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.