Serotonin has traditionally been identified as the main culprit in depression. Simplistic neurotransmitter diagrams portray serotonin as a pool that gets depleted and needs to be refilled. Serotonin plays a role, but the brain is a complex system and there are more factors involved. In fact, some research indicates that chronic stress leads to brain injury, which is exhibited in symptoms of depression.
With research showing that ketamine is a rapid and effective antidepressant through its induction of synaptogenesis, the process of synapse formation is gaining more attention in the treatment of depression. Changing the neurobiological and neurochemical milieu beyond serotonin offers additional promising methods of treating depression. Targeting the mTOR pathway to accelerate synapse formation may even offer the possibility of developing a depression cure.
References:
A neurotrophic hypothesis of depression: role of synaptogenesis in the actions of NMDA receptor antagonists. (Link)
Imipramine treatment increases the number of hippocampal synapses and neurons in a genetic animal model of depression. (Link)
mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. (Link)
Remodeling of axo-spinous synapses in the pathophysiology and treatment of depression. (Link)
Signaling pathways underlying the pathophysiology and treatment of depression: novel mechanisms for rapid-acting agents. (Link)
Signaling pathways underlying the rapid antidepressant actions of ketamine. (Link)
Synaptic dysfunction in depression: potential therapeutic targets. (Link)
The roles of BDNF in the pathophysiology of major depression and in antidepressant treatment. (Link)
