GABAergic and Serotonergic Receptor Alterations in the Fusiform Gyrus in Autism

Background: Autism is characterized by the presence of deficits in social interaction, language, and repetitive behaviors.  A key to normal social functioning in humans is face processing, which enables individuals to identify others and understand the mental state of others.  Recent imaging studies looking at the fusiform gyrus (FFG), the key area in face identification and processing, have been contradictory.  Some studies have shown that patients with autism are capable of performing face perception tasks yet others have found the FFG and other cortical regions involved in face processing are hypoactive in individuals with autism.  A recent stereological investigation has shown that there are fewer and smaller neurons in the FFG in autism.  However, the neurochemical basis of this phenomenon is unknown. This study aimed to determine if an alteration at the receptor level could account for the contradictory findings in the imaging literature.  We looked at two neurotransmitter systems that have frequently been implicated in autism, GABA and serotonin (5HT).  

Objectives: To determine the density and laminar distribution of GABA_B receptors, benzodiazepine binding sites, and 5HT_1A receptors in the FFG in adult autistic and control cases.

Methods: Single concentration receptor binding autoradiography experiments were completed in the FFG using ³H-CGP54626 as a ligand for GABA_B receptors, ³H-flunitrazepam as a ligand for GABA_A receptor benzodiazepine (BZD) binding sites, and ³H-8OH-DPAT as a ligand for 5HT_1A receptors .  Autistic (n=10) and control (n=10) brains were matched for age and post-mortem interval.  Optical densities were measured in the superficial and deep layers using the Inquiry program.  Data analysis was conducted using Student’s t-test.

Results: GABA_B receptor density and BZD binding site density were significantly decreased in the superficial layers (p=0.007; p=0.02, respectively) in autistic cases.  In the deep layers there was a significant decrease (p=0.002) in the density of GABA_B receptors in the deep layers, but no change in BZD binding site density.  Additionally, there were significant reductions in the density of 5HT_1A receptors in both the superficial (p=0.02) and deep (p=0.04) layers in autistic cases.

Conclusions: A growing body of evidence suggests that individuals with autism have difficulties in face perception, implicating the FFG.  Recognition of persons, and especially their individual faces, is a key part of an individual’s social experience and successful functioning within a social group.  This study demonstrates decreased receptor density in the superficial and deep layers of the FFG in two key neurotransmitter systems, GABA and serotonin, in autism.  Abnormalities in the superficial layers suggest a disruption in cortiocortical connections, whereas abnormalities observed in the deep layers suggest altered efferent connectivity to sub-cortical regions. This study also provides important evidence regarding abnormalities in the GABAergic and serotonergic receptor systems, which may contribute to abnormal face processing in individuals with autism.

Acknowledgments:  Human tissue was obtained from the Harvard Brain and Tissue Resource Center, The Autism Research Foundation, and the NICHD Brain and Tissue Bank for Developmental Disorders.