title: The relationship between antipsychotic D2 occupancy and change in frontal metabolism and working memory : A dual [(11)C]raclopride and [(18) F]FDG imaging study with aripiprazole.
abstract: BACKGROUND
  The effects of aripiprazole on cognitive function are obscure, possibly due to the difficulty in disentangling the specific effects on cognitive function from effects secondary to the improvement of other schizophrenic symptoms. This prompts the necessity of using an intermediate biomarker relating the drug effect on the brain to change in cognitive function.
  
  
  OBJECTIVE
  To explore the effect of aripiprazole on cognitive function, we measured changes in frontal metabolism as an intermediate biomarker and sought to determine its relationship with D2 receptor occupancy and changes in working memory.
  
  
  METHODS
  Fifteen healthy male volunteers participated in the study. Serial positron emission tomography (PET) scans with [(11)C]raclopride and [(18) F]FDG were conducted 1 day before and 2 days after the administration of aripiprazole. The subjects performed the N-back task just after finishing the [(18) F]FDG scan.
  
  
  RESULTS
  The mean (±SD) D2 receptor occupancies were 22.2 ± 16.0 % in the 2 mg group, 35.5 ± 3.6 % in the 5 mg group, 63.2 ± 9.9 % in the 10 mg group and 72.8 ± 2.1 % in the 30 mg group. The frontal metabolism was significantly decreased after the administration of aripiprazole (t = 2.705, df = 14, p = 0.017). Greater striatal D2 receptor occupancy was related to greater decrease in frontal metabolism (r = -0.659, p = 0.010), and greater reduction in frontal metabolism was associated with longer reaction times (r = -0.597, p = 0.019) under the greatest task load.
  
  
  CONCLUSIONS
  Aripiprazole can affect cognitive function and alter frontal metabolic function. The changes in these functions are linked to greater D2 receptor occupancy. This suggests that it may be important to find the lowest effective dose of aripiprazole in order to prevent adverse cognitive effects.
authors.affiliation: Department of Psychiatry, Seoul National University College of Medicine, 28 Yeongon-dong, Chongno-gu, Seoul, 110-744, South Korea.
authors.forename: Euitae
authors.initials: E
authors.lastname: Kim
authors.forename: Oliver D
authors.initials: OD
authors.lastname: Howes
authors.forename: Federico E
authors.initials: FE
authors.lastname: Turkheimer
authors.forename: Bo-Hyung
authors.initials: BH
authors.lastname: Kim
authors.forename: Jae Min
authors.initials: JM
authors.lastname: Jeong
authors.forename: Ji Who
authors.initials: JW
authors.lastname: Kim
authors.forename: Jae Sung
authors.initials: JS
authors.lastname: Lee
authors.forename: In-Jin
authors.initials: IJ
authors.lastname: Jang
authors.forename: Sang-Goo
authors.initials: SG
authors.lastname: Shin
authors.forename: Shitij
authors.initials: S
authors.lastname: Kapur
authors.forename: Jun Soo
authors.initials: JS
authors.lastname: Kwon
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000378:metabolism / Q000494:pharmacology*; D000068180:Aripiprazole; D002250:Carbon Radioisotopes; D003071:Cognition / Q000187:drug effects; D003342:Corpus Striatum / Q000378:metabolism; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D005625:Frontal Lobe / Q000378:metabolism; D006801:Humans; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects*; D010879:Piperazines / Q000378:metabolism / Q000494:pharmacology*; D049268:Positron-Emission Tomography / Q000379:methods; D015363:Quinolones / Q000378:metabolism / Q000494:pharmacology*; D020891:Raclopride / Q000378:metabolism; D011930:Reaction Time; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D016037:Single-Blind Method; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D002250:Carbon Radioisotopes; D010879:Piperazines; D015363:Quinolones; D017448:Receptors, Dopamine D2; D019788:Fluorodeoxyglucose F18; D020891:Raclopride; D000068180:Aripiprazole