Charney Dennis S, Dejesus Georgette, Manji Husseini K
National Institute of Mental Health, Bethesda, Md, USA.
Dialogues Clin Neurosci. 2004 Jun;6(2):217-25. doi: 10.31887/DCNS.2004.6.2/dcharney.
Recent advances in the identification of the neural circuits, neurochemicals, and signal transduction mechanisms involved in the pathophysiology and treatment of mood disorders have led to much progress toward understanding the roles of genetic factors and psychosocial stressors. The monoaminergic neurotransmitter systems have received the most attention, partly because of the observation that effective antidepressant drugs exert their primary biochemical effects by regulating intrasynaptic concentrations of serotonin and norepinephrine. Furthermore, the monoaminergic systems are extensively distributed throughout the network of limbic, striatal, and prefrontal cortical neuronal circuits thought to support the behavioral and visceral manifestations of mood disorders. Increasing numbers of neuroimaging, neuropathological, and biochemical studies indicate impairments in cellular plasticity and resilience in patients who suffer from severe, recurrent mood disorders. In this paper, we describe studies identifying possible structural, functional, and cellular abnormalities associated with depressive disorders, which are potentially the cellular underpinnings of these diseases. We suggest that drugs designed to enhance cellular plasticity and resilience, and attenuate the activity of maladaptive stress-responsive systems, may be useful for the treatment of severe mood disorders.
在情绪障碍的病理生理学和治疗中涉及的神经回路、神经化学物质及信号转导机制的识别方面，最近取得的进展已在理解遗传因素和心理社会应激源的作用上带来了很大进步。单胺能神经递质系统受到了最多关注，部分原因是观察到有效的抗抑郁药物通过调节突触内血清素和去甲肾上腺素的浓度发挥其主要生化作用。此外，单胺能系统广泛分布于整个边缘系统、纹状体和前额叶皮质神经元回路网络，这些回路被认为支持情绪障碍的行为和内脏表现。越来越多的神经影像学、神经病理学和生化研究表明，患有严重复发性情绪障碍的患者存在细胞可塑性和恢复力受损的情况。在本文中，我们描述了确定与抑郁症相关的可能的结构、功能和细胞异常的研究，这些异常可能是这些疾病的细胞基础。我们认为，旨在增强细胞可塑性和恢复力并减弱适应不良应激反应系统活性的药物，可能对治疗严重情绪障碍有用。
