Cortical interneuron dysfunction in epilepsy associated with autism spectrum disorders

Journal article

Autism and epilepsy are two associated disorders which are highly prevalent, share common developmental origins, and demonstrate substantial heritability. In this review, cross-disciplinary data in a rapidly evolving field that bridges neurology and psychiatry are synthesized to identify shared biological mechanisms. The relationship between these debilitating, lifelong conditions is examined at the clinical, genetic and neurophysiological levels in humans and in animal models. Scopus and Pubmed searches were used to identify relevant literature. Clinical observations have prompted speculation about the inter-dependence of autism and epilepsy, but causal relationships have proved difficult to determine. Despite their heritability the genetic basis of ASD and epilepsy has remained largely elusive until the advent of next generation sequencing. This approach has revealed that mutations that are either causal or confer an increased disease risk are found in numerous different genes any one of which accounts for only a small percentage of cases. Conversely, even cases with identical clinical phenotypes are genetically heterogeneous. Candidate gene identification has facilitated the development of mouse genetic models, which in parallel with human studies have implicated shared brain regions and circuits that mediate disease expression. Diverse genetic causes of ASD and epilepsy converge on cortical interneuron circuits as one important mediator of both disorders. Cortical interneurons are amongst the most diverse cell types in the brain and their unique chemical and electrical coupling exert a powerful inhibitory influence on excitatory neurons via the release of the neurotransmitter, gamma amino butyric acid (GABA). These multifaceted approaches have validated theories derived from the field of developmental neurobiology, which propose that the neurological and neuropsychiatric manifestations are due an altered ratio of excitation to inhibition in the cortex.

Authors: Jacob, J

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Wiley
• Journal: Epilepsia
• Volume: 57
• Issue: 2
• Pages: 182-193
• Publication date: 2015-12-19
• Acceptance date: 2015-11-05
• DOI: 10.1111/epi.13272
• EISSN: 1528-1167
• ISSN: 0013-9580
• Keywords: epilepsy; epileptic encephalopathy; GABA; autism spectrum disorder; cortical Interneuron