The double edged sword of neural plasticity: Increasing serotonin levels leads to both greater vulnerability to depression and improved capacity to recover
The double edged sword of neural plasticity: Increasing serotonin levels leads to both greater vulnerability to depression and improved capacity to recover
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DOI：
10.1016/j.psyneuen.2010.08.011
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发表时间：
2011-04-01
影响因子：
3.7
通讯作者：
Branchi, Igor
中科院分区：
文献类型：
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作者：
Branchi, Igor
重度抑郁症是一种慢性、复发性和可能危及生命的疾病，影响全球高达10%的人口。药理学和遗传学研究强调了多巴胺能系统是该疾病的关键参与者。然而，尽管旨在促进5-羟色胺传输的药物代表了抑郁症的第一线治疗，但该系统的作用仍然难以捉摸。在这里，我提出了一个新的理论框架，无向易感性变化模型，可能占实验和临床结果有关的作用，这种神经递质在抑郁症。由于个体根据环境改变其生理和行为的能力取决于神经可塑性，而神经可塑性又由血清素控制，因此我认为血清素水平的变化会影响对环境的敏感性。因此，对变化的非定向易感性模型预测，例如通过选择性5-羟色胺再摄取抑制剂（SSRI）施用诱导的5-羟色胺水平的增加不会影响情绪本身，但是-作为催化剂-增强神经可塑性，从而增强环境对情绪的影响。然而，由于环境可能是有利的或不利的，其影响可能是有益的或有害的。因此，增强5-羟色胺系统可以增加发展精神病理学和从精神病理学中恢复的可能性。这个模型，一方面，提出了临床研究中描述的有限SSRI疗效的解释，并允许调和明显矛盾的数据;另一方面，它将神经可塑性描述为一把双刃剑，根据环境的质量，可能会产生积极或消极的后果。(C)2010爱思唯尔有限公司版权所有。
Major depression is a chronic, recurring and potentially life-threatening illness that affects up to 10% of the population worldwide. Pharmacological and genetic studies highlight the serotonergic system as being a key player in the disorder. However, despite drugs designed to boost serotonin transmission represent the first line of therapy for depression, the role of this system still remains elusive. Here, I propose a new theoretical framework, the undirected susceptibility to change model, potentially accounting for the experimental and clinical results concerning the role of this neurotransmitter in depression. Since the capacity of the individual to change its physiology and behavior according to the environment is dependent on neural plasticity which, in turn, is controlled by serotonin, I assume that changes in the levels of serotonin affect the sensitivity to the environment. Consequently, the undirected susceptibility to change model predicts that an increase of serotonin levels, for instance induced through selective serotonin reuptake inhibitor (SSRI) administration, does not affect mood per se, but - acting as a catalyzer - enhances neural plasticity and, thus, the effects of the environment on mood. However, since the environment can be either supportive or adverse, its effects can be beneficial or detrimental. Therefore enhancing the serotonin system can increase the likelihood both of developing the psychopathology and recovering from it. This model, on the one hand, suggests an explanation for the limited SSRI efficacy described in clinical studies and allows apparently contradictory data to be reconciled; on the other, it describes neural plasticity as a double edged sword that, according to the quality of the environment, may have either positive or negative consequences. (C) 2010 Elsevier Ltd. All rights reserved.