Abstract
Predicting treatment response in schizophrenia: the role of striatal and frontal dopamine D2/D3 receptor binding potential
Authors: Henrik Nørbak-Emig, Sanne Wulff, Mette Ø. Nielsen, Hans Rasmussen, Egill Rostrup, Nikolaj Bak, Lars Pinborg, Claus Svarer, Lars Thorbjørn Jensen, Bjørn H. Ebdrup, Birte Y. Glenthøj
Background: One of the best validated findings in schizophrenia is an association between increased presynaptic striatal dopaminergic activity and psychotic symptoms. Preclinical studies suggest an inverse relationship between frontal and striatal dopamine activity. This activity can indirectly be expressed by the binding potential (BP) of dopamine receptors using Single Photon Emission Computed Tomography (SPECT) where low striatal BP is believed to reflect high dopamine availability.
Aim to assess the association between D2 receptor BPs in antipsychotic-naïve first-episode schizophrenia patients and their response to the first treatment with an antipsychotic compound.
Method: We have data from two comparable cohorts of antipsychotic-naïve first-episode schizophrenia patients the IBZMcohort and the EPIcohort. Both cohorts were longitudinal studies. The examinations included structural Magnetic Resonance Imaging, SPECT and PANSS.
In the IBZMcohort we included 26 patients. We used the ligand [123]IBZM (123labeled iodbenzamid) to examine the binding potential (BP) of dopamine D2/D3 receptors in striatum. Patients were treated with amisulpride for six weeks. In the EPIcohort we included 25 patients. The ligand [123I]epidepride was used for quantification of extrastriatal dopamine D2/D3 receptors. Patients were randomised to twelve weeks of treatment with either risperidone or zuclopenthixol.
Results: In the IBZMcohort the mean PANSS total score was 79 at baseline and 65 at follow-up. There was a negative correlation between striatal BP and improvement of the PANSS total score (Rho=-0,553 P=0.009). Furthermore we found a negative correlation between striatal BP and improvement of positive symptoms among the male patients only (P=0.020). The same relationship was found at trend level for the entire group (Rho=-0,417 P=0,060).
In the EPIcohort the mean PANSS total score was 70 at baseline and 48 at follow up. In the frontal cortex we found a positive correlation (Rho=0.56 P=0.003) between BP and change in positive symptom score for the whole group as well as in the subgroup treated with risperidone.
Discussion: Our preliminary results suggest that D2 BP in antipsychotic-naïve patients may serve as a predictor for treatment outcome and further support an inverse relationship between frontal and striatal dopamine activity.
Authors: Henrik Nørbak-Emig, Sanne Wulff, Mette Ø. Nielsen, Hans Rasmussen, Egill Rostrup, Nikolaj Bak, Lars Pinborg, Claus Svarer, Lars Thorbjørn Jensen, Bjørn H. Ebdrup, Birte Y. Glenthøj
Background: One of the best validated findings in schizophrenia is an association between increased presynaptic striatal dopaminergic activity and psychotic symptoms. Preclinical studies suggest an inverse relationship between frontal and striatal dopamine activity. This activity can indirectly be expressed by the binding potential (BP) of dopamine receptors using Single Photon Emission Computed Tomography (SPECT) where low striatal BP is believed to reflect high dopamine availability.
Aim to assess the association between D2 receptor BPs in antipsychotic-naïve first-episode schizophrenia patients and their response to the first treatment with an antipsychotic compound.
Method: We have data from two comparable cohorts of antipsychotic-naïve first-episode schizophrenia patients the IBZMcohort and the EPIcohort. Both cohorts were longitudinal studies. The examinations included structural Magnetic Resonance Imaging, SPECT and PANSS.
In the IBZMcohort we included 26 patients. We used the ligand [123]IBZM (123labeled iodbenzamid) to examine the binding potential (BP) of dopamine D2/D3 receptors in striatum. Patients were treated with amisulpride for six weeks. In the EPIcohort we included 25 patients. The ligand [123I]epidepride was used for quantification of extrastriatal dopamine D2/D3 receptors. Patients were randomised to twelve weeks of treatment with either risperidone or zuclopenthixol.
Results: In the IBZMcohort the mean PANSS total score was 79 at baseline and 65 at follow-up. There was a negative correlation between striatal BP and improvement of the PANSS total score (Rho=-0,553 P=0.009). Furthermore we found a negative correlation between striatal BP and improvement of positive symptoms among the male patients only (P=0.020). The same relationship was found at trend level for the entire group (Rho=-0,417 P=0,060).
In the EPIcohort the mean PANSS total score was 70 at baseline and 48 at follow up. In the frontal cortex we found a positive correlation (Rho=0.56 P=0.003) between BP and change in positive symptom score for the whole group as well as in the subgroup treated with risperidone.
Discussion: Our preliminary results suggest that D2 BP in antipsychotic-naïve patients may serve as a predictor for treatment outcome and further support an inverse relationship between frontal and striatal dopamine activity.
| Original language | English |
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| Publication date | 8 Oct 2014 |
| Number of pages | 1 |
| Publication status | Published - 8 Oct 2014 |
| Event | Forskningsdag 2014, Glostrup Hospital - Glostrup, Denmark Duration: 8 Oct 2014 → 8 Oct 2014 |
Conference
| Conference | Forskningsdag 2014, Glostrup Hospital |
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| Country/Territory | Denmark |
| City | Glostrup |
| Period | 08/10/2014 → 08/10/2014 |