University of Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), Center for Neuroscience and Cell Biology (CNC), 3004-504, Coimbra, Portugal; University of Coimbra, Faculty of Medicine, 3000-548, Coimbra, Portugal.
University of Coimbra, Faculty of Pharmacy, 3000-548, Coimbra, Portugal.
Pharmacol Res. 2021 Jan;163:105325. doi: 10.1016/j.phrs.2020.105325. Epub 2020 Dec 2.
Bipolar disorder (BD) is a chronic and cyclic mental disorder, characterized by unusual mood swings between mania/hypomania and depression, raising concern in both scientific and medical communities due to its deleterious social and economic impact. Polypharmacy is the rule due to the partial effectiveness of available drugs. Disease course is often unremitting, resulting in frequent cognitive deficits over time. Despite all research efforts in identifying BD-associated molecular mechanisms, current knowledge remains limited. However, the involvement of inflammation in BD pathophysiology is increasingly consensual, with the immune system and neuroinflammation playing a key role in disease course. Evidence includes altered levels of cytokines and acute-phase proteins, pathological microglial activation, deregulation of Nrf2-Keap1 system and changes in biogenic amines neurotransmitters, whose expression is regulated by TNF-α, a pro-inflammatory cytokine highly involved in BD, pointing out inflammation as a novel and attractive therapeutic target for BD. As result, new therapeutic agents including non-steroidal anti-inflammatory drugs, N-acetylcysteine and GSK3 inhibitors have been incorporated in BD treatment. Taking into consideration the latest pre-clinical and clinical trials, in this review we discuss recent data regarding inflammation in BD, unveiling potential therapeutic approaches through direct or indirect modulation of inflammatory response.
双相情感障碍 (BD) 是一种慢性、周期性的精神障碍，其特征是躁狂/轻躁狂和抑郁之间出现异常的情绪波动，由于其对社会和经济的有害影响，引起了科学界和医学界的关注。由于现有药物的部分疗效，联合用药是常规做法。由于疾病的持续存在，随着时间的推移，认知功能缺陷经常发生。尽管在确定与 BD 相关的分子机制方面做出了所有研究努力，但目前的知识仍然有限。然而，炎症在 BD 病理生理学中的参与越来越被认同，免疫系统和神经炎症在疾病过程中起着关键作用。证据包括细胞因子和急性期蛋白水平的改变、病理性小胶质细胞激活、Nrf2-Keap1 系统的失调以及生物胺神经递质的变化，其表达受 TNF-α调控，TNF-α 是一种与 BD 高度相关的促炎细胞因子，表明炎症是 BD 的一个新的有吸引力的治疗靶点。因此，包括非甾体抗炎药、N-乙酰半胱氨酸和 GSK3 抑制剂在内的新治疗药物已被纳入 BD 治疗中。考虑到最新的临床前和临床试验，在这篇综述中，我们讨论了 BD 中炎症的最新数据，通过直接或间接调节炎症反应，揭示了潜在的治疗方法。
