Reduced binding potential of GABA-A/benzodiazepine receptors in individuals at ultra-high risk for psychosis: an [18F]-fluoroflumazenil positron emission tomography study

Schizophr Bull. 2014 May;40(3):548-57. doi: 10.1093/schbul/sbt052. Epub 2013 Apr 15.

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.

Keywords: GABA; PET; caudate; fluoroflumazenil; risk for psychosis; schizophrenia; ultra-high.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Case-Control Studies
  • Caudate Nucleus / diagnostic imaging
  • Caudate Nucleus / metabolism
  • Female
  • Flumazenil / analogs & derivatives*
  • Flumazenil / metabolism
  • Hippocampus / diagnostic imaging
  • Hippocampus / metabolism
  • Humans
  • Male
  • Nucleus Accumbens / diagnostic imaging
  • Nucleus Accumbens / metabolism
  • Parahippocampal Gyrus / diagnostic imaging
  • Parahippocampal Gyrus / metabolism
  • Positron-Emission Tomography
  • Prodromal Symptoms*
  • Protein Binding
  • Putamen / diagnostic imaging
  • Putamen / metabolism
  • Receptors, GABA-A / metabolism*
  • Risk
  • Schizophrenia / diagnostic imaging
  • Schizophrenia / metabolism*
  • Young Adult
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • 2'-fluoroflumazenil
  • Receptors, GABA-A
  • Flumazenil
  • gamma-Aminobutyric Acid