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The serotonin (5-HT) system modulates many important brain functions and is critically involved in many neuropsychiatric disorders. We here present a high-resolution multi-dimensional in vivo atlas of four of the human brain's 5-HT receptors (5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4) as well as of the 5-HT transporter (5-HTT). The atlas is created from molecular and structural high-resolution neuroimaging data consisting of Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) scans, acquired in a total of 210 healthy individuals. Comparison of the regional PET binding measures with postmortem human brain autoradiography outcomes showed a high correlation for the five 5-HT targets and this enabled us to transform the atlas to represent protein densities (pmol/ml). We also assessed the regional association between protein concentration and mRNA expression in the human brain by comparing the 5-HT density across the atlas to data from the Allen Human Brain atlas and identified receptor- and transporter specific associations which inform about the regional relation between the two measures. Together, these data provide unparalleled insight into the serotonin system of the human brain.SIGNIFICANCE STATEMENTWe present a high-resolution PET and MR-based human brain atlas of important serotonin receptors and the transporter. The regional PET-derived binding measures correlate strongly with the corresponding autoradiography protein levels. The strong correlation enables the transformation of the PET-derived human brain atlas into a protein density map of the 5-HT system. Next, we compared the regional receptor/transporter protein densities to mRNA levels, and uncovered unique associations between protein expression and density at high detail. This new in vivo neuroimaging atlas of the 5-HT system does not only provide insight in the human brain's regional protein synthesis, transport and density, but also represents a valuable source of information for the neuroscience community as a comparative instrument to assess brain disorders.

A High-Resolution In Vivo Atlas of the Human Brain's Serotonin System