Objective This project will address the emerging healthcare problem of Treatment Resistant Depression (TRD). Major Depressive Disorder (MDD) is a major social and clinical burden, responsible for ~15% of all days lived with disability in EU. Treatment challenges arise from the different biological dysfunctions implicated in different patients and the lack of biomarkers available to guide the choice of anti-depressants. Preliminary evidence suggests that genetic variants may be useful in making treatment choices, but further work to identify relevant variants is needed. Previous pharmacogenetic studies have focused on identifying common genetic variants associated with antidepressant response. The role of rare variants has not been well studied and few studies have investigated the genetics of TRD (patients with two or more failed treatments). This project will combine exome sequencing and genome-wide genotyping in the unique GSRD sample of 1346 MDD patients characterized for stages of treatment resistance (number of failed treatments). This study aims to identify both rare and common variants associated with stages of resistance, the first such study to be performed. The analysis will focus on genes and pathways instead of single variants, since the cumulative effect of a number of variants is likely to disrupt the functionality of a gene or pathway. The study will assess the impact of clinical variables on genetic finding, and develop a genomic profile for TRD which can be used to guide treatment in patients. These findings will be used to design a prospective clinical trial to test the cost-effectiveness of the TRD genetic markers. I will seek funding sources to implement the trial, an essential step to translate the findings to the clinic. This personalised medicine study should facilitate the development of new evidence-based treatments and substantially reduce the time to identify the best treatment strategy in MDD. Fields of science natural sciencesbiological sciencesneurobiologymedical and health sciencesclinical medicinepsychiatrymedical and health sciencesbasic medicineneurology Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2017 - Individual Fellowships Call for proposal H2020-MSCA-IF-2017 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator KING'S COLLEGE LONDON Net EU contribution € 137 591,10 Address STRAND WC2R 2LS London United Kingdom See on map Region London Inner London — West Westminster Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 137 591,10
