title: Positron Emission Tomography (PET) Quantification of GABAA Receptors in the Brain of Fragile X Patients.
abstract: Over the last several years, evidence has accumulated that the GABAA receptor is compromised in animal models for fragile X syndrome (FXS), a common hereditary form of intellectual disability. In mouse and fly models, agonists of the GABAA receptor were able to rescue specific consequences of the fragile X mutation. Here, we imaged and quantified GABAA receptors in vivo in brain of fragile X patients using Positron Emission Topography (PET) and [11C]flumazenil, a known high-affinity and specific ligand for the benzodiazepine site of GABAA receptors. We measured regional GABAA receptor availability in 10 fragile X patients and 10 control subjects. We found a significant reduction of on average 10% in GABAA receptor binding potential throughout the brain in fragile X patients. In the thalamus, the brain region showing the largest difference, the GABAA receptor availability was even reduced with 17%. This is one of the first reports of a PET study of human fragile X brain and directly demonstrates that the GABAA receptor availability is reduced in fragile X patients. The study reinforces previous hypotheses that the GABAA receptor is a potential target for rational pharmacological treatment of fragile X syndrome.
authors.affiliation: Department of Medical Genetics, Antwerp University, Antwerp, Belgium.
authors.forename: Charlotte
authors.initials: C
authors.lastname: D'Hulst
authors.affiliation: Department of Medical Genetics, Antwerp University, Antwerp, Belgium.
authors.forename: Inge
authors.initials: I
authors.lastname: Heulens
authors.affiliation: Department of Medical Genetics, Antwerp University, Antwerp, Belgium; Department of Medical Genetics, University Hospital Antwerp, Antwerp, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Van der Aa
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Karolien
authors.initials: K
authors.lastname: Goffin
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Michel
authors.initials: M
authors.lastname: Koole
authors.affiliation: Department of Neuropsychology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Porke
authors.affiliation: Department of Anaesthesiology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Van De Velde
authors.affiliation: Department of Medical Genetics, Antwerp University, Antwerp, Belgium.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Rooms
authors.affiliation: Department of Neurology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Van Paesschen
authors.affiliation: Center for Human Genetics, University Hospitals, Leuven and KULeuven, Leuven, Belgium.
authors.forename: Hilde
authors.initials: H
authors.lastname: Van Esch
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Van Laere
authors.affiliation: Department of Medical Genetics, Antwerp University, Antwerp, Belgium.
authors.forename: R Frank
authors.initials: RF
authors.lastname: Kooy
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D005442:Flumazenil / Q000008:administration & dosage*; D005600:Fragile X Syndrome / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D049268:Positron-Emission Tomography; D011859:Radiography; D011963:Receptors, GABA-A / Q000378:metabolism*
chemical_list: D011963:Receptors, GABA-A; D005442:Flumazenil