Fondsbørsvekselerer Henry Hansen og Hustru Karla Hansens Legat

Congratulations to NRU senior researcher Lars H. Pinborg, who has received the 'Fondsbørsvekselerer Henry Hansen og Hustru Karla Hansens Legat' worth 350.000 DKK for his research in preoperative diagnosis of patients examined for epilepsy surgery. The award has been given based on a recommendation from an advisory committee at the University of Copenhagen.

New FSS grants to NRU researchers

Congratulations to Louise Møller Jørgensen for receiving from the Independent Research Fund Denmark (FSS) a Clinician Scientist Position grant worth 1.039.248 DKK for her part-time research project "Deep Brain Stimulation: Effects on cerebral blood flow, brain circuits and neurotransmission". Also, congratulations to Gitte Moos Knudsen for receiving a scholar stipend grant worth 103.100 DKK for the project "Neural correlates of the personality dimension openness to experience: a resting state fMRI study in healthy participants".

Major grant from the Lundbeck Foundation for 5-year thematic alliance within precision medicine in epilepsy and depression

Professor Gitte Moos Knudsen, head of NRU, has received a major grant worth 40 million Danish kroner from the Lundbeck Foundation for a highly ambitious thematic alliance called BrainDrugs. Perfectly aligned with the National Strategy for Personalized Medicine 2017-2020, the aim of the new thematic alliance is to establish which key features predict drug response in patients with epilepsy or depression. The BrainDrugs consortium is composed of a multidisciplinary team of experienced investigators from The Capital Region, Aarhus and the specialized epilepsy hospital Filadelfia, assisted by two international experts within the field. The project will start July 1st, 2019 and run for five years.

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.

PhD defence: Marie Deen

On Friday, January 4, at 2 PM, Marie Deen, MD, will defend her PhD dissertation entitled "PET investigations of brain serotonin receptor binding in  migraine patients".

The defence will take place in Auditorium C, Rigshospitalet Glostrup, Valdemar Hansens Vej 5, 2600 Glostrup.

Assessment committee:
Chairperson: Professor Steen Gregers Hasselbalch, University of Copenhagen
Opponent: Professor Andrew Charles, UCLA, Los Angeles
Opponent: Associate Professor Andrea Varrone, Karolinska Institute, Stockholm

Academic advisors:
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.

Travel stipend for Giske Opheim

Congratulations to Giske Opheim for receiving DKK 19,253 from Lennart Grams Mindefond for her participation at the 72nd Annual Meeting of the American Epilepsy Society in New Orleans (Nov 30-Dec 4, 2018).

Grant from the Lundbeck Foundations International Neuroscience Programme for Hanne D. Hansen

Congratulations to Hanne for receiving 2.9 mio DKK from the Lundbeck Foundation to conduct the project 'Characterizing brain network effects of novel and existing drugs using hybrid PET/MR imaging'
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.

Adriaan Lammertsma new visiting professor at NRU

Gitte Moos Knudsen has received 750.000 DKK from the Lundbeck Foundation for a visiting professorship for Professor Adriaan Lammertsma from Department of Nuclear Medicine and PET Research, Amsterdam, Netherlands.

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.

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NRU annual report 2017

The 2017 NRU annual report has been published and is available for download here.

Three travel stipends from the Lundbeck Foundation

The Lundbeck Foundation has granted three travel stipends to NRU: Martin Korsbak Madsen received 25.410 DKK for the course 'Learning the Conn Toolbox' which he attended in Boston in April, Martin Nørgaard 8.003 DKK for the PRNI 2018 that took place in Singapore in June and finally, Hanne D Hansen 9.695 DKK for the NRM2018 taking place in London this July.