howes et al, 2013;Watanabe et al, 2014) and symptom severity (Yoon et al, 2014).…”

Subcomponents of brain T2* relaxation in schizophrenia, bipolar disorder and siblings: A Gradient Echo Plural Contrast Imaging (GEPCI) study

“…Including additional brain regions, such as the midbrain or cerebellum, will provide further information about pathologic processes that may be involved in psychiatric disorders. For example, midbrain dopaminergic neurons within the ventral tegmental area or substantia nigra may be abnormal in psychosis, and exhibit altered relaxometric properties suggesting hyperactivity (Watanabe et al, 2014). The clinical relevance of findings will also have to be studied using a more extensive assessment battery, including those evaluating mood symptoms and cognition.…”