title: The brain GABA-benzodiazepine receptor alpha-5 subtype in autism spectrum disorder: a pilot [(11)C]Ro15-4513 positron emission tomography study.
abstract: GABA (gamma-amino-butyric-acid) is the primary inhibitory neurotransmitter in the human brain. It has been proposed that the symptoms of autism spectrum disorders (ASDs) are the result of deficient GABA neurotransmission, possibly including reduced expression of GABAA receptors. However, this hypothesis has not been directly tested in living adults with ASD. In this preliminary investigation, we used Positron Emission Tomography (PET) with the benzodiazepine receptor PET ligand [(11)C]Ro15-4513 to measure α1 and α5 subtypes of the GABAA receptor levels in the brain of three adult males with well-characterized high-functioning ASD compared with three healthy matched volunteers. We found significantly lower [(11)C]Ro15-4513 binding throughout the brain of participants with ASD (p < 0.0001) compared with controls. Planned region of interest analyses also revealed significant reductions in two limbic brain regions, namely the amygdala and nucleus accumbens bilaterally. Further analysis suggested that these results were driven by lower levels of the GABAA α5 subtype. These results provide initial evidence of a GABAA α5 deficit in ASD and support further investigations of the GABA system in this disorder. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'.
authors.affiliation: King's College London, Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, PO Box 50, De Crespigny Park, London SE5 8AF, UK.
authors.forename: Maria Andreina
authors.initials: MA
authors.lastname: Mendez
authors.forename: Jamie
authors.initials: J
authors.lastname: Horder
authors.forename: Jim
authors.initials: J
authors.lastname: Myers
authors.forename: Suzanne
authors.initials: S
authors.lastname: Coghlan
authors.forename: Paul
authors.initials: P
authors.lastname: Stokes
authors.forename: David
authors.initials: D
authors.lastname: Erritzoe
authors.forename: Oliver
authors.initials: O
authors.lastname: Howes
authors.forename: Anne
authors.initials: A
authors.lastname: Lingford-Hughes
authors.forename: Declan
authors.initials: D
authors.lastname: Murphy
authors.forename: David
authors.initials: D
authors.lastname: Nutt
mesh_terms: D000328:Adult; D001321:Autistic Disorder / Q000000981:diagnostic imaging / Q000378:metabolism*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D008297:Male; D021122:Protein Subunits / Q000378:metabolism; D011877:Radionuclide Imaging; D011963:Receptors, GABA-A / Q000378:metabolism*
chemical_list: D021122:Protein Subunits; D011963:Receptors, GABA-A