Polygenic heterogeneity in antidepressant treatment and placebo response
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Dokumenter
- Fulltext
Forlagets udgivne version, 624 KB, PDF-dokument
The genetic architecture of antidepressant response is poorly understood. Polygenic risk scores (PRS), exploration of placebo response and the use of sub-scales might provide insights. Here, we investigate the association between PRSs for relevant complex traits and response to vortioxetine treatment and placebo using clinical scales, including sub-scales and self-reported assessments. We collected a clinical test sample of Major Depressive Disorder (MDD) patients treated with vortioxetine (N = 907) or placebo (N = 455) from seven randomized, double-blind, clinical trials. In parallel, we obtained data from an observational web-based study of vortioxetine-treated patients (N = 642) with self-reported response. PRSs for antidepressant response, psychiatric disorders, and symptom traits were derived using summary statistics from well-powered genome-wide association studies (GWAS). Association tests were performed between the PRSs and treatment response in each of the two test samples and empirical p-values were evaluated. In the clinical test sample, no PRSs were significantly associated with response to vortioxetine treatment or placebo following Bonferroni correction. However, clinically assessed treatment response PRS was nominally associated with vortioxetine treatment and placebo response given by several secondary outcome scales (improvement on HAM-A, HAM-A Psychic Anxiety sub-scale, CPFQ & PDQ), (P ≤ 0.026). Further, higher subjective well-being PRS (P ≤ 0.033) and lower depression PRS (P = 0.01) were nominally associated with higher placebo response. In the self-reported test sample, higher schizophrenia PRS was significantly associated with poorer self-reported response (P = 0.0001). The identified PRSs explain a low proportion of the variance (1.2–5.3%) in placebo and treatment response. Although the results were limited, we believe that PRS associations bear unredeemed potential as a predictor for treatment response, as more well-powered and phenotypically similar GWAS bases become available.
Originalsprog | Engelsk |
---|---|
Artikelnummer | 456 |
Tidsskrift | Translational Psychiatry |
Vol/bind | 12 |
Antal sider | 8 |
ISSN | 2158-3188 |
DOI | |
Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:
For the purpose of open access, this paper has been published under the creative common licence (CC-BY). This study was funded by Medical Research Council-UK (no. MC_A656_5QD30_2135), Maudsley Charity (no. 666), and Wellcome Trust (no. 094849/Z/10/Z) grants to OH and the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. AKN is funded by Innovation Fund Denmark (grant no. 8053-00004A). The views expressed are those of the author(s) and not necessarily those of H Lundbeck A/s, the NHS/NIHR or the Department of Health.
Funding Information:
The trials were conducted in collaboration between Takeda Pharmaceutical Company, Ltd. and H. Lundbeck A/S. AKN, AF, MV, and MD are employed by H. Lundbeck A/S. OH is a part-time employee and stockholder of H. Lundbeck A/S. OH has received investigator-initiated research funding from and/or participated in advisory/speaker meetings organized by Angellini, Autifony, Biogen, Boehringer-Ingelheim, Eli Lilly, Heptares, Global Medical Education, Invicro, Jansenn, Lundbeck, Neurocrine, Otsuka, Sunovion, Recordati, Roche and Viatris/ Mylan. OH has a patent for the use of dopaminergic imaging.
Publisher Copyright:
© 2022, The Author(s).
Antal downloads er baseret på statistik fra Google Scholar og www.ku.dk
ID: 324966160