Brietzke Elisa, Stabellini Raquel, Grassi-Oliveira Rodrigo, Lafer Beny
CNS Spectr. 2011 Jul;16(7):157-68. doi: 10.1017/S1092852912000338.
An emerging body of evidence points to impairments in neuroplasticity, cell resilience, and neuronal survival as major pathophysiological mechanisms in bipolar disorder. Neuronal survival is influenced by several factors including an orchestrated action of neurotransmitters, hormones, and neurotrophins. Patients with bipolar disorder exhibit increased peripheral level of inflammatory mediators such as cytokines, mainly during acute mood episodes. These mediators interact in several pathways involved in regulation of mood and energy including hypothalamic-pituitary-adrenal axis and monoamine metabolism. Importantly, inflammatory cytokines have a potential role in controlling neuronal and glial cell loss that occurs during mood episodes, especially during mania, as they are the most powerful extracellular stimuli to apoptosis. Bipolar patients have been reported to show imbalanced peripheral production of cytokines both at the mRNA and protein levels, associated signal transduction machinery, as well as to have specific functional polymorphisms in the genes that encode these cytokines. Interestingly, lithium, valproate, and several antidepressants have demonstrated to have immunomodulatory properties. Growing evidence supports the involvement of inflammatory mechanisms in bipolar disorder, opening new paths of investigation using immunomodulatory medications. These findings can offer not only an opportunity of treating mood symptoms but also understanding and reverting neurobiological changes associated with the disorder.
越来越多的证据表明，神经可塑性、细胞弹性和神经元存活受损是双相情感障碍的主要病理生理机制。神经元的存活受多种因素影响，包括神经递质、激素和神经营养因子的协同作用。双相情感障碍患者外周炎症介质如细胞因子水平升高，主要在急性情绪发作期间。这些介质在包括下丘脑 - 垂体 - 肾上腺轴和单胺代谢在内的多个参与情绪和能量调节的途径中相互作用。重要的是，炎症细胞因子在控制情绪发作期间，尤其是躁狂期间发生的神经元和神经胶质细胞损失方面具有潜在作用，因为它们是细胞凋亡最强大的细胞外刺激因素。据报道，双相情感障碍患者在mRNA和蛋白质水平、相关信号转导机制方面外周细胞因子产生失衡，并且在编码这些细胞因子的基因中存在特定的功能多态性。有趣的是，锂盐、丙戊酸盐和几种抗抑郁药已被证明具有免疫调节特性。越来越多的证据支持炎症机制参与双相情感障碍，为使用免疫调节药物开辟了新的研究途径。这些发现不仅为治疗情绪症状提供了机会，也为理解和逆转与该疾病相关的神经生物学变化提供了可能。
