A human translational model based on neuroplasticity for pharmacological agents potentially effective in Treatment-Resistant Depression:focus on dopaminergic system

摘要

Major depressive disorder(MDD)is a common psychiatric condition characterized by two main symptoms,low mood and anhedonia.About 15–30%of people suffering from MDD do not respond to standard-of-care antidepressants,e.g.,the serotonin re-uptake inhibitors(SSRI),and are considered affected by Treatment-Resistant Depression(TRD).The neurobiology of this condition is presently unknown.Recent attempts of developing novel treatments for TRD have been driven by four major breakthroughs:(1)Increasing dopaminergic neurotransmission improves TRD symptoms;(2)Anhedonia occurs when central dopaminergic neurotransmission is low;(3)Enhanced neuroplasticity is critical for the action of antidepressants;(4)Ketamine shows antidepressant properties in TRD patients and triggers neuroplasticity in preclinical animal models.These breakthroughs are at the basis of a putative human translational cellular model for antidepressant agents that we are proposing in this article.The rationale is briefly described here.