third-generation neuroimaging: translating the research ... 2013/borgwardt-ppt.pdf ·...
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Third-generation neuroimaging:
Translating the research evidence
into clinical utility
Stefan Borgwardt Department of Psychiatry, University of Basel Institute of Psychiatry, King’s College London
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Clinical Neuroimaging
› Tissue-specific parameters: › - T1 › - Protone density (PD) › - T2/T2*
› Scanning – parameters:
› - Repetition Time (TR) › - Pulse (TE)
| 2 30. Juli 2013 Universitäre Psychiatrische Kliniken Basel | www.upkbs.ch |
T1 PD T2
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| 3 Universitäre Psychiatrische Kliniken Basel | www.upkbs.ch |
Ventricular enlargement in schizophrenia
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From clinical towards second-generation neuroimaging
| 4 Universitäre Psychiatrische Kliniken Basel | www.upkbs.ch |
› Simple structural brain alterations associated with the neurobiology of the illness (computerised tomography (CT) to investigate brain size abnormalities etc)
› More sophisticated techniques: whole-brain automated methods (voxel-based morphometry), white-matter methods (diffusion tensor imaging, tractography)
› Functional methods (functional magnetic resonance imaging, fMRI)
› Advanced neurochemical and pharmacological imaging (PET techniques addressing receptor bindings and pre-/post-synaptic functions, magnetic resonance spectroscopy, MRS)
› Multimodal approaches
› Multi-center analyses and meta-analytical imaging methods
Meyer-Lindenberg A and Weinberger DR Nat Rev Neurosci. 2006 7:818-–27.
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Genotype – Endophenotype - Phenotype
| 5 Universitäre Psychiatrische Kliniken Basel | www.upkbs.ch |
Nat Rev Neurosci: 2006 Oct;7(10):818-27.
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Current state
| 6 Universitäre Psychiatrische Kliniken Basel | www.upkbs.ch |
• No consistent or reliable anatomical or functional alterations have
been unequivocally associated with psychosis or schizophrenia
• No clinical applications have been developed in psychiatric
neuroimaging
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Staging model of schizophrenia
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Model of psychosis onset from clinical high-risk state
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| 9 Universitäre Psychiatrische Kliniken Basel | www.upkbs.ch |
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Meta-Analysis of cognitive functioning in prodromal psychosis
High-risk (HR) vs. controls HR with transition vs. without transition
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Progressive gray matter volume reductions in ARMS with later transition to psychosis (VBM)
| 11 Universitäre Psychiatrische Kliniken Basel | www.upkbs.ch |
ARMS-T: L PHP, OF, Cerebellum; Bilateral: CC
ARMS-T: OF, SFG, ITG, SPC, MPC, Cerebellum
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Gray matter abnormalities before the onset of psychosis
| 12 Universitäre Psychiatrische Kliniken Basel | www.upkbs.ch |
ARMS vs. Controls: GM reduction mediotemporal and prefrontal
ARMS-T vs. ARMS-NT: GM reduction inferior frontal, superior temporal und insula
Borgwardt SJ et al. Br J Psychiatry Suppl. 2007;51:s69-75.
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| 13 Universitäre Psychiatrische Kliniken Basel | www.upkbs.ch |
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| 14 Universitäre Psychiatrische Kliniken Basel | www.upkbs.ch |
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Voxel-based meta-analysis of vulnerability to psychosis (Control: n=746, HR: n=920)
| 15 Universitäre Psychiatrische Kliniken Basel | www.upkbs.ch |
GM reductions in HR: STG, ACC, Hippocampus/PHG
Converters: reduced STG and IFG
ACC: Anterior cingulate cortex; GM: Gray matter; PHG: parahippocampal gyrus; STG: Superior temporal gyrus.
Fusar-Poli P et al. Neurosci Biobehav Rev 2011 ;35(5):1175–85.
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| 16 Universitäre Psychiatrische Kliniken Basel | www.upkbs.ch |
Antipsychotic drugs could shrink patients' brains
7 February 2011 | Nature | doi:10.1038/news.2011.75
More antipsychotic was associated with smaller GM. Illness severity had relatively modest correlations with tissue volume reduction, and alcohol/illicit drug misuse had no significant associations when effects of the other variables were adjusted.
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Voxel-based meta-analysis of vulnerability and onset related gray matter abnormalities in psychosis
| 17 Universitäre Psychiatrische Kliniken Basel | www.upkbs.ch |
n= 198 antipsychotic-naive high risk (HR) n= 206 antipsychotic-naive first-episode psychosis (FEP) n=254 controls
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Voxel-based meta-analysis of vulnerability and onset related gray matter abnormalities in psychosis
| 18 Universitäre Psychiatrische Kliniken Basel | www.upkbs.ch |
n= 198 antipsychotic-naive high risk (HR) n= 206 antipsychotic-naive first-episode psychosis (FEP) n=254 controls
• GM reductions in the temporal, limbic prefrontal cortex within the HR group and in the temporal insular cortex and cerebellum within the FEP group.
• Psychosis onset: GM decreases in temporal, anterior cingulate, cerebellar, and insular regions.
• GM alterations in the temporal regions directly related to severity of psychotic symptoms.
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BOLD effect
| 19 Universitäre Psychiatrische Kliniken Basel | www.upkbs.ch |
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| 20 Universitäre Psychiatrische Kliniken Basel | www.upkbs.ch |
HR: reduced activation in the left inferior frontal gyrus, bilateral medial and superior frontal gyrus and the left anterior cingulate
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| 21 Universitäre Psychiatrische Kliniken Basel | www.upkbs.ch |
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Brain connectivity abnormalities predating the onset of psychosis
| 22 Universitäre Psychiatrische Kliniken Basel | www.upkbs.ch |
Schmidt, A, Smieskova R, Aston, J, Simon A, Allen P, Fusar-Poli P, McGuire PK, Riecher-Rössler A, Stephan KE, Borgwardt SJ (2013) Brain connectivity abnormalities predating the onset of psychosis: correlation with the effect of medication. Archives of General Psychiatry/JAMA Psychiatry, in press.
Regional brain activation during working memory (2-back>0-back). A, Healthy controls. B, Subjects with an at-risk mental state (ARMS). C, Patients experiencing a first-episode psychosis (FEP)
Middle frontal gyrus -> superior parietal lobule connectivity across HC, ARMS and FEP who received antipsychotics (medicated) or not (non-medicated) Abnormalities in Working Memory-induced modulation of connectivity may separate healthy controls from people with an at-risk mental state and patients with first-episode psychosis
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Brain connectivity abnormalities: effect of antipsychotics
| 23 Universitäre Psychiatrische Kliniken Basel | www.upkbs.ch |
Schmidt, A, Smieskova R, Aston, J, Simon A, Allen P, Fusar-Poli P, McGuire PK, Riecher-Rössler A, Stephan KE, Borgwardt SJ (2013) Brain connectivity abnormalities predating the onset of psychosis: correlation with the effect of medication. Archives of General Psychiatry/JAMA Psychiatry, 2013, in press.
• Abnormalities in WM-induced modulation of connectivity may separate healthy controls from people with an at-risk mental state and patients with first-episode psychosis
• Quantitative connectivity may
infer the effects of antipsychotics and benefit the prediction of psychosis
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Integration of structural and functional brain abnormalities
| 24 Universitäre Psychiatrische Kliniken Basel | www.upkbs.ch |
• Vulnerability to psychosis was associated with structural and neurofunctional alterations in fronto-temporo-parietal networks
• Neurofunctional differences were related to a higher risk for transition to psychosis, and thus may be related to different transition probabilities
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| 25 Universitäre Psychiatrische Kliniken Basel | www.upkbs.ch |
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Third generation and translational imaging
› Moves away from simple investigations of the neurobiology underlying
the early phases of schizophrenia
› Translate imaging findings in the clinical field targeting longitudinal
outcomes including transition, remission and response to preventative
interventions
› More complex techniques including diagnostic methods (e.g. support
vector machines)
| 26 Universitäre Psychiatrische Kliniken Basel | www.upkbs.ch |
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Pattern recognition tools for individualized neuroimaging
| 27 Universitäre Psychiatrische Kliniken Basel | www.upkbs.ch |
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Individual prediction of early psychosis
| 28 Universitäre Psychiatrische Kliniken Basel | www.upkbs.ch |
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Summary
› Bilateral prefrontal, limbic and temporo-parietal cortex reductions are
neuroanatomical correlates of an increased vulnerability to psychosis.
› High risk subjects who later become psychotic show additional volumetric
reductions in superior temporal and inferior frontal areas relative to those
who do not.
› Changes in these areas may be crucial to the development of psychotic
illness.
› Functional and structural abnormalities in the high risk group may share a
common pathophysiology
› Prediction on outcomes at single-subject level might be a promising tool to
translate imaging findings as clinical tool
| 29 Universitäre Psychiatrische Kliniken Basel | www.upkbs.ch |
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The work presented here has been done by...
| 30
Department of Psychiatry,
Basel, Switzerland
Institute of Psychiatry
King‘s College London, UK
Universitäre Psychiatrische Kliniken Basel | www.upkbs.ch |
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Many thanks to the patients and volunteers and ...
| 31 Universitäre Psychiatrische Kliniken Basel | www.upkbs.ch |
Section of Neuropsychiatry and Brain Imaging Renata Smieskova, Anna Walter, Fabienne Harrisberger,
Niklaus Denier, Michel Röthlisberger, Johannes Wrege, Early Detection Centre (FEPSY) Anita Riecher-Rössler, Jacqueline Aston, Charlotte Rapp,
Erich Studerus, Hilal Bugra Medical Image Analysis Centre (MIAC) Ernst-Wilhelm Radue, Kerstin Bendfeldt, Stefan Traud,
Pascal Kuster Department of Psychiatry Marc Walter, Gerhard Wiesbeck, Rolf-Dieter Stieglitz,
Klaus Schmeck Department of Neurology Ludwig Kappos, Till Sprenger, Yvonne Naegelin Department of Neuroradiology/Radiological Physics Klaus Scheffler, Christoph Stippich, Claudia Lenz,
Markus Klarhoefer
Institute of Psychiatry, King’s College London
Philip McGuire, Robin Murray,
Paolo Fusar-Poli, Oliver Howes,
Andrea Mechelli, Chris Chaddock,
Marco Picchioni, Sagnik Bhattacharyya,
Paul Allen, Lucia Valmaggia,
Richard Kanaan, Isabel Valli,
Matthew Kempton, OASIS-Team
Department of Neuroradiology, University
of Geneva Sven Haller Department of Psychiatry, University of
Munich Nikos Koutsouleris, Eva Meisenzahl Department of Psychiatry, University of
Bonn Ulrich Ettinger
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If you don’t know what to do next ...
| 32 Universitäre Psychiatrische Kliniken Basel | www.upkbs.ch |
www.neuropsychiatry.ch
www.researchgate.net/profile/Stefan_Borgwardt/
E-mail: [email protected]
Perspectives researchers and clinicians on the interaction of environmental with genetic and neurodevelopmental factors before the onset of psychosis