Impaired GABAergic Function in The Co-occurrence of Epilepsy and Autism Spectrum Disorders

Abstract

Background: Epilepsy occurs in around one percent of the general population. However, it is more prevalent in children with ASD. One hypothesis that explains this comorbidity is that compromised inhibitory GABA neurons function leads to neural hyper-excitation characteristic of ASD and epilepsy. This review investigated the association of GABA with comorbid ASD and epilepsy. Methods: PubMed and Scopus were searched for relevant articles according to criteria predefined by the reviewer. GABA (outcome) had to be assessed in ASD patients with epilepsy history (Exposure/population). Data was extracted in tables and a qualitative synthesis was performed. Risk of bias was assessed using the Newcastle-Ottawa assessment tool. Results: Six studies were included. Four post-mortem studies investigated the associations of GABAA and GABAB receptors with the occurrence of seizures in patients with ASD (N = 3-7). Several GABAA- and GABAB-R subunits were found to be reduced in brains of ASD patients with history of seizures compared to controls. However, reductions were also observed in ASD patients without seizures. The remaining two studies were gene association studies that investigated the association of variants in GABAA receptor genes with the occurrence of seizures in ASD patients (N = 2 and 41). Both studies indicated that GABAA-R B variants may be associated with the presence of seizures in autism. Discussion: This review was limited by the low number of studies, and unclear evidence due to small samples in the included studies. However, the genetic variants observed in GABA-Rs genes as well as the decreased protein expression warrant further investigation into the role of GABA in comorbid ASD and epilepsy.