title: Serotonin2A receptor blockade and clinical effect in first-episode schizophrenia patients treated with quetiapine.
abstract: BACKGROUND
  We have previously reported decreased frontal cortical serotonin2A receptor binding in 30 antipsychotic naïve first-episode schizophrenic patients and a relationship between this binding and positive psychotic symptoms. Until now, no longitudinal studies of serotonin2A receptor in first-episode antipsychotic-naïve schizophrenia patients have reported on the relationship between serotonin2A receptor occupancy and treatment effect after sustained treatment with a specific atypical antipsychotic compound.
  
  
  OBJECTIVE
  Here, we measured serotonin2A receptor occupancy with [(18)F]altanserin PET in 15 first-episode antipsychotic-naïve schizophrenia patients before and after 6 months of quetiapine treatment. Moreover, we investigated possible relationships between clinical efficacy, oral dose, and plasma levels of quetiapine
  
  
  RESULTS
  Significant nonlinear relationships were found between serotonin2A receptor occupancy, quetiapine dose, and plasma concentration. There was a modest effect on positive symptoms up until a serotonin2A receptor occupancy level of approximately 60%. A receptor occupancy level between 60% and 70% appeared to exert the optimal serotonin2A receptor related treatment effect on positive symptoms whereas no additional serotonin2A receptor associated treatment effect was obtained above a receptor occupancy of 70%.
  
  
  CONCLUSIONS
  Taken together, the data point to a therapeutic role of the serotonin2A receptor in the treatment of subgroups of patients with schizophrenia. Specifically, the study indicates a serotonin2A receptor associated therapeutic window on positive symptoms in responding patients in the range between 60% and 70% occupancy in antipsychotic-naïve first-episode schizophrenia. We speculate that non-responding patients need higher dopamine D(2) receptor blockade. Future studies with concurrent measurement of interactions with the dopamine system are, however, warranted to clarify this.
authors.affiliation: Center for Neuropsychiatric Schizophrenia Research, Faculty of Health Sciences, Copenhagen University Hospital Glostrup, Copenhagen, Denmark. hans@cnsr.dk
authors.forename: Hans
authors.initials: H
authors.lastname: Rasmussen
authors.forename: Bjorn H
authors.initials: BH
authors.lastname: Ebdrup
authors.forename: David
authors.initials: D
authors.lastname: Erritzoe
authors.forename: Bodil
authors.initials: B
authors.lastname: Aggernaes
authors.forename: Bob
authors.initials: B
authors.lastname: Oranje
authors.forename: Jan
authors.initials: J
authors.lastname: Kalbitzer
authors.forename: Lars H
authors.initials: LH
authors.lastname: Pinborg
authors.forename: William F C
authors.initials: WF
authors.lastname: Baaré
authors.forename: Claus
authors.initials: C
authors.lastname: Svarer
authors.forename: Henrik
authors.initials: H
authors.lastname: Lublin
authors.forename: Gitte M
authors.initials: GM
authors.lastname: Knudsen
authors.forename: Birte
authors.initials: B
authors.lastname: Glenthoj
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D003987:Dibenzothiazepines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007650:Ketanserin / Q000031:analogs & derivatives; D008137:Longitudinal Studies; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods; D000069348:Quetiapine Fumarate; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects* / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D012565:Schizophrenic Psychology; D013997:Time Factors; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D044402:Receptor, Serotonin, 5-HT2A; D000069348:Quetiapine Fumarate; C071983:altanserin; D007650:Ketanserin