Perspective Exploring Novel Associations of IL-18 Levels as a Mediator of the Causal Links between Major Depression and Reproductive Health

IF 4.7 2区医学 Q1 PSYCHIATRY

Depression and Anxiety Pub Date : 2024-08-05 DOI:10.1155/2024/9234876

Mengying Li, Kaibo Sun, Yunyun Mei, Keyan Liu, Lei Chen, Yihong Guo

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Abstract

This research has suggested a link between major depressive disorder (MDD) and infertility, with interleukin-18 (IL-18) being proposed as a potential mediator due to its connections to both conditions. A Mendelian randomization (MR) approach was utilized in this study, which drew on genetic data from 500,199 European participants studied for MDD, along with additional IL-18 and reproductive health data from the FinnGen consortium and GWAS datasets. Single nucleotide polymorphisms were employed as instrumental variables to examine the causal relationships between MDD, genetically predicted IL-18 levels, and infertility. In our study, bidirectional MR analysis revealed a significant inverse causal relationship between MDD and genetically predicted IL-18 levels, with a higher genetic predisposition to MDD, correlating with reduced IL-18 levels (β: −0.40; 95% confidence interval (CI): −0.69 to −0.11; P = 7.09 × 10⁻³). Additionally, MDD is found to significantly increase the risk of female infertility. Notably, genetically predicted IL-18 levels demonstrated a protective effect against female infertility (odds ratio (OR): 0.92; 95% CI: 0.86–0.98; P = 1.17 × 10⁻²). Mediation analysis indicated that genetically predicted IL-18 levels partially mediated the impact of MDD on female infertility associated with cervical, vaginal, other or unspecified origin, accounting for up to 14.61% of this effect. No evidence of pleiotropy or heterogeneity was detected. The role of genetic predispositions to MDD in influencing genetically predicted IL-18 levels, and subsequently, female infertility, was highlighted by our study, offering insights into the complex interplay between mental health and reproductive biology. These findings contribute to a deeper understanding of the genetic and molecular pathways influencing these conditions, suggesting new directions for research and potential therapeutic interventions.

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视角探索 IL-18 水平作为重度抑郁症与生殖健康之间因果关系中介的新关联

这项研究表明，重度抑郁障碍（MDD）与不孕不育之间存在联系，而白细胞介素-18（IL-18）由于与这两种病症都有关联，因此被认为是潜在的中介因子。这项研究采用了孟德尔随机化（MR）方法，利用了来自500199名欧洲重度抑郁症患者的遗传数据，以及来自FinnGen联盟和GWAS数据集的其他IL-18和生殖健康数据。单核苷酸多态性被用作工具变量来研究 MDD、基因预测的 IL-18 水平和不育之间的因果关系。在我们的研究中，双向 MR 分析显示 MDD 与遗传预测 IL-18 水平之间存在显著的反向因果关系，MDD 遗传易感性越高，IL-18 水平越低（β：-0.40；95% 置信区间 (CI)：-0.69至-0.11；P = 7.09 × 10-3）。此外，研究还发现 MDD 会显著增加女性不孕的风险。值得注意的是，遗传预测的IL-18水平对女性不孕具有保护作用（几率比（OR）：0.92；95% CI：0.86-0.98；P = 1.17 × 10-2）。中介分析表明，基因预测的IL-18水平部分中介了MDD对宫颈、阴道、其他或不明原因的女性不孕症的影响，占该影响的14.61%。没有发现多效性或异质性的证据。我们的研究强调了MDD遗传倾向在影响基因预测的IL-18水平，进而影响女性不孕症方面的作用，为心理健康与生殖生物学之间复杂的相互作用提供了见解。这些发现有助于加深对影响这些疾病的遗传和分子途径的理解，为研究和潜在的治疗干预提出了新的方向。

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来源期刊

Depression and Anxiety 医学-精神病学

CiteScore

15.00

自引率

1.40%

发文量

审稿时长

4-8 weeks

期刊介绍： Depression and Anxiety is a scientific journal that focuses on the study of mood and anxiety disorders, as well as related phenomena in humans. The journal is dedicated to publishing high-quality research and review articles that contribute to the understanding and treatment of these conditions. The journal places a particular emphasis on articles that contribute to the clinical evaluation and care of individuals affected by mood and anxiety disorders. It prioritizes the publication of treatment-related research and review papers, as well as those that present novel findings that can directly impact clinical practice. The journal's goal is to advance the field by disseminating knowledge that can lead to better diagnosis, treatment, and management of these disorders, ultimately improving the quality of life for those who suffer from them.