TY - JOUR
T1 - GABAB receptor modulation of visual sensory processing in adults with and without autism spectrum disorder
AU - Huang, Qiyun
AU - Pereira, Andreia C.
AU - Velthuis, Hester
AU - Wong, Nichol
AU - Ellis, Claire
AU - Ponteduro, Francesca
AU - Dimitrov, Mihail
AU - Kowalewski, Lukasz
AU - Lythgoe, David
AU - Rotaru, Diana
AU - Edden, Richard
AU - Leonard, Alison
AU - Ivin, Glynis
AU - Ahmad, Jumana
AU - Pretzsch, Charlotte
AU - Daly, Eileen
AU - Murphy, Declan
AU - McAlonan, Grainne
PY - 2022/1/5
Y1 - 2022/1/5
N2 - Sensory atypicalities in autism spectrum disorder (ASD) are thought to arise at least partly from differences in γ-aminobutyric acid (GABA) receptor function. However, the evidence to date has been indirect, arising from correlational studies in patients and preclinical models. Here, we evaluated the role of GABA receptor directly, in 44 adults (n = 19 ASD). Baseline concentration of occipital lobe GABA+ (GABA plus coedited macromolecules) was measured using proton magnetic resonance spectroscopy (1H-MRS). Steady-state visual evoked potential (SSVEP) elicited by a passive visual surround suppression paradigm was compared after double-blind randomized oral administration of placebo or 15 to 30 mg of arbaclofen (STX209), a GABA type B (GABAB) receptor agonist. In the placebo condition, the neurotypical SSVEP response was affected by both the foreground stimuli contrast and background interference (suppression). In ASD, however, all stimuli conditions had equal salience and background suppression of the foreground response was weaker. In the placebo condition, although there was no difference in GABA+ between groups, GABA+ concentration positively correlated with response to maximum foreground contrast during maximum background interference in neurotypicals, but not ASD. In neurotypicals, sensitivity to visual stimuli was disrupted by 30 mg of arbaclofen, whereas in ASD, it was made more “typical” and visual processing differences were abolished. Hence, differences in GABAergic function are fundamental to autistic (visual) sensory neurobiology and are modulated by GABAB activity.
AB - Sensory atypicalities in autism spectrum disorder (ASD) are thought to arise at least partly from differences in γ-aminobutyric acid (GABA) receptor function. However, the evidence to date has been indirect, arising from correlational studies in patients and preclinical models. Here, we evaluated the role of GABA receptor directly, in 44 adults (n = 19 ASD). Baseline concentration of occipital lobe GABA+ (GABA plus coedited macromolecules) was measured using proton magnetic resonance spectroscopy (1H-MRS). Steady-state visual evoked potential (SSVEP) elicited by a passive visual surround suppression paradigm was compared after double-blind randomized oral administration of placebo or 15 to 30 mg of arbaclofen (STX209), a GABA type B (GABAB) receptor agonist. In the placebo condition, the neurotypical SSVEP response was affected by both the foreground stimuli contrast and background interference (suppression). In ASD, however, all stimuli conditions had equal salience and background suppression of the foreground response was weaker. In the placebo condition, although there was no difference in GABA+ between groups, GABA+ concentration positively correlated with response to maximum foreground contrast during maximum background interference in neurotypicals, but not ASD. In neurotypicals, sensitivity to visual stimuli was disrupted by 30 mg of arbaclofen, whereas in ASD, it was made more “typical” and visual processing differences were abolished. Hence, differences in GABAergic function are fundamental to autistic (visual) sensory neurobiology and are modulated by GABAB activity.
UR - http://www.scopus.com/inward/record.url?scp=85123229092&partnerID=8YFLogxK
U2 - 10.1126/scitranslmed.abg7859
DO - 10.1126/scitranslmed.abg7859
M3 - Article
C2 - 34985973
AN - SCOPUS:85123229092
SN - 1946-6234
VL - 14
SP - eabg7859
JO - Science Translational Medicine
JF - Science Translational Medicine
IS - 626
M1 - eabg7859
ER -