The brain GABA-benzodiazepine receptor alpha-5 subtype in autism spectrum disorder: A pilot [11C]Ro15-4513 positron emission tomography study

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 [11C]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 [11C]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’.

► It has been proposed that autism spectrum disorder (ASD) is associated with deficient GABA signalling.
► Using [11C]Ro15-4513 PET we measured brain GABAA receptors in adults with ASD.
► [11C]Ro15-4513 binding was reduced throughout the brain of 3 adult males with ASD compared with controls.
► Further analysis showed that results were driven by lower levels of the GABAA α5 subtype.
► These preliminary results provide initial evidence of a GABAA α5 deficit in ASD.