INTEGRATING LIVED EXPERIENCE, GENOMICS AND CLINICAL DATA TO UNDERSTAND ANTIDEPRESSANT RESPONSE

Overall Abstract Antidepressants are the most widely prescribed psychotropic medications, but individual response rates are low and we lack predictors of who will respond effectively, to which antidepressants. This has led to reduced public faith in the value of antidepressants. This Symposium will report research from the Wellcome-funded AMBER (Antidepressant Medications: Biology, Exposure and Response) Study, which integrates clinical, genomic, cellular and patient-participatory research to gain insight into antidepressant action and response. The talks will report our cross-disciplinary work to on building frameworks necessary to enhance our understanding of antidepressant use and response. These building blocks are an essential component of moving towards personalised prescribing to improve patient outcomes. Our first talk will be from Cristina Douglas (University of Edinburgh) and members of the AMBER Lived Experience Advisory Panel. They will on focus groups with people with experience of taking anti-depressants, asking about their views on genetic research and (in the future) genetic testing in the context of prescribing anti-depressants. This work showcases our participatory approach, with LEAP participants fully integrated in the research, from co-leading focus groups to analysis and interpretation. The second speaker is Michelle Kamp (King’s College London) who will report on a genome-wide association study of self-reported response to antidepressants. This retrospective measure captures whether the user felt the drug was helpful, giving a more comprehensive response than captured at a clinical trial end-point. The study will integrate over 35,000 participants from UK Biobank, All of Us, AGDS, and GLAD studies. Dr Matthew Iveson (University of Edinburgh), will present work on extracting phenotypes for depression-treatment and response from both structured and unstructured data in electronic health records. This work enables strong response variables to be constructed, and has been guided by clinician workshops, enabling a deeper understanding of their use of electronic health records. Our final talk, from Hannah Smith (University of Edinburgh), will present work on potential biomarkers of exposure to antidepressants, including DNA methylation, proteins and metabolites. The presentation will highlight gaps in our knowledge as well as recent advances, including newly available data on antidepressant exposure and response in Generation Scotland. Together these talks will highlight both the opportunities available from large scale clinical and biological data to characterise the response to antidepressants, and the importance of undertaking research with people with lived experience, enriching relevance and outcomes. Our discussant will be Lea Davis, who brings the breadth of scientific expertise to integrate these diverse perspectives into a progress on understanding how antidepressants work, and for whom.