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Region Hovedstaden - en del af Københavns Universitetshospital

DOPAMINE D2 RECEPTOR BINDING, BRAIN STRUCTURE AND PSYCHOPATHOLOGY IN ANTIPSYCHOTIC-NAIVE FIRST-EPISODE SCHIZOPHRENIA PATIENTS: ASSOCIATIONS BEFORE AND AFTER ANTIPSYCHOTIC MONOTHERAPY

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Whether progressive changes in brain volume are caused by the illness or by antipsychotic treatment (particularly, the blockade of dopamine D2 (D2) receptors) is one of the key questions in schizophrenia research. The question is best answered by studying antipsychotic-naive first-episode schizophrenia patients before and after their first treatment with a specific antipsychotic compound. In the present new Ph.D. study, we take advantage of the fact that we have access to two comparable cohorts (A and C) of never previously treated first-episode schizophrenia patients, who went through an extensive examination program including structural MRI, SPECT, cognition, and psychopathology before and after antipsychotic monotherapy with 3 different compounds (amisulpride, risperidone, and zuclopenthixol).
Patients in cohort A was randomized to treatment with zuclopenthixol or risperidone, a first, respectively, a second generation antipsychotic compound (FGA, respectively FGA); both with high affinity for the D2 site, but also affinity for other receptor systems as well. The patients in cohort C were all treated with amisulpride, a SGA with a relatively selective affinity for D2 and D3 receptors. For the SPECT examinations in cohort A we used the ligand [123I]epidepride. Epidepride is suitable for examinations of extrastriatal, but not striatal D2/D3 receptors. In contrast to this, we used a ligand suitable for studying striatal D2/D3 receptors, 123IBZM, in cohort C. In this way data from the two cohorts will supplement each other.
Data from cohort A will contribute with new knowledge on associations between D2/D3 receptor binding potentials (BP) in frontal cortex, temporal cortex, and thalamus in the antipsychotic-naive state and the succeeding changes in brain volume, treatment response, and extrapyramidal side-effects (EPS) following antipsychotic treatment/ D2/D3 receptor blockade; in other words, whether D2/D3 receptor BP in drug-naive patients can serve as a biomarker for progressive brain changes and clinical outcome. Additionally, the data will contribute with highly clinically relevant information on the association between extrastriatal D2/D3 receptor blockade and changes in brain structure, treatment outcome, and side effects.
The data from cohort C will complement the data from cohort A by adding information on the same associations before and after antipsychotic monotherapy, but this time in the basal ganglia (BG).
D2/D3 receptor BP (before treatment) and blockade (after treatment) in striatal as well as extrastriatal areas will also be related to outcome with regard to cognitive functions in collaborative studies (not part of the present Ph.D. study).
The combined data from two comparable first-episode cohorts will contribute with unique new knowledge on associations between D2/D3 receptor BP in the cortico-striato-thalamo-cortical circuits in drug-naive patients and succeeding brain changes and treatment outcome; i.e., characterize regional D2/D3 receptor BP as potential biomarkers. They will further add just as important information on the association between D2/D3 receptor blockade after antipsychotic monotherapy and volume changes, treatments effects, side-effects, and cognitive function.
StatusAfsluttet
Periode01/02/201231/12/2015
FinansieringskildeIntern støtte (Offentlig)
ForskningsprogramRegion Hovedstaden Psykiatri
Beløb1.060.000,00 Danske Kroner
Årstal2013

ID: 36377303