Sociodemographic, clinical, and genetic factors associated with self-reported antidepressant response outcomes in the UK Biobank.

IF 5.9 2区医学 Q1 PSYCHIATRY

Psychological Medicine Pub Date : 2025-03-12 DOI:10.1017/S0033291725000388

Michelle Kamp, Chris Wai Hang Lo, Grigorios Kokkinidis, Mimansa Chauhan, Alexandra C Gillett, Andrew M McIntosh, Oliver Pain, Cathryn M Lewis

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引用次数: 0

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.

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.

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.

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.

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英国生物银行中与自我报告的抗抑郁反应结果相关的社会人口学、临床和遗传因素

背景：在重度抑郁障碍（MDD）中，只有~35%的患者在接受一线抗抑郁治疗后获得缓解。利用英国生物银行的数据，我们通过自我报告的结果确定抗抑郁反应的社会人口学、临床和遗传预测因素，旨在为个性化治疗策略提供信息。方法：在英国生物银行心理健康问卷2中，重度抑郁症患者报告了特定抗抑郁药物是否对他们有帮助。我们测试了四种选择性血清素再摄取抑制剂（SSRIs）（N = 19,516）——西酞普兰（N = 8335）、氟西汀（N = 8476）、帕罗西汀（N = 2297）和瑟曲林（N = 5883）的回顾性终生反应是否与社会人口学（如年龄、性别）和临床因素（如发作持续时间）相关。遗传分析评估CYP2C19变异与自我报告反应之间的关系，而多基因评分（PGS）分析评估精神疾病和抗抑郁反应的遗传易感性是否预测自我报告的SSRI结果。结果：71%-77%的参与者报告了对SSRIs的积极反应。无应答与酒精和非法药物使用（OR = 1.59, p = 2.23 × 10-20）、男性（OR = 1.25, p = 8.29 × 10-08）和低收入（OR = 1.35, p = 4.22 × 10-07）显著相关。最糟糕的发作持续2年以上（OR = 1.93, p = 3.87 × 10-16）和积极事件没有改善情绪（OR = 1.35, p = 2.37 × 10-07）也与无反应相关。CYP2C19代谢不良者名义上无反应率更高（OR = 1.31, p = 1.77 × 10-02）。经多次检验校正后，抑郁症患者较高的PGS （OR = 1.08, p = 3.37 × 10-05）预测SSRI结果为阴性。结论：在英国生物银行中，自我报告的抗抑郁反应受到社会人口学、临床和遗传因素的影响，反映了临床反应措施。虽然临床试验中报告的积极结果比缓解更常见，但这些自我报告重复了已知的治疗关联，表明它们从患者的角度捕捉了抗抑郁药有效性的有意义的方面。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Psychological Medicine 医学-精神病学

CiteScore

11.30

自引率

4.30%

发文量

711

审稿时长

3-6 weeks

期刊介绍： Now in its fifth decade of publication, Psychological Medicine is a leading international journal in the fields of psychiatry, related aspects of psychology and basic sciences. From 2014, there are 16 issues a year, each featuring original articles reporting key research being undertaken worldwide, together with shorter editorials by distinguished scholars and an important book review section. The journal''s success is clearly demonstrated by a consistently high impact factor.