Neuroanatomical and neurochemical alterations in the cingulate cortex and fusiform gyrus in autism.

摘要

Individuals with autism have a pervasive impairment in social interactions that include difficulties in identifying, remembering, and processing facial expressions and emotions. Brain regions involved in emotion, memory, and face processing are the anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and fusiform gyrus (FFG). The ACC plays a role in processing emotions and producing facial expressions that convey emotion, while the PCC is involved in memory and processing emotionally significant experiences. The FFG is known for its role in facial recognition. Previous neuropathology studies in cortical areas in autism suggest abnormal cytoarchitecture with defects in cortical migration and a reduction in neuron density. In addition, a leading theory in autism is that there is an imbalance between excitatory and inhibitory neurotransmission having effects on cortical circuits. Receptors for gamma-amino butyric acid (GABA) and serotonin (5-HT) have emerged as potential substrates for this imbalance. We hypothesize that the autistic group would exhibit neuropathology in the cingulate cortex and fusiform gyrus, a change in the density of neurons, including GABAergic interneurons, and a decrease in GABA receptors, benzodiazepine binding sites, and serotonin receptors. Results revealed no significant differences in neuronal density for neurons identified with thionin or for calbindin- or parvalbumin-immunoreactive interneurons in the PCC or FFG However, there were significant reductions in the densities of GABAA and GABAB receptors, benzodiazepine binding sites, 5HT1A and 5HT2A receptors, and serotonin transporters (5HTT) in the PCC and FFG. Abnormalities in cytoarchitecture were observed in the PCC but not the FFG. These abnormalities included a poorly defined layer IV, displaced layer V neurons, and increased neurons in the white matter. The presence of these cytoarchitectonic abnormalities within the PCC suggests an early developmental abnormality within the PCC. Since there was no overall loss of neurons, the reduced density of GABAergic and serotonergic receptors most likely results from altered synaptic density or alterations in gene expression for specific GABA and serotonin receptor subtypes. The changes in receptor density observed here in the autistic brain would likely alter synaptic transmission impacting cortical circuitry critical for processing emotional and facial information.