Nicotinic Acetylcholine Receptor Alterations in Autism Spectrum Disorders – Biomarkers and Therapeutic Targets

Autism Spectrum Disorders (ASD) are a set of complex neurodevelopmental disorders defined behaviorally by impaired social interaction, delayed and disordered language, repetitive or stereotypic behavior and a restricted range of interest (Fombonne, 1999). ASD affect nearly 1 in 110 children, and disproportionally affect four times as many boys as girls. Comorbid symptoms often include seizures, sleep problems, gastrointestinal disorders, and metabolic deregulation (Coury, 2010). As such, ASD are an enormous challenge for parents, medical professionals, and educators. Their treatments put a significant financial strain on healthcare systems worldwide. There is no pharmacotherapy proven effective for treating the core deficits in ASD. There is also a paucity of biomarkers for autism. Both genetic and environmental factors are thought to contribute to autism susceptibility (Courchesne, 2007; Geschwind, 2009; Südhof, 2008; Ramocki & Zoghbi, 2008), but because only some of the genetic factors have been identified unequivocally thus far (Cook & Scherer, 2008; Levitt & Campbell, 2009), finding effective treatments that target the underlying causes of ASD remains a major challenge. Identifying endophenotypes and biomarkers for complex and heterogeneous disorders such as ASD are important not only to elucidate their etiologies, but also to identify suitable biochemical molecules and pathways to target the treatment of core deficits. In this review, we present a rationale that neuronal nicotinic acetylcholine receptor (nAChR) alterations are biomarkers for ASD and that specific nAChRs subtypes are likely to be useful therapeutic targets for the treatment of core deficits. This rationale is based on the synthesis of emerging evidence from multiple types of studies, including our own, using postmortem, genetic, functional, and molecular neurobiological methodologies from two disparate areas of research – autism spectrum disorders and nicotine dependence.