PROJECT: JTC2010: PADRE

Project aim: This project aims to develop and validate a functional antidepressant drug response assay, based on an individual''s genomic and transcriptomic information, for assessing pharmacogenomic variability between individuals and developing diagnostic tools for personalized treatment of major depression. Work plan: Growth inhibition by different classes of antidepressants will be compared systematically in human lymphoblastoid cell lines (LCLs) of the Israel National Laboratory for the Genetics of Israeli Populations. Tentative gene-expression markers for drug effects together with candidate genes from the recent genome wide clinical antidepressant drug response studies will be functionally characterized and differences in transcriptomics will be compared in LCLs and primary blood lymphocytes from individual patients clinically characterized for antidepressant drug response. Tentative biomarkers of drug response will then be transformed to a pharmacogenetic diagnostic test which will be studied and validated in large cohorts of patients characterized for antidepressant drug response. Exploitation of the results: This project is situated in the gap between the complex clinical situation of antidepressant drug therapy in major depression, and modern genome-wide tools for functional pharmacogenetic assays. It serves the need to individually predict which of the several available antidepressant drug classes will work most likely in an individual depressed patient.