52. Reverse pharmacogenetics: a new approach to rapid relapse in schizophrenia?

Abstract

A significant subgroup of patients with schizophrenia experience rapid exacerbations in clinical symptoms following antipsychotic drug discontinuation. There are limited clinical or biological data with which to predict which patients are at increased risk for rapid relapse. New assessment tools that provide more accurate risk-benefit profiles for individual patients may be of use in determining clinical management strategies of patients at high risk for medication discontinuation. Previously, we have examined the role of a functional polymorphism (5-HTTLPR) in the serotonin transporter gene in antipsychotic drug-free patients participating in a placebo-controlled clinical trial. In this study, the clinical profile of 50 schizophrenia patients was assessed with the Brief Psychiatric Rating Scale (BPRS) after 4 weeks of placebo administration. Analysis by genotype revealed that the 5-HTTLPR ll genotype was markedly over-represented in the group of patients with increased BPRS ratings of positive symptoms (p = 0.0003). Patients with the 5-HTTLPR ll genotype were also observed to experience greater negative symptoms, anxiety and depression BPRS ratings. Although these data are preliminary, they suggest that studies of genetic variation may provide a means to identify schizophrenia patients at high risk for rapid relapse following drug discontinuation. New studies are underway to assess the merits of this reverse pharmacogenetics approach.