Pharmacotherapeutic implications of the association between genomic instability at chromosome 15q13.3 and autism spectrum disorders

Clin Neuropharmacol. 2011 Nov-Dec;34(6):203-5. doi: 10.1097/WNF.0b013e31823a1247.

Abstract

Recurrent microdeletions of chromosome 15q13.3 are causally associated with autism spectrum disorders (ASDs), suggesting that haploinsufficiency of CHRNA7, the gene that codes for the α7 nicotinic acetylcholine receptor (α7 nAChR) subunit, is an etiological mechanism. Independent of these genetic data, given the location of α7 nAChRs on γ-aminobutyric acid-inhibitory neurons and their role in maintaining central inhibitory tone, a compelling pharmacological rationale exists for therapeutically targeting the α7 nAChR in persons with ASDs. Given the availability of positive allosteric modulators of nicotinic acetylcholine receptors and selective agonists for the α7 nAChR (eg, choline derived from dietary administration of cytidine 5'diphosphocholine and anabasine derivatives), it is possible to conduct "proof of concept" clinical trials, exploring the effects of α7 nAChR agonist interventional strategies on domains of psychopathology, such as attention, cognition, and memory, in persons with ASDs.

Publication types

  • Review

MeSH terms

  • Animals
  • Child
  • Child Development Disorders, Pervasive / drug therapy*
  • Child Development Disorders, Pervasive / genetics*
  • Chromosomes, Human, Pair 15 / genetics*
  • Genetic Association Studies / trends*
  • Genomic Instability / drug effects
  • Genomic Instability / genetics*
  • Haploinsufficiency / drug effects
  • Haploinsufficiency / genetics
  • Humans
  • Nicotinic Agonists / therapeutic use*
  • Receptors, Nicotinic / genetics*
  • alpha7 Nicotinic Acetylcholine Receptor

Substances

  • Chrna7 protein, human
  • Nicotinic Agonists
  • Receptors, Nicotinic
  • alpha7 Nicotinic Acetylcholine Receptor