• Gil Leurquin-Sterk
  • Jan Van den Stock
  • Cleo Lina Crunelle
  • Bart de Laat
  • Akila Weerasekera
  • Uwe Himmelreich
  • Guy Bormans
  • Koen Van Laere

Heritable temperament traits have been linked to several neuropsychiatric illnesses, including disorders associated with metabotropic glutamate receptor 5 (mGluR5) and dopaminergic dysfunctions. Considering its modulating effect on neurotransmission, we hypothesized that cerebral mGluR5 availability is associated with temperament traits in healthy humans.

METHODS: Forty-four nonsmoking healthy volunteers (mean age ± SD, 40 ± 14 y; age range, 22-66 y; 22 women) were included in this cross-sectional investigation. Brain mGluR5 availability was quantified on both a voxel-by-voxel and a volume-of-interest basis using the total distribution volume of the radioligand 18F-3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile (18F-FPEB) with 90-min dynamic PET and arterial input function. Moreover, glutamate-glutamine concentrations in the anterior cingulate cortex were measured using MR spectroscopy. These measures were related to the temperament traits of the 240-item Cloninger temperament and character inventory using a regression analysis with age and sex as nuisance variables.

RESULTS: High novelty-seeking temperament was robustly associated with increased mGluR5 availability in various regions including the thalamus (r = 0.71; the strongest association), amygdala, parahippocampus, insula, anterior and posterior cingulate cortex, and several primary sensory areas (all r > 0.58; P < 0.05, corrected for familywise error). These associations were specific because no correlations were found with other temperament scales or with spectroscopic measures of glutamatergic transmission.

CONCLUSION: Overall, these data posit mGluR5 in key paralimbic areas as a strong determinant of the temperament trait novelty seeking. These data add to our understanding of how brain neurochemistry accounts for the variation in human behavior and strongly support further research on mGluR5 as a potential therapeutic target in neuropsychiatric disorders associated with abnormal novelty-seeking behaviors.

Original languageEnglish
Pages (from-to)1746-1752
Number of pages7
JournalJournal of Nuclear Medicine
Issue number11
Publication statusPublished - Nov 2016

    Research areas

  • Adult, Biological Availability, Biomarkers, Exploratory Behavior, Female, Humans, Limbic System, Male, Middle Aged, Molecular Imaging, Nitriles, Organ Specificity, Positron-Emission Tomography, Pyridines, Radiopharmaceuticals, Receptor, Metabotropic Glutamate 5, Reproducibility of Results, Sensitivity and Specificity, Temperament, Tissue Distribution, Young Adult, Journal Article

ID: 38145974