Decreased GABA(B) Receptors in the Cingulate Cortex and Fusiform Gyrus in Autism

Department of Anatomy and Neurobiology, Laboratory of Autism Neuroscience Research, Boston University School of Medicine, Boston, MA 02118, USA.
Journal of Neurochemistry (Impact Factor: 4.28). 09/2010; 114(5):1414-23. DOI: 10.1111/j.1471-4159.2010.06858.x
Source: PubMed


J. Neurochem. (2010) 114, 1414–1423.
Autism is a behaviorally defined neurodevelopmental disorder and among its symptoms are disturbances in face and emotional processing. Emerging evidence demonstrates abnormalities in the GABAergic (gamma-aminobutyric acid) system in autism, which likely contributes to these deficits. GABAB receptors play an important role in modulating synapses and maintaining the balance of excitation-inhibition in the brain. The density of GABAB receptors in subjects with autism and matched controls was quantified in the anterior and posterior cingulate cortex, important for socio-emotional and cognitive processing, and the fusiform gyrus, important for identification of faces and facial expressions. Significant reductions in GABAB receptor density were demonstrated in all three regions examined suggesting that alterations in this key inhibitory receptor subtype may contribute to the functional deficits in individuals with autism. Interestingly, the presence of seizure in a subset of autism cases did not have a significant effect on the density of GABAB receptors in any of the three regions.

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    • "Six control ROIs (three anatomical and three functional) were additionally selected based on structures and functions that have been implicated in ASC, but not associated with atypical lateralization. Anatomical ROIs comprised: the anterior cingulate cortex (ACC) [Amaral et al., 2008; Dichter et al., 2009; Oblak et al., 2010; Thakkar et al., 2008], the caudate [Amaral et al., 2008; Langen et al., 2007; Sears et al., 1999], and the fusiform gyrus (FFG) [Amaral et al., 2008; Kwon et al., 2004; Oblak et al., 2010; van Kooten et al., 2008]. Functional ROIs were based on the neurosynth search terms " emotion regulation " (161 studies; k 5 404 voxels) [Mazefsky et al., 2013; Samson et al., 2012], " mentalizing " (124 studies; k 5 1,866 voxels) [Baron-Cohen, 1995; Frith, 2001], and " sensory " (949 studies; k 5 725 voxels) [Leekam et al., 2007; Marco et al., 2011; Tomchek and Dunn, 2007]. "
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    • "Reduced d 3H-muscimol-labeled GABA A receptor binding sites have also been observed in A the posterior cingulate cortex and fusiform gyrus (Oblak et al. 2011 ). Finally, 3 H- CGP54626-labeled GABA B receptor binding sites have also been observed to be reduced in the anterior and posterior cingulate cortex and fusiform gyrus of subjects with autism (Oblak et al. 2010 ). Consistent with the results of binding assays, GABA A and GABA A B receptor subunit proteins have been shown to be reduced in brains of subjects with autism (Fatemi et al. 2009a , b , 2010a , 2014 ). "
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    • "Additionally reduced 3 H-muscimol-labeled GABA A receptor binding sites have been observed in the posterior cingulate cortex and fusiform gyrus of subjects with autism (Oblak et al., 2011). Finally, reduced GABA B receptor binding sites, as measured using 3 H-CGP54626-labeling, have also been identified in the posterior cingulate cortex and fusiform gyrus of subjects with autism (Oblak et al., 2010). Taken together, these studies have demonstrated widespread changes in GABA binding sites in the brains of subjects with schizophrenia and autism. "
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