title: Reduced binding potential of GABA-A/benzodiazepine receptors in individuals at ultra-high risk for psychosis: an [18F]-fluoroflumazenil positron emission tomography study.
abstract: BACKGROUND
  Altered transmission of gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter, may contribute to the development of schizophrenia. The purpose of the present study was to investigate the presence of GABA-A/benzodiazepine (BZ) receptor binding abnormalities in individuals at ultra-high risk (UHR) for psychosis in comparison with normal controls using [(18)F]-fluoroflumazenil (FFMZ) positron emission tomography (PET). In particular, we set regions of interest in the striatum (caudate, putamen, and nucleus accumbens) and medial temporal area (hippocampus and parahippocampal gyrus).
  
  
  METHODS
  Eleven BZ-naive people at UHR and 15 normal controls underwent PET scanning using [(18)F]-FFMZ to measure GABA-A/BZ receptor binding potential. The regional group differences between UHR individuals and normal controls were analyzed using Statistical Parametric Mapping 8 software. Participants were evaluated using the structured interview for prodromal syndromes and neurocognitive function tasks.
  
  
  RESULTS
  People at UHR demonstrated significantly reduced binding potential of GABA-A/BZ receptors in the right caudate.
  
  
  CONCLUSIONS
  Altered GABAergic transmission and/or the imbalance of inhibitory and excitatory systems in the striatum may be present at the putative prodromal stage and play a pivotal role in the pathophysiology of psychosis.
authors.affiliation: *To whom correspondence should be addressed; Department of Psychiatry, Severance Mental Health Hospital, Yonsei University Health System, 119, 1926 Beon-gil, Gyeongchung-daero, Gwangju-si, Gyeonggi-do 464-100, South Korea; tel: +82-31-760-9404, fax: +82-31-761-7582, e-mail: ansk@yuhs.ac.
authors.forename: Jee In
authors.initials: JI
authors.lastname: Kang
authors.forename: Hae-Jeong
authors.initials: HJ
authors.lastname: Park
authors.forename: Se Joo
authors.initials: SJ
authors.lastname: Kim
authors.forename: Kyung Ran
authors.initials: KR
authors.lastname: Kim
authors.forename: Su Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Eun
authors.initials: E
authors.lastname: Lee
authors.forename: Suk Kyoon
authors.initials: SK
authors.lastname: An
authors.forename: Jun Soo
authors.initials: JS
authors.lastname: Kwon
authors.forename: Jong Doo
authors.initials: JD
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D016022:Case-Control Studies; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D005442:Flumazenil / Q000031:analogs & derivatives* / Q000378:metabolism; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D008297:Male; D009714:Nucleus Accumbens / Q000000981:diagnostic imaging / Q000378:metabolism; D020534:Parahippocampal Gyrus / Q000000981:diagnostic imaging / Q000378:metabolism; D049268:Positron-Emission Tomography; D062706:Prodromal Symptoms; D011485:Protein Binding; D011699:Putamen / Q000000981:diagnostic imaging / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism*; D012306:Risk; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000378:metabolism*; D055815:Young Adult; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: C483765:2'-fluoroflumazenil; D011963:Receptors, GABA-A; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid
keywords: GABA; PET; caudate; fluoroflumazenil; risk for  psychosis; schizophrenia; ultra-high