title: Striatal D(2/3) Binding Potential Values in Drug-Naïve First-Episode Schizophrenia Patients Correlate With Treatment Outcome.
abstract: One of best validated findings in schizophrenia research is the association between blockade of dopamine D2 receptors and the effects of antipsychotics on positive psychotic symptoms. The aim of the present study was to examine correlations between baseline striatal D(2/3) receptor binding potential (BP(p)) values and treatment outcome in a cohort of antipsychotic-naïve first-episode schizophrenia patients. Additionally, we wished to investigate associations between striatal dopamine D(2/3) receptor blockade and alterations of negative symptoms as well as functioning and subjective well-being. Twenty-eight antipsychotic-naïve schizophrenia patients and 26 controls were included in the study. Single-photon emission computed tomography (SPECT) with [(123)I]iodobenzamide ([(123)I]-IBZM) was used to examine striatal D(2/3) receptor BP(p). Patients were examined before and after 6 weeks of treatment with the D(2/3) receptor antagonist amisulpride. There was a significant negative correlation between striatal D(2/3) receptor BP(p) at baseline and improvement of positive symptoms in the total group of patients. Comparing patients responding to treatment to nonresponders further showed significantly lower baseline BP(p) in the responders. At follow-up, the patients demonstrated a negative correlation between the blockade and functioning, whereas no associations between blockade and negative symptoms or subjective well-being were observed. The results show an association between striatal BP(p) of dopamine D(2/3) receptors in antipsychotic-naïve first-episode patients with schizophrenia and treatment response. Patients with a low BP(p) have a better treatment response than patients with a high BP(p). The results further suggest that functioning may decline at high levels of dopamine receptor blockade.
authors.affiliation: Center for Neuropsychiatric Schizophrenia Research (CNSR) and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Psychiatric Center Glostrup, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences University of Copenhagen, Denmark; sanne@cnsr.dk.
authors.forename: Sanne
authors.initials: S
authors.lastname: Wulff
authors.affiliation: Neurobiology Research Unit (NRU), Rigshospitalet, University of Copenhagen, Denmark;
authors.forename: Lars Hageman
authors.initials: LH
authors.lastname: Pinborg
authors.affiliation: Neurobiology Research Unit (NRU), Rigshospitalet, University of Copenhagen, Denmark;
authors.forename: Claus
authors.initials: C
authors.lastname: Svarer
authors.affiliation: Department of Clinical Physiology and Nuclear Medicine, Herlev Hospital, University of Copenhagen, Denmark;
authors.forename: Lars Thorbjørn
authors.initials: LT
authors.lastname: Jensen
authors.affiliation: Center for Neuropsychiatric Schizophrenia Research (CNSR) and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Psychiatric Center Glostrup, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Mette Ødegaard
authors.initials: MØ
authors.lastname: Nielsen
authors.affiliation: Department of Education, Centre for Research in Compulsory Schooling, Aarhus University, Denmark;
authors.forename: Peter
authors.initials: P
authors.lastname: Allerup
authors.affiliation: Center for Neuropsychiatric Schizophrenia Research (CNSR) and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Psychiatric Center Glostrup, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Nikolaj
authors.initials: N
authors.lastname: Bak
authors.affiliation: Center for Neuropsychiatric Schizophrenia Research (CNSR) and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Psychiatric Center Glostrup, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Hans
authors.initials: H
authors.lastname: Rasmussen
authors.affiliation: Department of Diagnostics, Functional Imaging Unit and Section of Clinical Physiology and Nuclear Medicine, Glostrup Hospital, University of Copenhagen, Denmark.
authors.forename: Erik
authors.initials: E
authors.lastname: Frandsen
authors.affiliation: Department of Diagnostics, Functional Imaging Unit and Section of Clinical Physiology and Nuclear Medicine, Glostrup Hospital, University of Copenhagen, Denmark.
authors.forename: Egill
authors.initials: E
authors.lastname: Rostrup
authors.affiliation: Center for Neuropsychiatric Schizophrenia Research (CNSR) and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Psychiatric Center Glostrup, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences University of Copenhagen, Denmark;
authors.forename: Birte Yding
authors.initials: BY
authors.lastname: Glenthøj
mesh_terms: D000293:Adolescent; D000328:Adult; D000077582:Amisulpride; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012559:Schizophrenia / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D013469:Sulpiride / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013469:Sulpiride; D000077582:Amisulpride
keywords: SPECT; [123I]iodobenzamide; amisulpride; occupancy; subjective well-being