School of Public Health, Health Science Center, Ningbo University, Ningbo, Zhejiang 315211, China; Zhejiang Engineering Research Center of Advanced Mass Spectrometry and Clinical Application, Ningbo University, Ningbo, Zhengjiang 315211, China.
The Affiliated Kangning Hospital, Ningbo University, Ningbo, Zhejiang 315201, China.
Ecotoxicol Environ Saf. 2024 Jul 1;279:116482. doi: 10.1016/j.ecoenv.2024.116482. Epub 2024 May 20.
Heavy metals and per- and polyfluoroalkyl substances (PFASs) have become particularly important when studying the development of depression, a common illness that severely restricts psychosocial functioning and diminishes quality of life. Therefore, the potential joint effects of heavy metal and PFAS exposure on depression, as well as the underlying mechanisms involved, were investigated by using integrated epidemiological and bioinformatic approaches in the present study. A thorough analysis of 7301 samples from the National Health and Nutrition Examination Survey (NHANES) cycles that occurred between 2005 and 2018 was performed. Single-exposure studies have shown that cadmium exposure is positively associated with depression, whereas perfluorooctanesulfonic acid (PFOS) exposure and perfluorodecanoic acid (PFDE) exposure are negatively associated with depression. Furthermore, the Bayesian kernel machine regression (BKMR) and quantile g-computation (QGcomp) models were employed to investigate the collective impact of exposure to mixed metals on depression. Cadmium emerged as the principal contributor to depression. Moreover, the addition of PFAS to the metal mixture had an antagonistic effect on depression, with PFOS having the most prominent influence. Analysis of the effects of co-exposure to cadmium and PFOS confirmed the presence of an antagonistic effect. The inflection points of cadmium and PFOS were determined to be -1.11 and 2.27, respectively. Additionally, exposure to cadmium and PFOS had the opposite effects on two crucial pathways, namely, the rap1 and calcium signaling pathways, which involve core genes related to depression such as ADORA2A, FGF2, and FGFR1. These findings have significant implications for future studies and provide new strategies for exploring the mechanisms underlying co-exposure effects.
重金属和全氟及多氟烷基物质（PFASs）在研究抑郁症的发病机制方面变得尤为重要，抑郁症是一种常见的疾病，严重限制了社会心理功能并降低了生活质量。因此，本研究采用综合流行病学和生物信息学方法，研究了重金属和 PFAS 暴露对抑郁症的潜在联合效应及其潜在机制。对 2005 年至 2018 年期间进行的国家健康和营养检查调查（NHANES）周期中的 7301 个样本进行了全面分析。单暴露研究表明，镉暴露与抑郁症呈正相关，而全氟辛烷磺酸（PFOS）暴露和全氟癸酸（PFDE）暴露与抑郁症呈负相关。此外，还采用贝叶斯核机器回归（BKMR）和分位数 g 计算（QGcomp）模型来研究混合金属暴露对抑郁症的综合影响。结果表明，镉是导致抑郁症的主要因素。此外，将 PFAS 添加到金属混合物中对抑郁症有拮抗作用，其中 PFOS 的影响最为显著。对镉和 PFOS 共同暴露的影响分析证实了拮抗作用的存在。镉和 PFOS 的拐点分别为-1.11 和 2.27。此外，镉和 PFOS 的暴露对 rap1 和钙信号通路这两个关键通路有相反的影响，这两条通路涉及与抑郁症相关的核心基因，如 ADORA2A、FGF2 和 FGFR1。这些发现对未来的研究具有重要意义，并为探索共同暴露效应的机制提供了新的策略。
