Cortical Inhibition and GABAergic Function In Autism Spectrum Disorders

Background:  There is mounting evidence for the role of γ-aminobutyric acid (GABA) in the neuropathophysiology of autism spectrum disorders (ASD). An in vivo measure of GABA involves the use of transcranial magnetic stimulation (TMS) to the primary motor cortex to index cortical inhibition (CI). A preliminary TMS study of ASD found evidence of reduced CI among those diagnosed with high-functioning autism (although this finding did not extend to those diagnosed with Asperger’s disorder).

Objectives:  To conduct a comprehensive assessment of CI in ASD through the application of TMS to the motor cortices.

Methods:  Adolescents and young adults with ASD (n = 36) and matched controls (n = 34) were administered motor cortical TMS paradigms assessing several aspects of CI (thought to reflect activity at GABA_A and GABA_B receptors).

Results:  There were no differences in CI when comparing ASD and control groups. When comparing ASD subtypes, however, specific CI impairments were found among those who had experienced early language delays.

Conclusions:  These findings argue against a broad role for GABA in ASD, but indicate that disruption at GABA_A and GABA_B receptors may be involved in ASD where there is a delay in language acquisition. While clinical subtyping may be useful to better understanding the neurobiology of ASD, this research also has implications for the proposed use of GABA agonists in the treatment of ASD.