Send to

Choose Destination
Front Cell Neurosci. 2017 Sep 28;11:305. doi: 10.3389/fncel.2017.00305. eCollection 2017.

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

Author information

Key Laboratory of Psychiatry and Mental Health of Hunan Province, Mental Health Institute, The Second Xiangya Hospital of Central South University, National Clinical Research Center for Mental Disorder, National Technology Institute of Psychiatry, Changsha, China.


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.


antidepressant efficacy; final common pathway; major depressive disorder; neuroplasticity; serotonin

Supplemental Content

Full text links

Icon for Frontiers Media SA Icon for PubMed Central
Loading ...
Support Center