Positive Association Between Limbic Metabotropic Glutamate Receptor 5 Availability and Novelty-Seeking Temperament in Humans: An 18F-FPEB PET Study.
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 radioligand18F-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.


CONCLUSIONS
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.
Department of Nuclear Medicine and Molecular Imaging, University Hospitals Leuven, Leuven, Belgium gil.leurquin-sterk@uzleuven.be.
Gil
G
Leurquin-Sterk
Laboratory for Translational Neuropsychiatry, Department of Neurosciences, KU Leuven and Department of Old Age Psychiatry, University Hospitals Leuven, Leuven, Belgium.
Jan
J
Van den Stock
Toxicological Center, University of Antwerp, Wilrijk, Belgium.
Cleo Lina
CL
Crunelle
Department of Nuclear Medicine and Molecular Imaging, University Hospitals Leuven, Leuven, Belgium.|MoSAIC, Molecular Small Animal Imaging Center, KU Leuven, Leuven, Belgium.
Bart
B
de Laat
Biomedical MRI/MoSAIC, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium; and.
Akila
A
Weerasekera
Biomedical MRI/MoSAIC, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium; and.
Uwe
U
Himmelreich
Laboratory for Radiopharmacy, KU Leuven, Leuven, Belgium.
Guy
G
Bormans
Department of Nuclear Medicine and Molecular Imaging, University Hospitals Leuven, Leuven, Belgium.|MoSAIC, Molecular Small Animal Imaging Center, KU Leuven, Leuven, Belgium.
Koen
K
Van Laere
D000328:Adult; D001682:Biological Availability; D015415:Biomarkers / Q000378:metabolism; D005106:Exploratory Behavior / Q000502:physiology*; D005260:Female; D006801:Humans; D008032:Limbic System / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D057054:Molecular Imaging / Q000379:methods; D009570:Nitriles / Q000493:pharmacokinetics*; D009928:Organ Specificity; D049268:Positron-Emission Tomography / Q000379:methods*; D011725:Pyridines / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D064529:Receptor, Metabotropic Glutamate 5 / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013694:Temperament / Q000502:physiology*; D014018:Tissue Distribution; D055815:Young Adult
C527000:3-fluoro-5-((pyridin-3-yl)ethynyl)benzonitrile; D015415:Biomarkers; C578935:GRM5 protein, human; D009570:Nitriles; D011725:Pyridines; D019275:Radiopharmaceuticals; D064529:Receptor, Metabotropic Glutamate 5
18F-FPEB; mGluR5; neuroimaging; novelty seeking; personality