Building a Center for Excellent Research in Mental Disorders

1. Bygging av Senter for Fremragende Forskning Ole A. AndreassenSFF NORMENT, KG Jebsen Senter for PsykoseforskningInstitutt for klinisk medisin, Universitetet i Oslo, Nydalen DPS, Klinikk psykisk helse og avhengighet, Oslo universitetssykehus,

3. Innhold • Bakgrunn • Planlegging • Arbeid

4. Faglig bakgrunn

6. 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

7. Deltakere

8. Translational Team Multidisciplinary – complementary expertise Ole A. AndreassenIngrid Melle Srdjan Djurovic Ingrid Agartz Kjetil Sundet Stephanie Le Hellard Vidar M. Steen Kenneth Hugdahl Oslo Univ. Hospital, Univ. Oslo, Univ. Bergen,

9. Deltakere • Hvordan velge? Ikke formell utnevnelse • Må kjenne hverandre, ikke ad hoc • Må være komplementære • Ikke søknadspynt – avsløres (og vanskelig å gjennomføre) • Virtuelt senter?

10. Organisering

12. NORMENT • Norwegian Center for Mental Disorders Research • TOP bygget, Ullevål sykehus, OUS • UIO, OUS, UIB http://www.med.uio.no/norment/

13. Scientific vision for NORMENT • Disease mechanisms • Tools for outcome prediction • Severe mental illness • Schizophrenia • Bipolar disorder • New approach • Norwegian advantage • Vertical synergy

14. Added value of NORMENT Vertical synergy Norwegian advantage Environment SCZ Outcome Mortality Prodrome BIP Clinical phenotypes Brain phenotypes Genes Animal models Cell cultures

15. Organisation NORMENT Director Core Researchers Clinical Cognitive Brain Imaging Funct. Genomics Biostat , Biobank Projects across Intern. Guest Researchers Collaborators

16. Praktisk arbeid søknad • Drivere • Synergi • Fremtidsmuligheter

17. Premisser • Felles prosjekt • Naturlige forutsetninger • struktur, kompetanse • Nye metoder, unike bidrag • Ikke mer av det samme, men kan videreutvikle det beste • Kjøttvekt

18. Viktige spørsmål • Hva er unikt? • Hva gir synergi – merverdi? • Vitenskap og metode integrert

19. Praktisk • 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

20. Status

21. Multidisciplinary research Work Units Projects

22. Scientific production 2015 • 7 PhD degrees • PubMed pubs n=124 • Impact factor (IF) • Co-publications

23. Patients • Prototypical human • Clinical departments - OUS • Catchment area • Clinical interest – future strategy

24. No relapse One relapse Fig. 3. Change in verbal learning performance, comparing CVLT measures at baseline with 1-year, 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 Trajectories > 2 relapses

26. 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

27. Brain Imaging (3T scanners)Large-scale cortical network dynamics (working memory) across disorders Brandt, Kaufmann, Agartz, Hugdahl, Jensen, Melle, Andreassen, Westlye. In review

28. Biophysical psychiatry • Mäki-Marttunen et al. in prep

29. 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 den-drites used for functional imaging. Bottom: Time-courses of Ca2+ response from regions color-coded on top. Devor et al.

30. Big data GeneticsPrediction from 1 000 000 SNPs Yanget al. Submitted

31. 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)

32. Improved Prediction of Phenotypic Variance SCZ Dale et al. In prep

33. NORMENT Sept 2014

34. NORMENT Sept 2014 NORMENT • Approx 80 positions 2016

35. Thanks • Participants in the studies • Research team and collaborators • Funding agencies • Research Council of Norway • KG Jebsen Foundation • Oslo University Hospital • University of Oslo, University of Bergen • Regional Health Authorities • EU, NIH