title: Identification of a naturally occurring 21 bp deletion in alpha 2c noradrenergic receptor gene and cognitive correlates to antipsychotic treatment.
abstract: Neurocognitive deficits are recognized as a cardinal feature of schizophrenia. Atypical antipsychotics have high affinity for many neurotransmitter receptors. Among these receptors, antipsychotics are antagonists of adrenoceptors, and this pharmacological property has been postulated to be involved in the mechanism of action of antipsychotics. We tested the hypotheses that clinical response and cognitive improvement to antipsychotic treatment are associated with genetic variation in adrenergic alpha2C receptor (ADRA2C). Fifty-seven patients with chronic schizophrenia were prospectively assessed for clinical response to antipsychotic treatment. They were subsequently genotyped for a 21 bp insertion/deletion that we identified in the 3' untranslated region (3'UTR) of ADRA2C. With regard to clinical response and cognitive improvement to antipsychotics, there was no significant association observed for this polymorphism. Our results suggest that the novel polymorphism may not play a major role in antipsychotic response.
authors.affiliation: Neurogenetics Section, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, 250 College Street R-30, Toronto, Ont., Canada M5T 1R8. vincenzo_deluca@camh.net
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Luca
authors.forename: John B
authors.initials: JB
authors.lastname: Vincent
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Müller
authors.forename: Rudi
authors.initials: R
authors.lastname: Hwang
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shinkai
authors.forename: Jan
authors.initials: J
authors.lastname: Volavka
authors.forename: Pal
authors.initials: P
authors.lastname: Czobor
authors.forename: Brian B
authors.initials: BB
authors.lastname: Sheitman
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Lindenmayer
authors.forename: Leslie
authors.initials: L
authors.lastname: Citrome
authors.forename: Joseph P
authors.initials: JP
authors.lastname: McEvoy
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Lieberman
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
mesh_terms: D000483:Alleles; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D020029:Base Pairing / Q000235:genetics; D003072:Cognition Disorders / Q000188:drug therapy* / Q000235:genetics*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D017384:Sequence Deletion
chemical_list: C547774:ADRA2C protein, human; D014150:Antipsychotic Agents; D018341:Receptors, Adrenergic, alpha-2