Genetic contributions to brain serotonin transporter levels in healthy adults
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Genetic contributions to brain serotonin transporter levels in healthy adults. / Bruzzone, Silvia Elisabetta Portis; Nasser, Arafat; Aripaka, Sagar Sanjay; Spies, Marie; Ozenne, Brice; Jensen, Peter Steen; Knudsen, Gitte Moos; Frokjaer, Vibe Gedsoe; Fisher, Patrick Mac Donald.
In: Scientific Reports, Vol. 13, No. 1, 16426, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Genetic contributions to brain serotonin transporter levels in healthy adults
AU - Bruzzone, Silvia Elisabetta Portis
AU - Nasser, Arafat
AU - Aripaka, Sagar Sanjay
AU - Spies, Marie
AU - Ozenne, Brice
AU - Jensen, Peter Steen
AU - Knudsen, Gitte Moos
AU - Frokjaer, Vibe Gedsoe
AU - Fisher, Patrick Mac Donald
N1 - Publisher Copyright: © 2023, Springer Nature Limited.
PY - 2023
Y1 - 2023
N2 - The serotonin transporter (5-HTT) critically shapes serotonin neurotransmission by regulating extracellular brain serotonin levels; it remains unclear to what extent 5-HTT levels in the human brain are genetically determined. Here we applied [11C]DASB positron emission tomography to image brain 5-HTT levels and evaluated associations with five common serotonin-related genetic variants that might indirectly regulate 5-HTT levels (BDNF rs6265, SLC6A4 5-HTTLPR, HTR1A rs6295, HTR2A rs7333412, and MAOA rs1137070) in 140 healthy volunteers. In addition, we explored whether these variants could predict in vivo 5-HTT levels using a five-fold cross-validation random forest framework. MAOA rs1137070 T-carriers showed significantly higher brain 5-HTT levels compared to C-homozygotes (2–11% across caudate, putamen, midbrain, thalamus, hippocampus, amygdala and neocortex). We did not observe significant associations for the HTR1A rs6295 and HTR2A rs7333412 genotypes. Our previously observed lower subcortical 5-HTT availability for rs6265 met-carriers remained in the presence of these additional variants. Despite this significant association, our prediction models showed that genotype moderately improved prediction of 5-HTT in caudate, but effects were not statistically significant after adjustment for multiple comparisons. Our observations provide additional evidence that serotonin-related genetic variants modulate adult human brain serotonin neurotransmission.
AB - The serotonin transporter (5-HTT) critically shapes serotonin neurotransmission by regulating extracellular brain serotonin levels; it remains unclear to what extent 5-HTT levels in the human brain are genetically determined. Here we applied [11C]DASB positron emission tomography to image brain 5-HTT levels and evaluated associations with five common serotonin-related genetic variants that might indirectly regulate 5-HTT levels (BDNF rs6265, SLC6A4 5-HTTLPR, HTR1A rs6295, HTR2A rs7333412, and MAOA rs1137070) in 140 healthy volunteers. In addition, we explored whether these variants could predict in vivo 5-HTT levels using a five-fold cross-validation random forest framework. MAOA rs1137070 T-carriers showed significantly higher brain 5-HTT levels compared to C-homozygotes (2–11% across caudate, putamen, midbrain, thalamus, hippocampus, amygdala and neocortex). We did not observe significant associations for the HTR1A rs6295 and HTR2A rs7333412 genotypes. Our previously observed lower subcortical 5-HTT availability for rs6265 met-carriers remained in the presence of these additional variants. Despite this significant association, our prediction models showed that genotype moderately improved prediction of 5-HTT in caudate, but effects were not statistically significant after adjustment for multiple comparisons. Our observations provide additional evidence that serotonin-related genetic variants modulate adult human brain serotonin neurotransmission.
U2 - 10.1038/s41598-023-43690-x
DO - 10.1038/s41598-023-43690-x
M3 - Journal article
C2 - 37777558
AN - SCOPUS:85173747656
VL - 13
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 16426
ER -
ID: 370472255