Does central nervous system serotonin (5-HT) activity have a role in the pathophysiology of major depressive disorder (clinical depression)?

Updated: Mar 28, 2019
  • Author: Jerry L Halverson, MD; Chief Editor: David Bienenfeld, MD  more...
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Answer

The role of CNS 5-HT activity in the pathophysiology of major depressive disorder is suggested by the therapeutic efficacy of selective serotonin reuptake inhibitors (SSRIs). In addition, studies have shown that an acute, transient relapse of depressive symptoms can be produced in research subjects in remission using tryptophan depletion, which causes a temporary reduction in CNS 5-HT levels. However, the effect of SSRIs on 5HT reuptake is immediate, but the antidepressant effect requires exposure of several weeks' duration. Also, some antidepressants have no effect on 5HT (eg, desipramine), and the antidepressant tianeptine enhances 5HT uptake. All this, together with preclinical research findings, implies a role for neuronal receptor regulation, intracellular signaling, and gene expression over time, in addition to enhanced neurotransmitter availability.


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