Singh Harpreet, Singh Abhishek K, Kar Sujita K, Tripathi Adarsh, Dalal Pronob K, Dikshit Madhu
Department of Psychiatry, King George's Medical University, Lucknow, Uttar Pradesh, India.
Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India.
Indian J Psychiatry. 2025 Feb;67(2):209-218. doi: 10.4103/indianjpsychiatry.indianjpsychiatry_396_23. Epub 2025 Feb 19.
Bipolar disorder (BD) is one of the most encountered disorders in psychiatric clinics. Despite extensive research and advancements in BD treatment, little is known about the disease's primary etiopathogenesis and relationship with different pathophysiological traits. The present study is aimed to evaluate the pathophysiological role of oxidative and nitrosative stress in BD patients and identify their familial aggregation.
Blood samples from healthy individuals, drug-naive symptomatic BD patients, and their first-degree relatives were obtained, and intracellular reactive oxygen/nitrogen species (ROS/RNS), total nitrites, neuronal nitric oxide synthase (nNOS) mRNA expression, myeloperoxidase (MPO) activity in polymorphonuclear neutrophils (PMNs), and serum cortisol levels were assessed.
ROS, MPO activity, total-nitrite content, nNOS expression in PMNs, and serum cortisol concentration were considerably more in BD patients than in healthy volunteers. All these variables showed a substantial correlation with the YMRS score for disease severity and the presence of one or more manic episodes. Additionally, a positive correlation was noted between the MPO activity and serum cortisol levels of BD patients and their first-degree relatives.
The results of the present study advance our knowledge about the role of oxidative and nitrosative stress in BD pathophysiology and its familial aggregation. Additionally, the study demonstrates a direct correlation between the disease severity and levels of ROS/RNS, MPO, total nitrite, and nNOS transcripts in PMNs. However, future research with larger and more diverse participant populations is required to understand these pathways for use as potential biomarkers for a deeper understanding of BD pathophysiology and to improve therapeutic strategies.
双相情感障碍（BD）是精神科诊所中最常见的疾病之一。尽管对双相情感障碍的治疗进行了广泛研究并取得了进展，但对于该疾病的主要病因发病机制以及与不同病理生理特征的关系仍知之甚少。本研究旨在评估氧化应激和亚硝化应激在双相情感障碍患者中的病理生理作用，并确定其家族聚集性。
采集健康个体、未服用药物的有症状双相情感障碍患者及其一级亲属的血样，评估细胞内活性氧/氮物种（ROS/RNS）、总亚硝酸盐、神经元型一氧化氮合酶（nNOS）mRNA表达、多形核中性粒细胞（PMN）中的髓过氧化物酶（MPO）活性以及血清皮质醇水平。
双相情感障碍患者的ROS、MPO活性、总亚硝酸盐含量、PMN中的nNOS表达以及血清皮质醇浓度均显著高于健康志愿者。所有这些变量均与疾病严重程度的杨氏躁狂量表（YMRS）评分以及一次或多次躁狂发作的存在显著相关。此外，双相情感障碍患者及其一级亲属的MPO活性与血清皮质醇水平之间存在正相关。
本研究结果增进了我们对氧化应激和亚硝化应激在双相情感障碍病理生理学中的作用及其家族聚集性的认识。此外，该研究表明疾病严重程度与PMN中的ROS/RNS、MPO、总亚硝酸盐和nNOS转录水平之间存在直接相关性。然而，需要进行更大规模和更多样化参与者群体的未来研究，以了解这些途径，将其用作潜在生物标志物，从而更深入地理解双相情感障碍的病理生理学并改善治疗策略。
