Rodolpho Joice M A, Godoy Krissia F, Fragelli Bruna D L, Bianchi Jaqueline, Duarte Fernanda O, Camillo Luciana, Silva Gustavo B, Andrade Paulo H M, Prado Juliana A, Speglich Carlos, Anibal Fernanda F
Laboratory of Inflammation and Infectious Diseases, Federal University of São Carlos (UFSCar), São Carlos 13565-905, SP, Brazil.
Center for Development of Functional Materials, Federal University of São Carlos (UFSCar), São Carlos 13565-905, SP, Brazil.
Biomolecules. 2025 May 29;15(6):793. doi: 10.3390/biom15060793.
Depression and anxiety are mental health disorders that significantly impact global public health, affecting more than 280 million people with depression and 301 million with anxiety worldwide. These conditions impair individuals' ability to engage in economic and personal activities and can lead to severe outcomes, such as suicide. Current research suggests that inflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor (TNF), play crucial roles in the pathophysiology of these disorders, influencing neurotransmitters. Elevated cortisol levels, typically associated with anxiety, worsen these conditions through dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Additionally, vitamin D deficiency has been linked to reduced production of dopamine and norepinephrine, hormones involved in depressive symptoms. This study utilized the Random Forest machine learning algorithm along with cross-validation to assess the importance of various biomarkers, including IL-1β, IL-6, IL-8, TNF, cortisol, vitamin D, NT-proBNP, CK-MB, troponin, myoglobin, and C-reactive protein (CRP), in volunteers of both sexes diagnosed with mental disorders. A single sample from each of the 96 participants was analyzed, consisting of 50 women and 46 men. The results revealed sex-specific differences in biomarker relevance, with vitamin D, CRP, and D-dimer being the most predictive for depression in men, while IL-6, CRP, and vitamin D were significant in women. For anxiety, vitamin D and myoglobin were important biomarkers in men, while IL-8 and vitamin D were key in women. The methodological strategy adopted, based on the use of Random Forest and cross-validation assessment, not only confirmed the robustness of the model but also reliably identified the most important biomarkers for the outcomes studied.
抑郁症和焦虑症是严重影响全球公共卫生的心理健康障碍，全球有超过2.8亿人患有抑郁症，3.01亿人患有焦虑症。这些疾病损害了个人参与经济和个人活动的能力，并可能导致严重后果，如自杀。目前的研究表明，炎性细胞因子，如白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子（TNF），在这些疾病的病理生理学中发挥着关键作用，影响神经递质。通常与焦虑相关的皮质醇水平升高，通过下丘脑-垂体-肾上腺（HPA）轴的失调使这些疾病恶化。此外，维生素D缺乏与多巴胺和去甲肾上腺素的生成减少有关，这两种激素与抑郁症状有关。本研究利用随机森林机器学习算法以及交叉验证来评估各种生物标志物的重要性，包括IL-1β、IL-6、IL-8、TNF、皮质醇、维生素D、N末端脑钠肽前体（NT-proBNP）、肌酸激酶同工酶（CK-MB）、肌钙蛋白、肌红蛋白和C反应蛋白（CRP），在被诊断患有精神障碍的男女志愿者中。对96名参与者每人的一个样本进行了分析，其中包括50名女性和46名男性。结果揭示了生物标志物相关性的性别差异，维生素D、CRP和D-二聚体对男性抑郁症的预测性最强，而IL-6、CRP和维生素D对女性抑郁症具有显著意义。对于焦虑症，维生素D和肌红蛋白是男性的重要生物标志物，而IL-8和维生素D是女性的关键生物标志物。所采用的方法策略基于随机森林和交叉验证评估的使用，不仅证实了模型的稳健性，而且可靠地确定了所研究结果的最重要生物标志物。
