双相情感障碍中情绪障碍的多基因风险与应激性生活事件之间的相互作用。

Interplay between polygenic risk for mood disorders and stressful life events in bipolar disorder.

作者信息

Hosang Georgina M, Shakoor Sania, King Nicole, Sanches Marcos, Vincent John B, Kennedy James L, McGuffin Peter, Keers Robert, Zai Clement C

机构信息

Centre for Psychiatry & Mental Health, Wolfson Institute of Population Health, Barts and the London Faulty of Medicine and Dentistry, Queen Mary, University of London, UK.

出版信息

J Affect Disord. 2024 Apr 1;350:565-572. doi: 10.1016/j.jad.2024.01.167. Epub 2024 Jan 19.

DOI:10.1016/j.jad.2024.01.167

PMID:38246285

Abstract

BACKGROUND

Although genetic and environmental factors are involved in the aetiology of bipolar disorder [BD], studies focused on their interplay are lacking. The current investigation examines interactions and correlations between polygenic risk scores [PRS] for BD and major depressive disorder [MDD] with stressful life events [SLEs] in liability for BD.

METHODS

This study used data from 1715 participants (862 bipolar cases and 853 controls) taken from UK and Canadian samples. The List of Threatening Experiences Questionnaire recorded SLEs that occurred 6 months before interview for controls and 6 months prior to the first (Canadian sample) and worst (UK sample) depressive and manic episodes for bipolar cases. PRS-BD and PRS-MDD were calculated from the Psychiatric Genomics Consortium.

RESULTS

For the worst depressive episode, the PRS-MDD was significantly correlated with total number of SLEs (β = 0.13, 95 % CI:0.04-0.22, p = 0.003) and dependent SLEs (β = 0.09, 95 % CI:0.02-0.16, p = 0.007). After correction for multiple testing nominally significant correlations were detected for PRS-BD with total number of SLEs (β = 0.11, 95 % CI:0.02-0.20, p = 0.015) and dependent SLEs (β = 0.08, 95 % CI:0.01-0.15, p = 0.019). Among bipolar cases, these associations were slightly stronger but were only of nominal significance for total number of SLEs (PRS-MDD: β = 0.19, 95 % CI:0.04-0.35, p = 0.015; PRS-BD: β = 0.16, 95 % CI:0.01-0.32, p = 0.042) and dependent SLEs (PRS-MDD: β = 0.14, 95 % CI:0.03-0.26, p = 0.015; PRS-BD: β = 0.12, 95 % CI:0.004-0.24, p = 0.043). No other significant gene-environment correlations or interactions were found.

LIMITATIONS

Use of a larger sample size would be beneficial.

CONCLUSIONS

The relationship between SLEs and genetic risk for mood disorders may be best explained through correlations rather than interactions.

摘要

背景

尽管遗传和环境因素都与双相情感障碍（BD）的病因有关，但缺乏关注它们相互作用的研究。本研究调查BD和重度抑郁症（MDD）的多基因风险评分（PRS）与BD易感性中应激性生活事件（SLE）之间的相互作用和相关性。

方法

本研究使用了来自英国和加拿大样本的1715名参与者（862例双相情感障碍患者和853名对照）的数据。威胁性经历问卷记录了对照组在访谈前6个月以及双相情感障碍患者首次（加拿大样本）和最严重（英国样本）抑郁和躁狂发作前6个月发生的SLE。PRS-BD和PRS-MDD由精神疾病基因组学联盟计算得出。

结果

对于最严重的抑郁发作，PRS-MDD与SLE总数（β = 0.13，95%CI：0.04 - 0.22，p = 0.003）和依赖性SLE（β = 0.09，95%CI：0.02 - 0.16，p = 0.007）显著相关。在进行多重检验校正后，检测到PRS-BD与SLE总数（β = 0.11，95%CI：0.02 - 0.20，p = 0.015）和依赖性SLE（β = 0.08，95%CI：0.01 - 0.15，p = 0.019）存在名义上的显著相关性。在双相情感障碍患者中，这些关联稍强，但仅在SLE总数（PRS-MDD：β = 0.19，95%CI：0.04 - 0.35，p = 0.015；PRS-BD：β = 0.16，95%CI：0.01 - 0.32，p = 0.042）和依赖性SLE（PRS-MDD：β = 0.14，95%CI：0.03 - 0.26，p = 0.015；PRS-BD：β = 0.12，95%CI：0.004 - 0.24，p = 0.043）方面具有名义上的显著性。未发现其他显著的基因 - 环境相关性或相互作用。