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双相情感障碍的新药理学干预措施

New Pharmacological Interventions in Bipolar Disorder.

作者信息

Juruena Mario F, Jelen Luke A, Young Allan H, Cleare Anthony J

机构信息

Centre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

出版信息

Curr Top Behav Neurosci. 2021;48:303-324. doi: 10.1007/7854_2020_181.

Abstract

The biological bases of bipolar disorder include aspects related, among others, to neurohormonal pathways, neurotransmission, signal transduction, regulation of gene expression, oxidative stress, neuroplasticity, and changes in the immune system. There is still a gap in understanding its complex neurobiology and, consequently, developing new treatments. Multiple factors probably interact in this complex equation of pathophysiology of bipolar disorder, such as genetic, biochemical, psychosocial, and environmental stress events, correlating with the development and severity of the bipolar disorder. These mechanisms can interact to exacerbate inflammation, impair neurogenesis, and increase oxidative stress damage, cellular mitochondrial dysfunction, changes in neurotrophins and in epigenetic mechanisms, neuroendocrine dysfunction, activation of neuronal death pathways, and dysfunction in neurotransmission systems. In this review, we explore the up-to-date knowledge of the neurobiological underpinnings of bipolar disorders. The difficulty in developing new drugs for bipolar disorder is very much associated with the lack of knowledge about the precise pathophysiology of this disorder. Pharmacological treatment for bipolar patients is vital; to progress to effective medications, it is essential to understand the neurobiology in bipolar patients better and identify novel therapeutic targets.

摘要

双相情感障碍的生物学基础包括多个方面,其中涉及神经激素途径、神经传递、信号转导、基因表达调控、氧化应激、神经可塑性以及免疫系统的变化。在理解其复杂的神经生物学以及因此开发新的治疗方法方面,仍然存在差距。在双相情感障碍病理生理学的这一复杂等式中,多种因素可能相互作用,例如遗传、生化、心理社会和环境应激事件,这些与双相情感障碍的发生和严重程度相关。这些机制可以相互作用,加剧炎症、损害神经发生、增加氧化应激损伤、细胞线粒体功能障碍、神经营养因子和表观遗传机制的变化、神经内分泌功能障碍、神经元死亡途径的激活以及神经传递系统的功能障碍。在本综述中,我们探讨双相情感障碍神经生物学基础的最新知识。开发双相情感障碍新药的困难与对该疾病精确病理生理学的了解不足密切相关。双相情感障碍患者的药物治疗至关重要;为了开发出有效的药物,必须更好地了解双相情感障碍患者的神经生物学并确定新的治疗靶点。

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