HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

In vivo measurement of GABA transmission in healthy subjects and schizophrenia patients.

AbstractOBJECTIVE:
Postmortem studies in schizophrenia reveal alterations in gene products that regulate the release and extracellular persistence of GABA. However, results of in vivo studies of schizophrenia measuring total tissue GABA with magnetic resonance spectroscopy (MRS) have been inconsistent. Neither the postmortem nor the MRS studies directly address the physiological properties of GABA neurotransmission. The present study addresses this question through an innovative positron emission tomography (PET) paradigm.
METHOD:
The binding of [(11)C]flumazenil, a benzodiazepine-specific PET radiotracer, was measured before and after administration of tiagabine (0.2 mg/kg of body weight), a GABA membrane transporter (GAT1) blocker, in 17 off-medication patients with schizophrenia and 22 healthy comparison subjects. Increased extracellular GABA, through GAT1 blockade, enhances the affinity of GABAA receptors for benzodiazepine ligands, detected as an increase in [(11)C]flumazenil tissue distribution volume (VT).
RESULTS:
[(11)C]Flumazenil VT was significantly increased across all cortical brain regions in the healthy comparison group but not in the schizophrenia group. This lack of effect was most prominent in the antipsychotic-naive schizophrenia group. In this subgroup, [(11)C]flumazenil ΔVT in the medial temporal lobe was correlated with positive symptoms, and baseline [(11)C]flumazenil VT in the medial temporal lobe was negatively correlated with visual learning. In the healthy comparison group but not the schizophrenia group, [(11)C]flumazenil ΔVT was positively associated with gamma-band oscillation power.
CONCLUSIONS:
This study demonstrates, for the first time, an in vivo impairment in GABA transmission in schizophrenia, most prominent in antipsychotic-naive individuals. The impairment in GABA transmission appears to be linked to clinical symptoms, disturbances in cortical oscillations, and cognition.
AuthorsW Gordon Frankle, Raymond Y Cho, Konasale M Prasad, N Scott Mason, Jennifer Paris, Michael L Himes, Christopher Walker, David A Lewis, Rajesh Narendran
JournalThe American journal of psychiatry (Am J Psychiatry) Vol. 172 Issue 11 Pg. 1148-59 (Nov 01 2015) ISSN: 1535-7228 [Electronic] United States
PMID26133962 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Carbon Radioisotopes
  • GABA Modulators
  • GABA Plasma Membrane Transport Proteins
  • Neurotransmitter Uptake Inhibitors
  • Nipecotic Acids
  • SLC6A1 protein, human
  • Flumazenil
  • gamma-Aminobutyric Acid
  • Tiagabine
Topics
  • Adult
  • Carbon Radioisotopes
  • Case-Control Studies
  • Cerebral Cortex (diagnostic imaging, metabolism, physiopathology)
  • Female
  • Flumazenil
  • GABA Modulators
  • GABA Plasma Membrane Transport Proteins
  • Gamma Rhythm
  • Humans
  • Male
  • Neuropsychological Tests
  • Neurotransmitter Uptake Inhibitors
  • Nipecotic Acids
  • Positron-Emission Tomography
  • Schizophrenia (diagnostic imaging, metabolism, physiopathology)
  • Schizophrenic Psychology
  • Synaptic Transmission
  • Temporal Lobe (diagnostic imaging, metabolism, physiopathology)
  • Tiagabine
  • Young Adult
  • gamma-Aminobutyric Acid (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: