Pharmacogenomics

The primary objective of the clinical research of pharmacogenomics is to better understand genetic variability as it relates to antidepressant response. The team is involved in both psychiatric pharmacogenomics and pharmacogenomic testing for algorithm research.

Projects

  • Pharmacogenomics and pharmacodynamics of selective serotonin reuptake inhibitors (SSRIs). This project has been supported since 2005 by the National Institute of General Medical Sciences, and nearly 800 patients have been studied. A second arm of this research is studying the use of a serotonin and norepinephrine reuptake inhibitor (SNRI), duloxetine (Cymbalta), in patients who did not have remission when treated with escitalopram or citalopram.
  • Pharmacogenomics and genome studies collaboration. In 2010, the RIKEN Institute in Japan conducted a genome-wide association study of the initial Pharmacogenomic Research Network (PGRN) patient cohort of 398 patients. A number of gene variants were associated with response, and functional studies of these variants are complete. The next step is to conduct a large, genome-wide study of more than 1,400 samples that have been collected within the newly established International SSRI Pharmacogenomics Consortium.
  • Induced pluripotent stem (iPS) cell research. Yuan Ji, Ph.D., leads this study with the PGRN team, researching iPS cells in depressed patients treated with SSRIs. The team has partnered with Timothy J. Nelson, M.D., Ph.D., and colleagues at the University of Minnesota and the Salk Institute for Biological Studies to study a subset of patients who have been in the PGRN SSRI study.

    First reported in 2007, iPS cells accomplish two important tasks. First, they convert adult skin cells into stem cells (cells capable of growing into many cell types). Second, these cells can be differentiated into neurons or other mature cell types. This technology provides the means to reprogram patients' skin cells into their own neurons, theoretically allowing an understanding of either an individual's response to treatment or how to engineer a personalized plan.

The team has completed numerous other projects, including a pharmacometabolomics study of escitalopram and citalopram response. Additional analyses are underway with colleagues at the University of North Carolina; the University of California, Davis; and the Edith Nourse Rogers Memorial Veterans Hospital in Bedford, Mass.

Investigators

Grants

Investigator & Role Grant Title Funding Source Duration
Richard Weinshilboum, M.D., principal investigator Pharmacogenetics of Phase II Drug Metabolizing Enzymes National Institute of General Medical Sciences 07/2010-06/2015
Richard Weinshilboum, M.D., principal investigator PGRN Pharmacogenomic Ontology Network Resource National Institute of General Medical Sciences 07/2013-06/2014