Identification of a naturally occurring 21 bp deletion in alpha 2c noradrenergic receptor gene and cognitive correlates to antipsychotic treatment.
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.
De Luca
Vincenzo
V
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
Vincent
John B
JB
Müller
Daniel J
DJ
Hwang
Rudi
R
Shinkai
Takahiro
T
Volavka
Jan
J
Czobor
Pal
P
Sheitman
Brian B
BB
Lindenmayer
Jean-Pierre
JP
Citrome
Leslie
L
McEvoy
Joseph P
JP
Lieberman
Jeffrey A
JA
Kennedy
James L
JL
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
C547774:ADRA2C protein, human; D014150:Antipsychotic Agents; D018341:Receptors, Adrenergic, alpha-2