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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Healthy subjects | Other | 30 healthy subjects will undergo a single PET/MR-measurement. |
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| First-episode, drug-naive patients with schizophrenia | Experimental | 20 first-episode, drug-naive patients with schizophrenia will undergo a single PET/MR-measurement. |
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| Pretreated chronically ill patients with schizophrenia | Experimental | 90 pretreated chronically ill patients with schizophrenia will undergo a single PET/MR-measurement. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Single PET/MR-measurement | Radiation | A single PET/MR-measurement using [18F]Fallypride with a duration of 180min. Within this measurement, the dopamine receptor agonist apomorphine is applicated. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 160 minutes |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 160 minutes |
| D2/D3-receptor availability in patients with TD |
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Inclusion Criteria for healthy subjects:
Inclusion Criteria for patients:
Exclusion criteria for patients and subjects:
Additional exclusion criterion for patients: other than the approved axis I diagnosis according to DSM-5. An axis II diagnosis is not a criterion for exclusion
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| Name | Affiliation | Role |
|---|---|---|
| Gerhard GrĂ¼nder, Prof. Dr. | Central Institute of Mental Health, Mannheim | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Central Institute of Mental Health | Mannheim | Baden-Wurttemberg | 68159 | Germany |
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| ID | Term |
|---|---|
| D012559 | Schizophrenia |
| ID | Term |
|---|---|
| D019967 | Schizophrenia Spectrum and Other Psychotic Disorders |
| D001523 | Mental Disorders |
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All study participants will undergo a single PET/MR-measurement.
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In pretreated, chronically ill patients with schizophrenia, patients with TD show a significantly higher D2/D3-receptor availability than patients without TD. |
| 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. | two years |