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Predicting treatment resistance in first episode schizophrenia

Projectomschrijving

De juiste behandeling voorspellen bij schizofrenie

Bij 20-35% van de patiënten met schizofrenie helpen antipsychotica niet. Zij zijn therapie resistent. Dit is voor hen een groot probleem. De onderzoekers gaan testen of een nieuw type MRI scan en bloedbepaling kunnen voorspellen welke patiënten therapie resistent zijn, zodat zij sneller met de juiste medicijnen kunnen worden behandeld.

Producten

Titel: Reliability and Reproducibility of Neuromelanin-Sensitive Imaging of the Substantia Nigra: A Comparison of Three Different Sequences
Auteur: van der Pluijm M, Cassidy C, Zandstra M, Wallert E, de Bruin K, Booij J, de Haan L, Horga G, van de Giessen E
Magazine: Journal of Magnetic Resonance Imaging
Titel: Shortening Duration of Treatment Resistance: The Next Step in the Treatment of Schizophrenia
Auteur: Arjen L Sutterland, Marieke van der Pluijm, Hiske E Becker, Elsmarieke van de Giessen, Lieuwe de Haan
Magazine: Schizophrenia Bulletin
Titel: Plasma dopa decarboxylase activity in treatment-resistant recent-onset psychosis patients
Auteur: van der Pluijm M, Sutterland AL, van Kuilenburg ABP, Zoetekouw L, de Haan L, Booij J, van de Giessen E
Magazine: Therapeutic Advances in Psychopharmacology

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Samenvatting van de aanvraag

Treatment resistance (TR) in schizophrenia is a major clinical problem with 20-35% of psychotic patients showing non-response to antipsychotic treatment. This leads to months to years of delay in effective treatment, resulting in hospitalization and unnecessary side effects of ineffective antipsychotics. We need a biomarker that could be used to switch TR patients at an early stage to clozapine, the only antipsychotic with recognized superior effectiveness in TR. A well-established finding in schizophrenia, using [18F]F-DOPA positron emission tomography (PET) imaging, is increased striatal dopamine synthesis, but interestingly TR patients don’t show altered synthesis. PET imaging however is too costly and invasive to use for TR screening. A novel neuromelanin-sensitive MRI sequence (nMRI), which indirectly measures striatal dopamine synthesis, and which I first used when at Columbia University, has great potential as biomarker for TR. nMRI indeed shows increased signal in schizophrenia patients, but has not yet been tested in TR. Another potential biomarker is a recently developed plasma measure of dopa decarboxylase (DDC) activity, an enzyme required for dopamine synthesis. Furthermore, the role of other neurotransmitters than dopamine in TR is underexposed, of which glutamate is a likely candidate. I will determine whether the novel nMRI sequence and/or plasma DDC activity measure are suitable biomarkers for TR in schizophrenia and explore the role of glutamate as potential biomarker. Therefore, I will acquire nMRI scans, plasma samples for DDC activity and glutamate magnetic resonance spectroscopy (MRS) in 100 first episode psychosis patients and follow them for 6 months to assess TR. I will also acquire [18F]F-DOPA PET scans in a subgroup of patients. If nMRI, plasma DDC activity and possibly glutamate MRS are good biomarkers for TR, I want to develop these as clinical tools in the future, in order to provide appropriate treatment for TR patients at an early stage.

Onderwerpen

Kenmerken

Projectnummer:
91618075
Looptijd: 100%
Looptijd: 100 %
2018
2023
Gerelateerde subsidieronde:
Projectleider en penvoerder:
Dr. E.M. van de Giessen MD PhD
Verantwoordelijke organisatie:
Amsterdam UMC - locatie AMC