Reduced GABA_A receptors and benzodiazepine binding sites in the posterior cingulate cortex and fusiform gyrus in autism

摘要

Individuals with autism display deficits in the social domain including the proper recognition of faces and interpretations of facial expressions. There is an extensive network of brain regions involved in face processing including the fusiform gyrus (FFG) and posterior cingulate cortex (PCC). Functional imaging studies have found that controls have increased activity in the PCC and FFG during face recognition tasks, and the FFG has differential responsiveness in autism when viewing faces. Multiple lines of evidence have suggested that the GABAergic system is disrupted in the brains of individuals with autism and it is likely that altered inhibition within the network influences the ability to perceive emotional expressions. On-the-slide ligand binding autoradiography was used to determine if there were alterations in GABA_A and/or benzodiazepine binding sites in the brain in autism. Using ~3H-muscimol and ~3H-flunitrazepam we could determine whether the number (B_max), binding affinity (K_d), and/or distribution of GABA_A receptors and benzodiazepine binding sites (BZD) differed from controls in the FFG and PCC. Significant reductions were found in the number of GABA_A receptors and BZD binding sites in the superficial layers of the PCC and FFG, and in the number of BZD binding sites in the deep layers of the FFG. In addition, the autism group had a higher binding affinity in the superficial layers of the GABA_A study. Taken together, these findings suggest that the disruption in inhibitory control in the cortex may contribute to the core disturbances of socio-emotional behaviors in autism.