Grant from the Lundbeck Foundations International Neuroscience Programme for Hanne D. Hansen
- Published: Wednesday, 26 September 2018 09:12
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at the Martinos Center at MGH, Boston during the next three years.
The aim of this proposal is to investigate basic pharmacological mechanisms and brain network effects of drugs used in classical and novel treatment of major depressive disorder (MDD). Furthermore, I will identify the effects of different 5-HT2AR agonists on functional brain connectivity which will reveal how intracellular pathways govern brain connectivity.
The classical pharmacological treatment strategy for MDD patients is the administration of SSRIs whereas hallucinogens (5-HT2AR agonists) are currently being investigated for their SSRIs whereas hallucinogens (5-HT2AR agonists) are currently being investigated for their treatment potential in various psychiatric disorders. For both SSRIs and hallucinogens, the mechanism of action is incompletely understood and for the hallucinogens this is further complicated by the fact that these 5-HT2AR agonists can differentially activate intracellular pathways - a phenomenon known as functional selectivity.
I will use hybrid positron emission tomography (PET) and magnetic resonance (MR) neuroimaging to study drug effects in vivo in humans and in non-human primates. In healthy volunteers, I will study the dose-dependent effects of citalopram administration: Changes in neuronal activation and brain circuitries will be measured with MRI and these changes will be related to the serotonin transporter occupancy measured by the PET radioligand [11C]DASB. In non-human primates, we will measure the 5-HT2AR occupancy, the hemodynamic response and changes in brain networks upon administration of two 5-HT2AR agonists: The hallucinogenic 25CN-NBOH and the non-hallucinogenic lisuride.
Identification of brain responses to these two types of anti-depressive drugs will give valuable insight into the spatial and temporal mode of action of these drugs. The outcome of this study will generate critical new information about how the involved brain circuits are affected by the pharmacological intervention and will lay the basis for a personalized medicine approach to patients with MDD.