Genetic contributions to brain serotonin transporter levels in healthy adults
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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.
Original language | English |
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Article number | 16426 |
Journal | Scientific Reports |
Volume | 13 |
Issue number | 1 |
Number of pages | 11 |
ISSN | 2045-2322 |
DOIs | |
Publication status | Published - 2023 |
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