| Title: | Sociodemographic, clinical, and genetic factors associated with self-reported antidepressant response outcomes in the UK Biobank |
| Journal: | Psychological Medicine |
| Published: | 12 Mar 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40071563/ |
| DOI: | https://doi.org/10.1017/s0033291725000388 |
Publication 15618
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Abstract
BACKGROUND: 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.</p>
METHODS: In UK Biobank Mental Health Questionnaire 2, participants with MDD reported whether specific antidepressants helped them. We tested whether retrospective lifetime response to four selective serotonin reuptake inhibitors (SSRIs) (N = 19,516) - citalopram (N = 8335), fluoxetine (N = 8476), paroxetine (N = 2297) and sertraline (N = 5883) - was associated with sociodemographic (e.g. age, gender) and clinical factors (e.g. episode duration). Genetic analyses evaluated the association between CYP2C19 variation and self-reported response, while polygenic score (PGS) analysis assessed whether genetic predisposition to psychiatric disorders and antidepressant response predicted self-reported SSRI outcomes.</p>
RESULTS: 71%-77% of participants reported positive responses to SSRIs. Non-response was significantly associated with alcohol and illicit drug use (OR = 1.59, p = 2.23 × 10-20), male gender (OR = 1.25, p = 8.29 × 10-08), and lower-income (OR = 1.35, p = 4.22 × 10-07). The worst episode lasting over 2 years (OR = 1.93, p = 3.87 × 10-16) and no mood improvement from positive events (OR = 1.35, p = 2.37 × 10-07) were also associated with non-response. CYP2C19 poor metabolizers had nominally higher non-response rates (OR = 1.31, p = 1.77 × 10-02). Higher PGS for depression (OR = 1.08, p = 3.37 × 10-05) predicted negative SSRI outcomes after multiple testing corrections.</p>
CONCLUSIONS: Self-reported antidepressant response in the UK Biobank is influenced by sociodemographic, clinical, and genetic factors, mirroring clinical response measures. While positive outcomes are more frequent than remission reported in clinical trials, these self-reports replicate known treatment associations, suggesting they capture meaningful aspects of antidepressant effectiveness from the patient's perspective.</p>
21 Keywords
- Adult
- Aged
- Antidepressive Agents
- Biological Specimen Banks
- Citalopram
- Cytochrome P-450 CYP2C19
- Depressive Disorder, Major
- Female
- Fluoxetine
- Genetic Predisposition to Disease
- Humans
- Male
- Middle Aged
- Paroxetine
- Retrospective Studies
- Selective Serotonin Reuptake Inhibitors
- Self Report
- Sertraline
- Treatment Outcome
- UK Biobank
- United Kingdom
9 Authors
- Michelle Kamp
- Chris Wai Hang Lo
- Grigorios Kokkinidis
- Mimansa Chauhan
- Alexandra C. Gillett
- AMBER Research Team
- Andrew M. McIntosh
- Oliver Pain
- Cathryn M. Lewis
1 Application
| Application ID | Title |
|---|---|
| 82087 | Genetics and genetic epidemiology of brain-related traits and disorders, and their interplay with physical health |
Enabling scientific discoveries that improve human health