5-HT2A receptor promoter polymorphism, -1438G/A and negative symptom response to olanzapine in schizophrenia.
The 5-HT2A receptor promoter -1438G/A polymorphism, which is in complete linkage disequilibrium with the 5-HT2A 102T/C polymorphism, may be related to antipsychotic response. The aim of this paper is to determine relationships between the -1438G/A polymorphism and olanzapine negative symptom response. DNA from 41 subjects with schizophrenia (as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) was analyzed for the -1438G/A polymorphism. Olanzapine (7.5-20 mg/day) was given for 6 weeks and response was assessed using the Scale for Assessment of Negative Symptoms (SANS). A linear regression used a dependent variable of percent change in SANS. Independent variables included 5-HT2A polymorphisms and interactions. The -1438G/A polymorphism and percent change in SANS showed a significant trend (P=.0542). The A/A genotype group had a 45% reduction in SANS compared with 19% in the other groups. We conclude that the A/A genotype may be associated with olanzapine negative symptom response, seen as a 2-fold greater percent reduction in SANS, and may be clinically relevant.
Ellingrod
Vicki L
VL
Clinical and Administrative Division, University of Iowa College of Pharmacy, Iowa City, Iowa, USA. vicki-ellinrod@uiowa.edu
Lund
Brian C
BC
Miller
Del
D
Fleming
Frank
F
Perry
Paul
P
Holman
Timothy L
TL
Bever-Stille
Kristy
K
D014150:Antipsychotic Agents / Q000009:adverse effects*; D001569:Benzodiazepines; D005838:Genotype; D006801:Humans; D000077152:Olanzapine; D010890:Pirenzepine / Q000009:adverse effects* / Q000031:analogs & derivatives*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics*; D012559:Schizophrenia / Q000150:complications*; D012565:Schizophrenic Psychology; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D000077152:Olanzapine; D010890:Pirenzepine; D044402:Receptor, Serotonin, 5-HT2A; D017367:Selective Serotonin Reuptake Inhibitors