Souama Camille, Lamers Femke, Milaneschi Yuri, Jansen Rick, Vinkers Christiaan H, Giltay Erik J, Dunlop Boadie W, Kaddurah-Daouk Rima, Penninx Brenda W J H
Department of Psychiatry, Amsterdam UMC Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Amsterdam Public Health, Mental Health Program, Amsterdam, the Netherlands.
Department of Psychiatry, Amsterdam UMC Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; Amsterdam Public Health, Mental Health Program, Amsterdam, the Netherlands.
Biol Psychiatry. 2025 Apr 4. doi: 10.1016/j.biopsych.2025.03.018.
Although childhood trauma is an important risk factor for various diseases, the underlying biological mechanisms remain insufficiently understood. To deepen this understanding, we investigated the wide-spectrum metabolomic signature of childhood trauma exposure in a large adult cohort.
Baseline and 6-year follow-up data from NESDA (Netherlands Study of Depression and Anxiety) were used (N = 2902, N = 4800). Childhood trauma exposure was retrospectively assessed with the Childhood Trauma Interview. Plasma metabolite levels were measured with the Metabolon mass spectrometry-based untargeted metabolomics platform at both time points. Mixed-effect models were used to evaluate the metabolomic associations of childhood trauma while controlling for sociodemographic, lifestyle, health-related, and technical covariates. We examined the overlap between the metabolomic profiles of childhood trauma and depression. External replication was tested in 308 additional participants.
Childhood trauma was associated in a dose-response manner with 18 metabolites. Upregulated metabolites were nominally enriched with compounds involved in fatty acid and branched-chain amino acid metabolism (p = 3.91 × 10, false discovery rate-corrected q [q] > .05) while downregulated metabolites were nominally enriched with corticosteroids (p = 2.24 × 10, q > .05). Six of the 18 metabolites were linked to childhood trauma but not depression. Findings were partially replicated using an alternative measure for childhood trauma (effect size correlation r = 0.94) and an external sample (r = 0.54).
Childhood trauma was linked in a dose-response manner to a biological signature encompassing a wide array of metabolites. Dysregulations were observed in amino acid and fatty acid metabolism as well as hypothalamic-pituitary-adrenal axis function. Future studies should corroborate these findings and develop early-intervention strategies that target trauma-related biological mechanisms to prevent cardiometabolic and psychiatric diseases.
尽管童年创伤是多种疾病的重要风险因素，但其潜在的生物学机制仍未得到充分理解。为加深对此的理解，我们在一个大型成年队列中研究了童年创伤暴露的广谱代谢组学特征。
使用了荷兰抑郁与焦虑研究（NESDA）的基线和6年随访数据（N = 2902，N = 4800）。通过童年创伤访谈对童年创伤暴露进行回顾性评估。在两个时间点均使用基于Metabolon质谱的非靶向代谢组学平台测量血浆代谢物水平。使用混合效应模型评估童年创伤的代谢组学关联，同时控制社会人口统计学、生活方式、健康相关和技术协变量。我们检查了童年创伤和抑郁症的代谢组学特征之间的重叠。在另外308名参与者中进行了外部验证。
童年创伤与18种代谢物呈剂量反应关系。上调的代谢物在名义上富含参与脂肪酸和支链氨基酸代谢的化合物（p = 3.91×10，错误发现率校正后的q [q] > 0.05），而下调的代谢物在名义上富含皮质类固醇（p = 2.24×10，q > 0.05）。18种代谢物中的6种与童年创伤有关，但与抑郁症无关。使用童年创伤的替代测量方法（效应大小相关性r = 0.94）和外部样本（r = 0.54）部分重复了研究结果。
童年创伤与包含多种代谢物的生物学特征呈剂量反应关系。在氨基酸和脂肪酸代谢以及下丘脑 - 垂体 - 肾上腺轴功能中观察到了失调。未来的研究应证实这些发现，并制定针对创伤相关生物学机制的早期干预策略，以预防心脏代谢和精神疾病。
