AMBER: Antidepressant Medications: Biology, Exposure & Response
The AMBER study (Antidepressant Medications: Biology, Exposure & Response) is a Wellcome-funded Mental Health Award that aims to identify the causal determinants of antidepressant response (2023-2028). The multidisciplinary AMBER team integrates clinical, genomic, cellular and patient-participatory research to gain insight into antidepressant action and response, enhance our understanding of drug mechanisms and biological pathways, and develop predictive models building towards personalised prescribing to improve patient outcomes.
Our research is carried out in collaboration with people who have lived experience of depression and antidepressant treatment. This partnership aims to increase trust, ensure the relevance and significance of our research, and improve the dissemination and impact of the research findings.
King’s investigators, Cathryn Lewis and Oliver Pain, work in collaboration with researchers at the University of Edinburgh (Andrew McIntosh, Heather Whalley, Sue Fletcher-Watson) and the University of Queensland (Sonia Shah, Quan Nguyen, Naomi Wray) to achieve this ambitious project.
Aims
- Work with our Lived Experience Advisory Panel to guide our research programme and engage with patients and communities to understand the diverse experiences of depression and treatment.
- Use real-world data from electronic health care records to develop robust and reproducible measures of antidepressant exposure and response.
- Conduct genome-wide association studies to explore genetic influences of antidepressant exposure and response.
- Perform DNA methylation, proteomic and metabolomic association studies of antidepressant exposure to understand the effects of antidepressants on molecular phenotypes.
- Identify genetic associations, polygenic profiles and biological pathways of antidepressant response.
- Undertake cellular genomic studies to further understand the impacts of antidepressant treatment.
Highlights to date
To date, we’ve made the following progress:
- Set up a Lived Experience Advisory Panel and carried out a scoping exercise to connect with community organisations for impactful research.
- Held focus groups with GPs to explore their views on using open-text data from electronic health records in research, and surveyed clinicians on depression treatment and response.
- Started analysing Generation Scotland prescribing data, mapping antidepressant switches, treatment durations, and defining early phenotypes for Treatment Resistant Depression and Antidepressant Maintenance.
- Partnered with EU researchers in the REALMENT project to standardise antidepressant treatment response phenotypes (review article submitted).
- Collaborated on how data availability (e.g., SAIL Databank) affects phenotyping approaches.
- Carried out studies on the proteome, DNA methylation and genome-wide associations related to antidepressant exposure, currently expanding to include All of Us data.
- Developed two new proxy phenotypes for SSRI non-response: antidepressant switching from prescribing records and self-reported treatment response (manuscripts under review).
- Acquired commercial human cell lines and procured three standard SSRIs, plus one designed for better cell permeability, to study drug-cell interactions.
- Genotyped commercial cell lines for CYP2C19 variants to optimise experimental designs and understand genetic impacts on SSRI responses.
To read more about AMBER and our aims, check out the University of Edinburgh blog and read our poster.
We welcome new collaborators with relevant data sources on any aspect of antidepressants: email cathryn.lewis@kcl.ac.uk.
Principal Investigator
Professor of Genetic Epidemiology & Statistics