- Published: Thursday, 03 January 2019 14:42
- Hits: 102
Major grant from the Lundbeck Foundation for 5-year thematic alliance within precision medicine in epilepsy and depression
- Published: Monday, 17 December 2018 14:59
- Hits: 206
Background: Depression and epilepsy constitute frequent and disabling brain disorders. All together, they cripple the daily lives of hundreds of millions of people in today’s society and cause immense socioeconomic problems. About 35% of society’s disease-related costs can be ascribed to brain disorders, with depression accounting for the largest costs. Neuropharmacological interventions are widely used to ameliorate some of these conditions, but quite often, drugs are used in the wrong patients, wrong combinations, or in wrong dosages.
Materials and Methods: In BrainDrugs we will make use of Danish registries to identify associations between intake of brain targeting drugs and clinical outcomes in order to uncover which patient features define a successful antidepressive or antiepileptic drug treatment. To investigate if we can identify patient subgroups, we will conduct advanced text-mining analyses which extract specific clinical features from electronic patient records. Through existing deep phenotyping or genetic databases with biobanks, those features will be related to, e.g., genetic and neuroimaging data to define biologically valid patient subgroups suffering from depression and epilepsy. To increase power to detect biomarkers and treatment response, we will establish new cohorts of patients with epilepsy and depression that we follow longitudinally.
Expected outcome and perspectives: It is our ambition to set the stage for a precision medicine approach in pharmacological treatment of epilepsy and depression, for the benefit of future patients. To succeed in our mission, we have devised a strategy for implementation of research outcomes in the clinic. It is our hope that in the long run, BrainDrugs can serve as a model to be implemented internationally, and for other brain disorders.
A 2-min video pitch of the project can be found here.
Listen to an interview with Gitte on DR P1 Morgen here.
- Published: Monday, 17 December 2018 14:07
- Hits: 138
The defence will take place in Auditorium C, Rigshospitalet Glostrup, Valdemar Hansens Vej 5, 2600 Glostrup.
Chairperson: Professor Steen Gregers Hasselbalch, University of Copenhagen
Opponent: Professor Andrew Charles, UCLA, Los Angeles
Opponent: Associate Professor Andrea Varrone, Karolinska Institute, Stockholm
Principal supervisor: Professor Messoud Ashina, University of Copenhagen
Primary co-supervisor: Professor Gitte Moos Knudsen, University of Copenhagen
Co-supervisor: Anders Hougaard, MD, PhD, Rigshospitalet
Co-supervisor: Hanne Demant Hansen, PhD, Rigshospitalet
Migraine is the most prevalent and disabling neurological disorder worldwide. Since the 1960s serotonin (5-HT) has been implicated in migraine pathophysiology but the exact role of brain serotonin levels in migraine is still unknown. The overall goal of the thesis was to investigate the serotonergic system in the migraine brain using positron emission tomography imaging of two different serotonin receptors.
We used 5-HT4 receptor binding as a biomarker of brain serotonin levels. Based on the serotonin deficiency theory in migraine, we hypothesized that migraine patients would have higher 5-HT4 receptor binding compared to controls. Instead, we found that patients had lower 5-HT4 receptor binding indicating higher brain serotonin levels. However, there was no difference between chronic and episodic migraine patients. This suggests that a high level of brain serotonin is an inherent trait of the migraine brain.
We also investigated 5-HT1B receptor binding in episodic migraine patients and found that they had lower 5-HT1B receptor binding across pain-modulating brain regions compared to controls. During migraine attacks we found that the 5-HT1B receptor binding was reduced compared to outside of attacks, indicating that brain serotonin levels increase during attacks. After treatment with sumatriptan, the 5-HT1B receptor binding decreased further, indicating that sumatriptan binds to central 5-HT1B receptors.
In conclusion, the present thesis supports the hypothesis that the serotonergic system plays a role in migraine pathophysiology, with migraine patients exhibiting high brain serotonin levels between attacks, which increase further during attacks. Further, we show that the 5-HT1B receptor density is altered in migraine patients and provide evidence that sumatriptan may act on central 5-HT1B receptors.
- Published: Wednesday, 03 October 2018 11:55
- Hits: 486
- Published: Wednesday, 26 September 2018 09:12
- Hits: 559
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.
- Published: Monday, 27 August 2018 12:04
- Hits: 651
Liv did a great job at the defense and afterwards NRU celebrated her with a reception.
Liv replying wisely to Kelly Rohan's questions.
- Published: Thursday, 16 August 2018 14:34
- Hits: 723
Professor Lammertsma is world-wide recognized as one of the leading figures within development of PET methodology and its applications for translational experimental medicine across a range of clinical disciplines, but particularly
for brain disorders. He has imposed internationally a culture of rigor for the quantification of regional tissue function using PET.
- Published: Friday, 27 July 2018 12:11
- Hits: 696
- Published: Monday, 02 July 2018 15:30
- Hits: 673
- Published: Tuesday, 12 June 2018 08:56
- Hits: 681
More Articles ...
- NRU Summer Interns
- Grant from DFF to Gitte Moos Knudsen
- Olaf Paulson becomes honorary member of The Danish Neurological Society
- Large grant to Melanie Ganz from the Elsass Foundation
- Two grants to support joint research with Profs Robbins and Sahakian
- Funding from RH
- Funding from Augustinus Fonden
- PhD defence: Vincent Beliveau
- PhD defence: Louise Møller Jørgensen
- Historical EU-funding for NRU post docs