Boosting serotonin in the brain: is it time to revamp the treatment of depression?

J Psychopharmacol. 2012 May;26(5):629-35. doi: 10.1177/0269881111430744. Epub 2011 Dec 8.


Abnormalities in serotonin systems are presumably linked to various psychiatric disorders including schizophrenia and depression. Medications intended for these disorders aim to either block the reuptake or the degradation of this neurotransmitter. In an alternative approach, efforts have been made to enhance serotonin levels through dietary manipulation of precursor levels with modest clinical success. In the last 30 years, there has been little improvement in the pharmaceutical management of depression, and now is the time to revisit therapeutic strategies for the treatment of this disease. Tryptophan hydroxylase (TPH) catalyzes the first and rate-limiting step in the biosynthesis of serotonin. A recently discovered isoform, TPH2, is responsible for serotonin biosynthesis in the brain. Learning how to activate this enzyme (and its polymorphic versions) may lead to a new, more selective generation of antidepressants, able to regulate the levels of serotonin in the brain with fewer side effects.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use*
  • Brain / drug effects*
  • Brain / enzymology
  • Brain / metabolism*
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / metabolism*
  • Humans
  • Protein Processing, Post-Translational / drug effects
  • Serotonin / biosynthesis*
  • Tryptophan Hydroxylase / metabolism


  • Antidepressive Agents
  • Serotonin
  • TPH2 protein, human
  • Tryptophan Hydroxylase