From Serotonin to Neuroplasticity: Evolvement of Theories for Major Depressive Disorder

Abstract

The serotonin (5-HT) hypothesis of depression has played an important role in the history of psychiatry, yet it has also been criticized for the delayed onset and inadequate efficacy of selective serotonin reuptake inhibitors (SSRIs). With evolvement of neuroscience, the neuroplasticity hypothesis of major depressive disorder (MDD) has been proposed and may provide a better framework for clarification the pathogenesis of MDD and antidepressant efficacy. In this article, we first summarized the evidence challenging the monoamine hypothesis and proposed that the antidepressant efficacy of SSRIs is not derived from elevated monoamine (5-HT, noradrenaline (NE), or dopamine (DA)) concentration or monoamine neurotransmission. Second, we reviewed the role of stress in the pathogenesis of MDD and gave a brief introduction to the neuroplasticity hypothesis of MDD. Third, we explored the possible mechanisms underlying the antidepressant efficacy of typical antidepressants in the context of neuroplasticity theory. Fourth, we tried to provide an explanatory framework for the significant difference in onset of efficacy between typical antidepressants and ketamine. Finally, we provided a brief summarization about this review article and some perspectives for future studies.

The development and tendency of depression researches: Viewed from the microbiota-gut-brain axis

“…单胺类神经递质缺乏假说认为, 幸福 和快乐等积极情绪情感离不开单胺类神经递质(如 5-HT和DA), 抑郁是由于脑内单胺类神经递质缺乏 引起, 而增加这些神经递质水平, 就能产生抗抑郁效 果 [47,49] . 但SSRIs大都起效慢, 只对一部分患者有效, 提示抑郁还涉及其他机制 [12] . 随后的研究发现, 抑 郁患者的其他神经递质可能也发生了改变, Glu能系 统和乙酰胆碱能系统过于兴奋, 而GABA能系统受到 抑制, 各个神经递质系统相互影响, 这些研究对于开 发新的抑郁症治疗方法具有重要意义 [48,50,51] .…”

“…现代生物学认为, 抑郁症不仅是一种心理疾病, 更是一种生理疾病. 抑郁症具有明显的生物学因素, 患者大脑发生了重要改变, 如脑内神经递质失衡、神 经生长受损、神经可塑性降低、神经环路异常 [12,13] .…”

Chronic pain, depression and cognitive impairment: a close relationship

“…Длительный прием антидепрессантов способствует адаптивной нейропластичности несколькими путями. Во-первых, увеличение моноаминовых нейромедиаторов и их действие на постсинаптические рецепторы приводят к активации аденилатциклазы, превращению аденозинтрифосфата в циклический аденозинмонофосфат и активации CRE-связывающего белка [63]. В результате происходит экспрессия многих белков, обеспечивающих нейропластичность гиппокампа, таких как BDNF и GluR1-субъединиц AMPA-рецепторов.…”

Flotillin‐1 interacts with the serotonin transporter and modulates chronic corticosterone response

“…Indeed, aside from the aforementioned studies which support an involvement of the serotonergic system in MDD pathophysiology, there have been numerous publications reporting conflicting evidence (reviewed in References [13][14][15] ) as well as alternative hypotheses. [16][17][18] Hence, focusing on the involvement of the serotonergic system in general, and SERT in particular, may therefore be seen as a particularly dogmatic approach to understanding MDD. However, strong evidence in the literature does indicate that this monoamine system is likely to be involved in the pathophysiology of depression, at least in a subpopulation of patients and further in-depth analyses are therefore warranted.…”