DECREASED GABA-B RECEPTOR DENSITY IN THE ANTERIOR AND POSTERIOR CINGULATE CORTICES IN AUTISM

Background: Neuropathology and genetic studies have implicated abnormalities in GABA as a potential substrate for autistic behavior. Prior autoradiographic studies have demonstrated widespread, significant changes in GABA_A receptors. Comparable studies on GABA_B receptors are lacking in the autistic brain. GABA_B receptors are normally distributed throughout the brain both pre- and postsynaptically. Presynaptic GABA_B receptors suppress neurotransmitter release by inhibiting calcium channels. These receptors have been detected at extrasynaptic sites and occasionally at glutamatergic or GABAergic terminals. Postsynaptically, the receptors are found on dendritic shafts and spines of cortical pyramidal neurons and interneurons, respectively. The cingulate cortex has been implicated in mediating socio-emotional behavior, a core deficit in autism.

Objectives: To determine the density and laminar distribution of GABA_B receptors in the anterior (ACC) and posterior cingulate (PCC) cortices in adult autistic and control cases.

Methods: Radioligand binding experiments were completed in the ACC and PCC for GABA_B receptors using ³H-CGP54626 in adult autistic (ACC, n=7; PCC, n=6) and control (ACC, n= 9; PCC, n=7) brains controlled for age and post-mortem interval. Optical densities were measured in the superficial (I-III) and deep (V-VI) layers using the Inquiry program. Student t-tests were used to compare the layers by group.

Results: Overall, there was a significant reduction in the density of GABA_B receptors in the autistic brains in the ACC (p=0.02) and PCC (p=0.008). Specifically, a significant reduction in the density of GABA_B receptors was found in the superficial layers of the ACC (p=0.001) and PCC (p=0.007) without significant difference in the deep layers of either the ACC or PCC.

Conclusions: Decreased density in GABA_B receptors provides additional quantitative evidence for the involvement of the GABA system in the neuropathology of the ACC and PCC in autism and may in part underlie some of the social-emotional behavioral alterations observed in this disorder.