Common HTR2A variants and 5-HTTLPR are not associated with human in vivo serotonin 2A receptor levels
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Common HTR2A variants and 5-HTTLPR are not associated with human in vivo serotonin 2A receptor levels. / Spies, Marie; Nasser, Arafat; Ozenne, Brice; Jensen, Peter S.; Knudsen, Gitte M.; Fisher, Patrick M.
In: Human Brain Mapping, Vol. 41, No. 16, 2020, p. 4518-4528.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Common HTR2A variants and 5-HTTLPR are not associated with human in vivo serotonin 2A receptor levels
AU - Spies, Marie
AU - Nasser, Arafat
AU - Ozenne, Brice
AU - Jensen, Peter S.
AU - Knudsen, Gitte M.
AU - Fisher, Patrick M.
PY - 2020
Y1 - 2020
N2 - The serotonin 2A receptor (5-HT2AR) is implicated in the pathophysiology and treatment of various psychiatric disorders. [18F]altanserin and [11C]Cimbi-36 positron emission tomography (PET) allow for high-resolution imaging of 5-HT2AR in the living human brain. Cerebral 5-HT2AR binding is strongly genetically determined, though the impact of specific variants is poorly understood. Candidate gene studies suggest that HTR2A single nucleotide polymorphisms including rs6311/rs6313, rs6314, and rs7997012 may influence risk for psychiatric disorders and mediate treatment response. Although known to impact in vitro expression of 5-HT2AR or other serotonin (5-HT) proteins, their effect on human in vivo brain 5-HT2AR binding has as of yet been insufficiently studied. We thus assessed the extent to which these variants and the commonly studied 5-HTTLPR predict neocortex in vivo 5-HT2AR binding in healthy adult humans. We used linear regression analyses and likelihood ratio tests in 197 subjects scanned with [18F]altanserin or [11C]Cimbi-36 PET. Although we observed genotype group differences in 5-HT2AR binding of up to ~10%, no genetic variants were statistically significantly predictive of 5-HT2AR binding in what is the largest human in vivo 5-HT2AR imaging genetics study to date. Thus, in vitro and post mortem results suggesting effects on 5-HT2AR expression did not carry over to the in vivo setting. To any extent these variants might affect clinical risk, our findings do not support that 5-HT2AR binding mediates such effects. Our observations indicate that these individual variants do not significantly contribute to genetic load on human in vivo 5-HT2AR binding.
AB - The serotonin 2A receptor (5-HT2AR) is implicated in the pathophysiology and treatment of various psychiatric disorders. [18F]altanserin and [11C]Cimbi-36 positron emission tomography (PET) allow for high-resolution imaging of 5-HT2AR in the living human brain. Cerebral 5-HT2AR binding is strongly genetically determined, though the impact of specific variants is poorly understood. Candidate gene studies suggest that HTR2A single nucleotide polymorphisms including rs6311/rs6313, rs6314, and rs7997012 may influence risk for psychiatric disorders and mediate treatment response. Although known to impact in vitro expression of 5-HT2AR or other serotonin (5-HT) proteins, their effect on human in vivo brain 5-HT2AR binding has as of yet been insufficiently studied. We thus assessed the extent to which these variants and the commonly studied 5-HTTLPR predict neocortex in vivo 5-HT2AR binding in healthy adult humans. We used linear regression analyses and likelihood ratio tests in 197 subjects scanned with [18F]altanserin or [11C]Cimbi-36 PET. Although we observed genotype group differences in 5-HT2AR binding of up to ~10%, no genetic variants were statistically significantly predictive of 5-HT2AR binding in what is the largest human in vivo 5-HT2AR imaging genetics study to date. Thus, in vitro and post mortem results suggesting effects on 5-HT2AR expression did not carry over to the in vivo setting. To any extent these variants might affect clinical risk, our findings do not support that 5-HT2AR binding mediates such effects. Our observations indicate that these individual variants do not significantly contribute to genetic load on human in vivo 5-HT2AR binding.
KW - 5-HTTLPR
KW - positron emission tomography
KW - serotonin 2A receptor
KW - single nucleotide polymorphism
U2 - 10.1002/hbm.25138
DO - 10.1002/hbm.25138
M3 - Journal article
C2 - 32697408
AN - SCOPUS:85088316308
VL - 41
SP - 4518
EP - 4528
JO - Human Brain Mapping
JF - Human Brain Mapping
SN - 1065-9471
IS - 16
ER -
ID: 245658954