- TR patients have lower nMRI signal in the substantia nigra than responders. - nMRI signal in the substantia nigra correlates positively with striatal dopamine synthesis on [18F]F-DOPA PET. - TR patients have lower plasma DDC activity than…
ID
Bron
Verkorte titel
Aandoening
Schizophrenia, treatment resistance, psychosis, schizofrenie, therapie resistentie, psychose
Ondersteuning
Onderzoeksproduct en/of interventie
Uitkomstmaten
Primaire uitkomstmaten
- Treatment resistance<br>
- Neuromelanin contrast ratio on nMRI<br>
- Glutamate/Creatine ratio on MRS in ACC<br>
- Plasma DDC activity<br>
- [18F]F-DOPA influx (Ki) value (for subgroup of 40 patients)
Achtergrond van het onderzoek
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 guide the treatment decision 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 this altered synthesis. The gold standard for measuring dopamine 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, 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.
Doel van het onderzoek
- TR patients have lower nMRI signal in the substantia nigra than responders.
- nMRI signal in the substantia nigra correlates positively with striatal dopamine synthesis on [18F]F-DOPA PET.
- TR patients have lower plasma DDC activity than responders.
- Plasma DDC activity correlates positively with striatal dopamine synthesis on [18F]F-DOPA PET.
- TR patients have higher ACC glutamate than responders as measured with magnetic resonance spectroscopy (MRS).
Onderzoeksopzet
Participants will have three visits: one baseline visit and two follow-up visits at 6 weeks and 6 months. A subgroup of 40 patients will have an additional visit for an [18F]F-DOPA PET/CT scan.
Onderzoeksproduct en/of interventie
None
Publiek
Wetenschappelijk
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
- First episode psychosis
- Age 18-35 years old
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
- Antipsychotic use longer than one year
- Dependence on other substances of abuse than nicotine or cannabis
- Use of amphetamine, cocaine or medication for ADHD (attention deficit hyperactivity disorder), since these drugs influence the dopamine system
-Neurological disorder (e.g. epilepsy) or evidence of brain damage
-Inability to provide informed consent
- Contra-indications for MRI (including pacemaker, ferromagnetic implants, claustrophobia)
- Pregnancy
Opzet
Deelname
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Andere (mogelijk minder actuele) registraties in dit register
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In overige registers
| Register | ID |
|---|---|
| NTR-new | NL7231 |
| NTR-old | NTR7430 |
| CCMO | NL63410.018.17 |
| OMON | NL-OMON48828 |