Implications of serotonin transporter distribution in the healthy and diseased human brain, investigated by positron emission tomography

......................................................................................................................................................... v Kurzfassung ................................................................................................................................................... vi Publications arising from this thesis ............................................................................................................ viii Acknowledgments and project funding ........................................................................................................ ix I. BACKGROUND ............................................................................................................................. 1 1.1. General introduction ............................................................................................................................. 1 1.2. The serotonin transporter (SERT) and its role in psychiatry and psychopharmacological treatment .. 2 1.2.1. SERT structure and function .................................................................................................. 2 1.2.2. SERT regulation ...................................................................................................................... 5 1.2.3. SERT blockage in relation to antidepressant treatment ....................................................... 7 1.3. Quantification of the brain SERT with PET and [C]DASB..................................................................... 9 1.3.1. PET and SPECT to study the SERT .......................................................................................... 9 1.3.2. PET and SPECT radiopharmaceuticals for the SERT............................................................. 11 1.3.3. Quantitative data analysis ................................................................................................... 12 1.4. Imaging the SERT in the healthy and diseased human brain .............................................................. 16 1.4.1. SERT distribution in the human brain.................................................................................. 16 1.4.2. Imaging the SERT in psychiatric disorders ........................................................................... 18 1.4.3. SERT occupancy measured with PET and its relation to treatment outcome..................... 20 1.5. Open questions .................................................................................................................................... 21 II. AIMS OF THE THESIS .................................................................................................................. 23 III. RESULTS .................................................................................................................................... 24 3.1. First publication: Cerebral Serotonin Transporter Asymmetry in Females, Males and Male-to-Female Transsexuals measured by PET in vivo ..................................................................... 24 3.1.1. Abstract ............................................................................................................................... 25 3.1.2. Introduction ......................................................................................................................... 26 3.1.3. Material and methods ......................................................................................................... 28 3.1.4. Results ................................................................................................................................. 30 3.1.5. Discussion ............................................................................................................................ 34 3.1.6. Conclusions .......................................................................................................................... 38 3.1.7. References ........................................................................................................................... 39