Anil K. Malhotra, Hillside Hospital,

Albert Einstein College of Medicine

The introduction of molecular genetic techniques into

psychiatric research has provided the impetus for renewed attempts to identify

psychotropic drug response predictors.  This field of inquiry, often called

pharmacogenetics or pharmacogenomics, offers the prospect of the identification

of easily accessible biological predictors of antipsychotic drug response and

may provide information about the molecular substrates of drug efficacy. Initial

data in this regard, however, have been inconsistent, perhaps secondary to

relatively small sample sizes, the use of retrospective, non-specific

assessments of outcome, and the problem of ethnic stratification within study

groups.  Moreover, these initial studies have only included a limited

number of single nucleotide polymorphisms (SNPs) – primarily due to the paucity

of data on genetic variation and limitations in genotyping capabilities. 

Over the past two years, the dramatic increase in genomic information and

concomitant improvements in molecular technology have provided the means to

markedly enhance pharmacogenetic studies.  For example, complete sequence

data is now available for more than 10,000 genes and over 5,000,000 SNPs have

markedly reduced the expense of genotyping.  These developments, coupled

with new statistical approaches and the introduction of routine DNA collection

into large-scale clinical trials, suggest that comprehensive whole genome

association studies of psychotropic drug response are now feasible to

consider.  In this presentation, we will review the first generation of

genetic studies of antipsychotic drug response, examine the new developments in

pharmacogenomics, and discuss strategies for utilizing pharmacogenomic

techniques in new drug development.