The aim of the present study is to detect changes in the dopamine system in the brain of patients with schizophrenia, especially when pretreated with antipsychotic medication. Here, the investigators want to find out whether the treatment with these drugs can cause permanent changes in docking points (receptors) of dopamine in the brain. It will be examined whether number and response of dopamine receptors is altered, which are associated with the onset of psychotic symptoms. For this purpose, a single PET/MR measurement will be performed in all participants. In total 140 volunteers, consisting of 30 healthy volunteers, 20 first-episode, drug-naive patients with schizophrenia and 90 pretreated patients with schizophrenia will be included over a time period of three years. In addition, the influence of nicotine consumption on dopamine receptors will be invesitgated by comparing data from smoking and non-smoking patients. In clinical practice, an elevation of dopamine action caused by alterations in receptors in the brain is of most importance. This may be the reason why the treatment with antipsychotic agents does not work in some patients. In addition, a permanent elevation of dopamine action is associated with permanent brain alterations by these drugs. The result can contribute to work out valuable indications, whether it makes sense to continue a long term therapy with antipsychotic drugs in a patient. But also the in-depth understanding of the impact of nicotine on the course of therapy can help to open up possibilities for improved drug treatment.
This project will study for the first time in humans, whether long-term treatment with antipsychotic agents, representing nowadays gold standard for patients with schizophrenia, may lead to an up regulation of dopamine D2-like receptors and associated, a supersensitivity of these receptors. The detection of such changes and the study of influencing factors (in particular smoking and type of medication) are most important for the understanding of relapse risks, development of treatment resistance and the risks for motor complications of antipsychotic pharmacotherapy. This monocentric, controlled study will include 140 participants over a time period of three years. 30 healthy volunteers, 20 first-episode, drug-naive patients with schizophrenia and 90 pretreated patients with schizophrenia will undergo a single PET/MR measurement.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
140
A single PET/MR-measurement using \[18F\]Fallypride with a duration of 180min. Within this measurement, the dopamine receptor agonist apomorphine is applicated.
Central Institute of Mental Health
Mannheim, Baden-Wurttemberg, Germany
Dopamine D2/D3-receptor availability
Dopamine D2/D3-receptor availability measured as binding potential (BP) using PET and blood-oxygen-level-dependant (BOLD)-response measured with fMRI.
Time frame: 160 minutes
D2/D3-receptor availability in first-episode, drug-naive patients with schizophrenia
In first-episode, drug-naive patients with schizophrenia expressions of NSS and AIMS correlate significantly with striatal D2/D3-receptor availability.
Time frame: 160 minutes
D2/D3-receptor availability in patients with TD
In pretreated, chronically ill patients with schizophrenia, patients with TD show a significantly higher D2/D3-receptor availability than patients without TD.
Time frame: 160 minutes
Follow-up of pretreated, chronically ill patients with schizophrenia
In pretreated, chronically ill patients with schizophrenia, the D2/D3-receptor availability correlates with the relapse risk and the risk for the development of TD over the course of two years.
Time frame: two years
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