TY - JOUR
T1 - Anatomical relationships between serotonin 5-HT2A and dopamine D2 receptors in living human brain
AU - Ishii, Tatsuya
AU - Kimura, Yasuyuki
AU - Ichise, Masanori
AU - Takahata, Keisuke
AU - Kitamura, Soichiro
AU - Moriguchi, Sho
AU - Kubota, Manabu
AU - Zhang, Ming Rong
AU - Yamada, Makiko
AU - Higuchi, Makoto
AU - Okubo, Yoshinori
AU - Suhara, Tetsuya
N1 - Funding Information:
We thank the radiology technologists in the PET department and the members of the clinical neuroimaging team for their support in the PET scans, Kazuko Suzuki and Shizuko Kawakami for their assistance as clinical coordinators, Hiromi Sano for her support in the MRI scans, and the staff of the molecular probe program for radioligand synthesis and metabolite analysis. Moreover, we thank Sayaka Mizutani (Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology) for her support in the clustering analysis.
Publisher Copyright:
© 2017 Ishii et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2017/12
Y1 - 2017/12
N2 - Serotonin 2A (5-HT2A) receptors and dopamine D2 receptors are intimately related to the physiology and pathophysiology of neuropsychiatric disorders. A large number of studies have reported the effectiveness of psychotropic agents targeting 5-HT2A and D2 receptors in these disorders. In addition to the individual functions of these receptors, the interaction between the two neurotransmitter systems has been studied in the living brain. However, little is known about their regional relationship in individual human brains. We investigated regional relationships between 5-HT2A and D2 receptors using positron emission tomography (PET) and a bicluster analysis of the correlation matrix of individual variation in the two receptor densities to identify groups of distinctive regional correlations between the two receptors. Methods: Seven healthy volunteers underwent PET scans with [18F]altanserin and [11C]FLB 457 for 5-HT2A and D2 receptors, respectively. As a measure of receptor density, a binding potential (BP) was calculated from PET data for 76 cerebral cortical regions. A correlation matrix was calculated between the binding potentials of [18F]altanserin and [11C]FLB 457 for those regions. The regional relationships were investigated using a bicluster analysis of the correlation matrix with an iterative signature algorithm. Results: We identified two clusters of regions. The first cluster identified a distinct profile of correlation coefficients between 5-HT2A and D2 receptors, with the former in regions related to sensorimotor integration (supplementary motor area, superior parietal gyrus, and paracentral lobule) and the latter in most cortical regions. The second cluster identified another distinct profile of correlation coefficients between 5-HT2A receptors in the bilateral hippocampi and D2 receptors in most cortical regions. Conclusions: The observation of two distinct clusters in the correlation matrix suggests regional interactions between 5-HT2A and D2 receptors in sensorimotor integration and hippocampal function. A bicluster analysis of the correlation matrix of these neuroreceptors may be beneficial in understanding molecular networks in the human brain.
AB - Serotonin 2A (5-HT2A) receptors and dopamine D2 receptors are intimately related to the physiology and pathophysiology of neuropsychiatric disorders. A large number of studies have reported the effectiveness of psychotropic agents targeting 5-HT2A and D2 receptors in these disorders. In addition to the individual functions of these receptors, the interaction between the two neurotransmitter systems has been studied in the living brain. However, little is known about their regional relationship in individual human brains. We investigated regional relationships between 5-HT2A and D2 receptors using positron emission tomography (PET) and a bicluster analysis of the correlation matrix of individual variation in the two receptor densities to identify groups of distinctive regional correlations between the two receptors. Methods: Seven healthy volunteers underwent PET scans with [18F]altanserin and [11C]FLB 457 for 5-HT2A and D2 receptors, respectively. As a measure of receptor density, a binding potential (BP) was calculated from PET data for 76 cerebral cortical regions. A correlation matrix was calculated between the binding potentials of [18F]altanserin and [11C]FLB 457 for those regions. The regional relationships were investigated using a bicluster analysis of the correlation matrix with an iterative signature algorithm. Results: We identified two clusters of regions. The first cluster identified a distinct profile of correlation coefficients between 5-HT2A and D2 receptors, with the former in regions related to sensorimotor integration (supplementary motor area, superior parietal gyrus, and paracentral lobule) and the latter in most cortical regions. The second cluster identified another distinct profile of correlation coefficients between 5-HT2A receptors in the bilateral hippocampi and D2 receptors in most cortical regions. Conclusions: The observation of two distinct clusters in the correlation matrix suggests regional interactions between 5-HT2A and D2 receptors in sensorimotor integration and hippocampal function. A bicluster analysis of the correlation matrix of these neuroreceptors may be beneficial in understanding molecular networks in the human brain.
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U2 - 10.1371/journal.pone.0189318
DO - 10.1371/journal.pone.0189318
M3 - Article
C2 - 29220382
AN - SCOPUS:85037659201
SN - 1932-6203
VL - 12
JO - PLoS One
JF - PLoS One
IS - 12
M1 - e0189318
ER -
