Objectives: To determine whether there are alterations in cytoarchitecture, neuron and interneuron density, and GABA and serotonin receptor subtypes in the PCC and FFG in adult post-mortem autism and control brains.
Methods: Thionin stained sections were used to analyze the cytoarchitecture of the PCC and FFG and immunohistochemistry to identify parvalbumin and calbindin positive GABAergic interneurons. Unbiased, design-based stereological principles were implemented to quantitatively assess the density of thionin, parvalbumin, and calbindin neurons. Receptor binding autoradiography was used to determine the density of GABAergic (GABAA, GABAB, benzodiazepine) and serotonergic (5HT1A, 5HT2A) receptors and transporters (uptake sites; 5HTU).
Results: Cytoarchitectonic abnormalities were observed in the PCC but not in the FFG in the autism cases. The PCC had a poorly defined layer IV, displaced layer V neurons, and increased neurons in the white matter. There was no significant difference in the density of thionin-positive neurons or calbindin- and parvalbumin-positive interneurons in either region. Significant reductions in the density of GABAA and GABAB receptors, benzodiazepine binding sites, 5HT1A and 5HT2A receptors, and 5HTU were observed throughout the PCC and FFG.
Conclusions: The presence of cytoarchitectonic abnormalities in the PCC provides further support for the occurrence of developmental abnormalities within the limbic lobe in the brain in autism. The reduced density of GABAergic and serotonergic receptors does not appear to be the result of a reduced density of neurons within the PCC or FFG, but could be the result of reduced receptors on dendrites or cell bodies or alterations in genes encoding GABA and serotonin receptors. These receptor changes could result in altered synaptic transmission contributing to altered intrinsic and/or extrinsic circuitry with resultant altered processing of emotions and faces, and abnormal social behaviors.