Genetic Confounding of the Association Between Age at First Hormonal Contraception and Depression.

IF 5.3 2区医学 Q1 PSYCHIATRY

Acta Psychiatrica Scandinavica Pub Date : 2025-01-02 DOI:10.1111/acps.13774

Jessica Mundy, Alisha S M Hall, Esben Agerbo, Clara Albiñana, Jette Steinbach, Bjarni J Vilhjálmsson, Søren D Østergaard, Katherine L Musliner

{"title":"Genetic Confounding of the Association Between Age at First Hormonal Contraception and Depression.","authors":"Jessica Mundy, Alisha S M Hall, Esben Agerbo, Clara Albiñana, Jette Steinbach, Bjarni J Vilhjálmsson, Søren D Østergaard, Katherine L Musliner","doi":"10.1111/acps.13774","DOIUrl":null,"url":null,"abstract":"Background: Previous research has shown that females who use hormonal contraception are at increased risk of developing depression, and that the risk is highest among adolescents. While this finding could reflect age-specific effects of exogenous hormones on mental health, genetic liability for mental disorders could be confounding the association. Our goal was to test the plausibility of this hypothesis by determining whether polygenic liabilities for major depressive disorder (MDD), bipolar disorder (BD), schizophrenia (SCZ), and attention deficit hyperactivity disorder (ADHD) are associated with younger age at hormonal contraception initiation.Methods: We conducted a cohort study using data from the Danish iPSYCH2015 sub-cohort, a representative sample of people born in Denmark between May 1981 and December 2008. Polygenic scores (PGSs) for MDD, BD, SCZ, and ADHD were created using the most recent genome-wide association study meta-analyses from the Psychiatric Genomics Consortium. Associations between PGSs and hormonal contraception initiation in the following age categories: 10-14, 15-19, 20-24, and 25+ were examined via Cox regression. We examined any hormonal contraception, oral contraception, and non-oral contraception.Results: PGS-MDD and PGS-ADHD showed the strongest associations with hormonal contraception initiation at age 10-14 (PGS-ADHD: HR = 1.21 [95% CI = 1.16-1.27], p = 6.16 x 10-18; PGS-MDD: 1.21 [1.16-1.27], p = 1.22 x 10-17). The associations then steadily decreased as age at hormonal contraception initiation increased. Both PGS-MDD and PGS-ADHD were also associated with initiation at ages 15-19, but not at 20-24 or 25+. PGS-BD and PGS-SCZ were also associated, albeit not as strongly, with initiation at age 10-14 only (PGS-BD: 1.07 [1.02-1.13], p = 6.87 × 10-3; PGS-SCZ: 1.09 [1.04-1.14], p = 8.61 × 10-4).Conclusions and relevance: These results suggest that genetic confounding could explain some of the association between early hormonal contraception use and depression. Where possible, researchers studying this important topic should account for possible confounding by genetic liability for mental disorders.","PeriodicalId":108,"journal":{"name":"Acta Psychiatrica Scandinavica","volume":" ","pages":""},"PeriodicalIF":5.3000,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Psychiatrica Scandinavica","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/acps.13774","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Previous research has shown that females who use hormonal contraception are at increased risk of developing depression, and that the risk is highest among adolescents. While this finding could reflect age-specific effects of exogenous hormones on mental health, genetic liability for mental disorders could be confounding the association. Our goal was to test the plausibility of this hypothesis by determining whether polygenic liabilities for major depressive disorder (MDD), bipolar disorder (BD), schizophrenia (SCZ), and attention deficit hyperactivity disorder (ADHD) are associated with younger age at hormonal contraception initiation.

Methods: We conducted a cohort study using data from the Danish iPSYCH2015 sub-cohort, a representative sample of people born in Denmark between May 1981 and December 2008. Polygenic scores (PGSs) for MDD, BD, SCZ, and ADHD were created using the most recent genome-wide association study meta-analyses from the Psychiatric Genomics Consortium. Associations between PGSs and hormonal contraception initiation in the following age categories: 10-14, 15-19, 20-24, and 25+ were examined via Cox regression. We examined any hormonal contraception, oral contraception, and non-oral contraception.

Results: PGS-MDD and PGS-ADHD showed the strongest associations with hormonal contraception initiation at age 10-14 (PGS-ADHD: HR = 1.21 [95% CI = 1.16-1.27], p = 6.16 x 10^-18; PGS-MDD: 1.21 [1.16-1.27], p = 1.22 x 10^-17). The associations then steadily decreased as age at hormonal contraception initiation increased. Both PGS-MDD and PGS-ADHD were also associated with initiation at ages 15-19, but not at 20-24 or 25+. PGS-BD and PGS-SCZ were also associated, albeit not as strongly, with initiation at age 10-14 only (PGS-BD: 1.07 [1.02-1.13], p = 6.87 × 10^-3; PGS-SCZ: 1.09 [1.04-1.14], p = 8.61 × 10^-4).

Conclusions and relevance: These results suggest that genetic confounding could explain some of the association between early hormonal contraception use and depression. Where possible, researchers studying this important topic should account for possible confounding by genetic liability for mental disorders.

查看原文本刊更多论文

第一次激素避孕年龄与抑郁症之间关系的遗传混淆。

背景：以往的研究表明，使用荷尔蒙避孕药的女性患抑郁症的风险增加，而青少年患抑郁症的风险最高。虽然这一发现可能反映了外源性激素对心理健康的年龄特异性影响，但精神障碍的遗传责任可能会混淆这种关联。我们的目标是通过确定重性抑郁症（MDD）、双相情感障碍（BD）、精神分裂症（SCZ）和注意缺陷多动障碍（ADHD）的多基因遗传责任是否与开始使用激素避孕的年龄较小有关，来检验这一假设的合理性：我们利用丹麦 iPSYCH2015 子队列的数据进行了一项队列研究，该子队列是 1981 年 5 月至 2008 年 12 月间在丹麦出生的代表性样本。我们利用精神疾病基因组学联盟（Psychiatric Genomics Consortium）最新的全基因组关联研究荟萃分析，创建了MDD、BD、SCZ和ADHD的多基因评分（PGS）。PGSs与以下年龄段开始使用激素避孕药之间存在关联：10-14岁、15-19岁、20-24岁：我们通过 Cox 回归分析了 10-14、15-19、20-24 和 25 岁以上年龄组的 PGS 与开始使用激素避孕之间的关系。我们对任何激素避孕、口服避孕和非口服避孕进行了研究：结果：PGS-MDD 和 PGS-ADHD 与 10-14 岁开始使用激素避孕的关系最为密切（PGS-ADHD：HR = 1.21 [95% CI = 1.16-1.27]，p = 6.16 x 10-18；PGS-MDD：1.21 [1.16-1.27]，p = 1.22 x 10-17）。随后，随着开始使用激素避孕的年龄增加，相关性逐渐降低。PGS-MDD 和 PGS-ADHD 也与 15-19 岁开始使用激素避孕有关，但与 20-24 岁或 25 岁以上开始使用激素避孕无关。PGS-BD和PGS-SCZ也与10-14岁开始使用激素避孕有关，尽管没有那么强（PGS-BD：1.07 [1.02-1.13]，p = 6.87 × 10-3；PGS-SCZ：1.09 [1.04-1.14]，p = 8.61 × 10-4）：这些结果表明，遗传混杂因素可以解释早期使用激素避孕药与抑郁症之间的部分关联。在可能的情况下，研究人员在研究这一重要课题时，应考虑到精神疾病遗传责任可能造成的混杂因素。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Acta Psychiatrica Scandinavica 医学-精神病学

CiteScore

11.20

自引率

3.00%

发文量

135

审稿时长

6-12 weeks

期刊介绍： Acta Psychiatrica Scandinavica acts as an international forum for the dissemination of information advancing the science and practice of psychiatry. In particular we focus on communicating frontline research to clinical psychiatrists and psychiatric researchers. Acta Psychiatrica Scandinavica has traditionally been and remains a journal focusing predominantly on clinical psychiatry, but translational psychiatry is a topic of growing importance to our readers. Therefore, the journal welcomes submission of manuscripts based on both clinical- and more translational (e.g. preclinical and epidemiological) research. When preparing manuscripts based on translational studies for submission to Acta Psychiatrica Scandinavica, the authors should place emphasis on the clinical significance of the research question and the findings. Manuscripts based solely on preclinical research (e.g. animal models) are normally not considered for publication in the Journal.