Understanding genetic risk factors for common side effects of antidepressant medications

作者：Adrián I. Campos, Aoibhe Mulcahy, Jackson G. Thorp, Naomi R. Wray, Enda M. Byrne, Penelope A. Lind, Sarah E. Medland, Nicholas G. Martin, Ian B. Hickie, Miguel E. Rentería · 发表于：Communications Medicine · 年份：2021 · DOI：10.1038/s43856-021-00046-8 · 被引用次数：63 · 研究领域：Genetic Associations and Epidemiology、Treatment of Major Depression、Cognitive Abilities and Testing

Background: Major depression is one of the most disabling health conditions internationally. In recent years, new generation antidepressant medicines have become very widely prescribed. While these medicines are efficacious, side effects are common and frequently result in discontinuation of treatment. Compared with specific pharmacological properties of the different medications, the relevance of individual vulnerability is understudied. Methods: We used data from the Australian Genetics of Depression Study to gain insights into the aetiology and genetic risk factors to antidepressant side effects. To this end, we employed structural equation modelling, polygenic risk scoring and regressions. Results: Here we show that participants reporting a specific side effect for one antidepressant are more likely to report the same side effect for other antidepressants, suggesting the presence of shared individual or pharmacological factors. Polygenic risk scores (PRS) for depression associated with side effects that overlapped with depressive symptoms, including suicidality and anxiety. Body Mass Index PRS are strongly associated with weight gain from all medications. PRS for headaches are associated with headaches from sertraline. Insomnia PRS show some evidence of predicting insomnia from amitriptyline and escitalopram. Conclusions: Our results suggest a set of common factors underlying the risk for antidepressant side effects. These factors seem to be partly explained by genetic li...