Bygging av Senter for Fremragende
Forskning
Ole A. Andreassen
SFF NORMENT, KG Jebsen Senter for Psykoseforskning
Institutt for klinisk medisin, Universitetet i Oslo,
Nydalen DPS, Klinikk psykisk helse og avhengighet, Oslo universitetssykehus,
Innhold
• Bakgrunn
• Planlegging
• Arbeid
Faglig bakgrunn
Ukjente sykdomsmekanismer
• Diagnose – deskriptive kriterier
• Medikasjon oppdaget ved tilfeldighet
• Vanskelig (umulig) med primær
forebygging – uspesifikke premorbid
sykdomsmarkører
• Hva vi vet:
– Høy heritabilitet
– Hjernesykdommer
– Økt dødelighet
Deltakere
Translational Team
Multidisciplinary – complementary expertise
Ole A. Andreassen
Ingrid Agartz
Kjetil Sundet
Ingrid Melle
Srdjan Djurovic
Stephanie Le Hellard Vidar M. Steen Kenneth Hugdahl
Oslo Univ. Hospital, Univ. Oslo, Univ. Bergen,
Deltakere
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Hvordan velge? Ikke formell utnevnelse
Må kjenne hverandre, ikke ad hoc
Må være komplementære
Ikke søknadspynt – avsløres (og
vanskelig å gjennomføre)
• Virtuelt senter?
Organisering
NORMENT
• Norwegian Center for Mental Disorders Research
• TOP bygget,
Ullevål sykehus, OUS
• UIO, OUS, UIB
http://www.med.uio.no/norment/
Scientific vision for NORMENT
• Disease mechanisms
• Tools for outcome prediction
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• Severe mental illness
– Schizophrenia
– Bipolar disorder
• New approach
– Norwegian advantage
– Vertical synergy
Added value of NORMENT
Vertical synergy
Norwegian advantage
Environment
SCZ
Prodrome
BIP
Clinical phenotypes
Brain phenotypes
Genes
Animal models
Cell cultures
Outcome
Mortality
Organisation NORMENT
Cognitive
Clinical
Collaborators
Brain Imaging
Intern. Guest Researchers
Funct. Genomics
Projects across
Core Researchers
Director
Biostat , Biobank
Praktisk arbeid søknad
• Drivere
• Synergi
• Fremtidsmuligheter
Premisser
• Felles prosjekt
• Naturlige forutsetninger
– struktur, kompetanse
• Nye metoder, unike bidrag
• Ikke mer av det samme, men kan
videreutvikle det beste
• Kjøttvekt
Viktige spørsmål
• Hva er unikt?
• Hva gir synergi – merverdi?
• Vitenskap og metode integrert
Praktisk
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Langsiktig satsing – flere år
Konsept, ide og sentrale forskere –
Synergi
Ellers mye «grantology» - sideantall,
papers på CV, kvinneandel etc. - enkelt
• Vanskelig med detaljer i 10 år
• Mye tid – men kan brukes i andre
sammenhenger
Status
Multidisciplinary research
Work Units
Projects
Scientific production 2015
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7 PhD degrees
PubMed pubs n=124
Impact factor (IF)
Co-publications
Patients
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Prototypical human
Clinical departments - OUS
Catchment area
Clinical interest – future strategy
Trajectories
0,8
0,7
0,6
No relapse
z-scores (CVLT)
0,5
0,4
0,3
One relapse
0,2
0,1
0
> 2 relapses
-0,1
-0,2
Baseline
1-year
2-years (.
..) 5-years
Fig. 3. Change in verbal learning performance, comparing CVLT measures at baseline with 1year, 2-year and 5 year follow-ups, for patients grouped according to severity of illness (number
of relapses in the 5-year period).
Barder et al. Schizoph Res 2013
BD2K: Big Data NORMENT
• Clinical database (SQL)
– 1400 variables from n=3000 individuals
• Brain Imaging (linux system OUS)
– 300 000 voxels per brain, n=2600 individuals
• Genotypes (aim: «Half % Norway»)
– Genomewide chipping: 1 mill SNPs, n=25 000
• Sensitive data
• Apps – still political problems
Brain Imaging (3T scanners)
Large-scale cortical network dynamics (working memory) across disorders
Brandt, Kaufmann, Agartz, Hugdahl, Jensen,
Melle, Andreassen, Westlye. In review
Biophysical psychiatry
Mäki-Marttunen et al. in prep
Stem cells
In vivo imaging of activity in iPSC-derived human neurons transplanted into mouse cerebral cortex. A. 2-photon maximal
intensity projection through the cell bodies (~200 mm deep) and basal dendrites of the transplanted human neurons at 12
months. B. Side projections of the apical dendrites for the same neurons. C. High resolution images of spiny dendrites in
layer I. The red marker is SR101. D. 2-photon field of view with a cluster of human neurons stained with calcium
indicator OGB1 and a micropipette used to deliver glutamate puffs. E. Top: Region of interest (ROI) with human dendrites used for functional imaging. Bottom: Time-courses of Ca2+ response from regions color-coded on top. Devor et al.
Big data Genetics
Prediction from 1 000 000 SNPs
Yang et al. Submitted
Predict outcome and course
• Define trajectories
– 4000 patients – follow up, repeated assessments
(Melle et al. Arch Gen Psychiatry 2008)
• Causes of increased mortality
– Clinical characteristics and follow up
• Register information
– Genes, MRI, environment, clinical characteristics
(Aas et al Schizophr Bull 2011)
Improved Prediction of Phenotypic Variance SCZ
Dale et al. In prep
NORMENT Sept 2014
NORMENT Sept 2014
NORMENT
• Approx 80 positions 2016
Thanks
• Participants in the studies
• Research team and collaborators
• Funding agencies
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Research Council of Norway
KG Jebsen Foundation
Oslo University Hospital
University of Oslo, University of Bergen
Regional Health Authorities
EU, NIH