Somani Aditya, Singh Abhishek Kumar, Gupta Bandna, Nagarkoti Sheela, Dalal Pronob Kumar, Dikshit Madhu
Department of Psychiatry, King George's Medical University, Lucknow 226003, India.
Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
Brain Sci. 2022 Jan 21;12(2):144. doi: 10.3390/brainsci12020144.
The role of increased oxidative stress and alterations to the nitric oxide (NO) pathway have been implicated in major depressive disorder (MDD). The two pathways interact closely with each other but have not been studied simultaneously in MDD. This study aimed to assess and compare the levels of oxidative and nitrosative stress in the neutrophils (PMNs) of drug-naive MDD patients and their first-degree relatives.
29 drug-naive MDD patients and 27 healthy first-degree relatives and healthy controls aged 18-45 years were included in this study. An assessment of the levels of reactive oxygen species (ROS), nitrites, neuronal NO synthase (nNOS), and myeloperoxidase in PMNs, and cortisol in serum was carried out.
Compared to healthy controls, the generation of free radicals, myeloperoxidase activity, and nNOS mRNA expression in PMNs, and cortisol level in serum were significantly higher in drug-naive depression patients. Indeed, increased levels of myeloperoxidase and serum cortisol were also noted in first-degree relatives. The total nitrite content in the PMNs and plasma however was significantly lower in both patients and first-degree relatives. Interestingly, a positive correlation was established in the ROS levels in the PMNs, plasma and neutrophil nitrite, and the serum cortisol level between MDD patients and their first-degree relatives.
The results of this study contribute towards a better understanding of the familial association of depressive disorder, and demonstrate for the first time that neutrophil ROS/RNS, plasma nitrite, and serum cortisol levels are positively correlated between MDD patients and their first-degree relatives. However, further studies in larger, more diverse samples are needed to extend these pathways as potential biomarkers to identify persons at high risk for psychopathology at an early stage.
氧化应激增加和一氧化氮（NO）途径改变在重度抑郁症（MDD）中起作用。这两条途径相互密切作用，但尚未在MDD中同时进行研究。本研究旨在评估和比较未服用过药物的MDD患者及其一级亲属中性粒细胞（PMN）中的氧化应激和亚硝化应激水平。
本研究纳入了29名未服用过药物的MDD患者、27名健康一级亲属以及18至45岁的健康对照者。对PMN中活性氧（ROS）、亚硝酸盐、神经元型一氧化氮合酶（nNOS）和髓过氧化物酶水平以及血清中皮质醇水平进行了评估。
与健康对照相比，未服用过药物的抑郁症患者PMN中自由基生成、髓过氧化物酶活性和nNOS mRNA表达以及血清皮质醇水平显著更高。事实上，在一级亲属中也观察到髓过氧化物酶和血清皮质醇水平升高。然而，患者及其一级亲属的PMN和血浆中亚硝酸盐总含量均显著较低。有趣的是，MDD患者及其一级亲属的PMN中ROS水平、血浆和中性粒细胞亚硝酸盐以及血清皮质醇水平之间建立了正相关。
本研究结果有助于更好地理解抑郁症的家族关联，并首次证明MDD患者及其一级亲属之间中性粒细胞ROS/RNS、血浆亚硝酸盐和血清皮质醇水平呈正相关。然而，需要在更大、更多样化的样本中进行进一步研究，以扩展这些途径作为潜在生物标志物，以便在早期识别精神病理学高危人群。
