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Figure 1. Impact of SULT4A1-1 haplotype status on weight gain in CATIE. Mean monthly weight change was calculated for SULT4A1-1 positive (n = 23) and negative (n = 64) olanzapine-treated subjects as well as subjects treated with other atypical antipsychotics (quetiapine, risperidone and ziprasidone; n = 330). The solid bars and the numbers above the error bars represent the mean monthly change. The error bars represent the standard error of each group. p-values represent the results of a t-test between the means of the two groups linked by the bar.
(Figure omitted. See article PDF.)
Background
The economic, medical and social burden of treating serious mental illness has remained extremely high even after the introduction of numerous new antipsychotic treatments in the last few years [1]. Hundreds of thousands of individuals suffering from mental illness are hospitalized each year with a cost in the tens of billions of US dollars [1,2]. Thus, the ability to identify which antipsychotics are most likely to benefit a given patient would represent a significant improvement in the treatment of mental illness.
Numerous genome-wide association studies and candidate gene studies have attempted to identify markers of antipsychotic response, but few, if any, markers have produced consistent, replicated results [3-10]. Several studies of markers in candidate genes such as DRD3 [11], KCNH2 [12], HTR2A [13,14] and SV2C [15] have produced positive findings for olanzapine response. However, these markers lack either sufficient replication or have various inconsistencies that limit their current usefulness in clinical practice. In particular, interstudy differences in the genetic models that predict superior response and differences in phenotypes (e.g., positive vs negative symptoms) have limited the clinical utility of these markers for making informed medication selection decisions despite a reasonable likelihood that they do impact olanzapine response in some manner.
A specific haplotype of the SULT4A1 gene called SULT4A1-1 has been reported to correlate with superior response to olanzapine [16]. In the original report, the haplotype displayed both a consistent phenotype, that is, superior response to olanzapine for reduction of total psychopathology symptom burden, and a consistent genetic model in Phase 1 of CATIE and in an independent clinical sample from Vanderbilt University. Individuals with at least one copy of SULT4A1-1 were classified as SULT4A1-1 positive. In both...