Molecular Basis of Cholinergic Changes in Autism Spectrum Disorders and Relevance for Treatment Interventions

Abstract

The causes of autism are heterogeneous and still largely unknown. Cholinergic abnormalities are reported in molecular pathological studies conducted on brain tissues from adults with autism and may explain the numerous cognitive and behavioural changes seen in the autism spectrum disorders (ASD), including impairment in various cognitive domains, memory and attention. Currently available treatments for the behavioural problems frequently reported in children and adults with ASD are largely for symptomatic relief of irritability, hyperactivity and repetitive stereotyped behaviour. In this review we address current knowledge about the cholinergic changes in ASD and how these are relevant in clinical setting. In particular, we review the prospect of the use of cholinesterase inhibitors and other cholinomimetics (chemicals that can act by either directly stimulating the nicotinic or muscarinic receptors, or promote acetylcholine release) in ASD for treatment of both cognitive and behavioural changes, based on their benefits in neurodegenerative (e.g. Alzheimer’s disease and Lewy Body Spectrum Diseases) and neurodevelopmental disorders (e.g. schizophrenia and Down syndrome). As a result, we provide an overview of the current use of cholinesterase inhibitors (donepezil, galantamine and rivastigmine) and cholinomimetics (e.g. nicotine) in the treatment of cognitive and behavioral symptoms in ASD, and discuss developments of novel cholinergic drug interventions that can safely target core disease mechanisms as early as possible.