Gil Leurquin-Sterk1, Jan Van den Stock2, Cleo Lina Crunelle3, Bart de Laat4,5, Akila Weerasekera6, Uwe Himmelreich6, Guy Bormans7, Koen Van Laere4,5. 1. Department of Nuclear Medicine and Molecular Imaging, University Hospitals Leuven, Leuven, Belgium gil.leurquin-sterk@uzleuven.be. 2. Laboratory for Translational Neuropsychiatry, Department of Neurosciences, KU Leuven and Department of Old Age Psychiatry, University Hospitals Leuven, Leuven, Belgium. 3. Toxicological Center, University of Antwerp, Wilrijk, Belgium. 4. Department of Nuclear Medicine and Molecular Imaging, University Hospitals Leuven, Leuven, Belgium. 5. MoSAIC, Molecular Small Animal Imaging Center, KU Leuven, Leuven, Belgium. 6. Biomedical MRI/MoSAIC, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium; and. 7. Laboratory for Radiopharmacy, KU Leuven, Leuven, Belgium.
Abstract
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.
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.
Authors: Sophie E Holmes; Matthew J Girgenti; Margaret T Davis; Robert H Pietrzak; Nicole DellaGioia; Nabeel Nabulsi; David Matuskey; Steven Southwick; Ronald S Duman; Richard E Carson; John H Krystal; Irina Esterlis Journal: Proc Natl Acad Sci U S A Date: 2017-07-17 Impact factor: 11.205
Authors: Adrienne Müller Herde; Yoan Mihov; Stefanie D Krämer; Linjing Mu; Antoine Adamantidis; Simon M Ametamey; Gregor Hasler Journal: Neurotox Res Date: 2019-05-22 Impact factor: 3.911
Authors: Jenny Ceccarini; Gil Leurquin-Sterk; Cleo Lina Crunelle; Bart de Laat; Guy Bormans; Hendrik Peuskens; Koen Van Laere Journal: J Nucl Med Date: 2019-09-03 Impact factor: 10.057
Authors: Adam P Mecca; Kelly Rogers; Zachary Jacobs; Julia W McDonald; Hannah R Michalak; Nicole DellaGioia; Wenzhen Zhao; Ansel T Hillmer; Nabeel Nabulsi; Keunpoong Lim; Jim Ropchan; Yiyun Huang; David Matuskey; Irina Esterlis; Richard E Carson; Christopher H van Dyck Journal: Neuroimage Date: 2021-05-27 Impact factor: 7.400