Identifying the Common Genetic Basis of Antidepressant Response

Antidepressants are a first-line treatment for depression. However, only a third of individuals experience remission after the first treatment. Common genetic variation, in part, likely regulates antidepressant response, yet the success of previous genome-wide association studies has been limited by sample size. This study performs the largest genetic analysis of prospectively assessed antidepressant response in major depressive disorder to gain insight into the underlying biology and enable out-of-sample prediction.

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Paper: Pain O, Hodgson K, Trubetskoy V, et al. Identifying the Common Genetic Basis of Antidepressant Response. Biol Psychiatry Glob Open Sci. 2022;2(2):115-126.


Antidepressant response and CYP enzyme metabolizer statuses

Cytochrome P450 enzymes including CYP2C19 and CYP2D6 are important for antidepressant metabolism and polymorphisms of these genes have been determined to predict metabolite levels. Nonetheless, more evidence is needed to understand the impact of genetic variations on antidepressant response.

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Paper: Li, D., Pain, O., Fabbri, C. et al. Metabolic activity of CYP2C19 and CYP2D6 on antidepressant response from 13 clinical studies using genotype imputation: a meta-analysis. Transl Psychiatry 14, 296 (2024).


Self-reported antidepressant response outcomes in UK Biobank

In major depressive disorder (MDD), only ~35% achieve remission after first-line antidepressant therapy. Using UK Biobank data, we identify sociodemographic, clinical, and genetic predictors of antidepressant response through self-reported outcomes, aiming to inform personalized treatment strategies.

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Preprint: Kamp M, Lo C, Kokkinidis G, Chauhan M, Gillett A, Pain O et al. Sociodemographic, clinical, and genetic factors associated with self-reported antidepressant response outcomes in the UK Biobank. Psychological Medicine. 2025 Jan 20.


Antidepressant switching in UK Biobank and Generation Scotland

Selective serotonin reuptake inhibitors (SSRIs) are a first-line pharmacological therapy in major depressive disorder (MDD), but treatment response rates are low. Clinical trials lack the power to study the genetic contribution to SSRI response. Real-world evidence from electronic health records provides larger sample sizes, but novel response definitions are needed to accurately define SSRI non-responders.

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Preprint: Lo, Chris Wai Hang, Alexandra C. Gillett, Matthew H. Iveson, Michelle Kamp, Chiara Fabbri, Win Lee Edwin Wong, Dale Handley et al. “Antidepressant Switching as a Proxy Phenotype for Drug Nonresponse: Investigating Clinical, Demographic, and Genetic Characteristics.” Biological Psychiatry Global Open Science 5, no. 4 (2025): 100502.