title: Pharmacotherapeutic implications of the association between genomic instability at chromosome 15q13.3 and autism spectrum disorders.
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.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Eastern Virginia Medical School, Norfolk, Virginia 23507-1912, USA. deutscsi@evms.edu
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Deutsch
authors.forename: Maria R
authors.initials: MR
authors.lastname: Urbano
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Burket
authors.forename: Amy L
authors.initials: AL
authors.lastname: Herndon
authors.forename: Erin E
authors.initials: EE
authors.lastname: Winebarger
mesh_terms: D000818:Animals; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000188:drug therapy* / Q000235:genetics*; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D056726:Genetic Association Studies / Q000639:trends*; D042822:Genomic Instability / Q000187:drug effects / Q000235:genetics*; D057895:Haploinsufficiency / Q000187:drug effects / Q000235:genetics; D006801:Humans; D018722:Nicotinic Agonists / Q000627:therapeutic use*; D011978:Receptors, Nicotinic / Q000235:genetics*; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579167:Chrna7 protein, human; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor