The 5-HT deficiency theory of depression: perspectives from a naturalistic 5-HT deficiency model, the tryptophan hydroxylase 2Arg439His knockin mouse.

Journal Article (Review)

A decreased level of brain 5-hydroxytryptamine (5-HT) has been theorized to be a core pathogenic factor in depression for half a century. The theory arose from clinical observations that drugs enhancing extracellular levels of 5-HT (5-HT(Ext)) have antidepressant effects in many patients. However, whether such drugs indeed correct a primary deficit remains unresolved. Still, a number of anomalies in putative biomarkers of central 5-HT function have been repeatedly reported in depression patients over the past 40 years, collectively indicating that 5-HT deficiency could be present in depression, particularly in severely ill and/or suicidal patients. This body of literature on putative 5-HT biomarker anomalies and depression has recently been corroborated by data demonstrating that such anomalies indeed occur consequent to severely reduced 5-HT(Ext) levels in a mouse model of naturalistic 5-HT deficiency, the tryptophan hydroxylase 2 His(439) knockin (Tph2KI) mouse. In this review, we will critically assess the evidence for 5-HT deficiency in depression and the possible role of polymorphisms in the Tph2 gene as a causal factor in 5-HT deficiency, the latter investigated from a clinical as well as preclinical angle.

Full Text

Duke Authors

Cited Authors

  • Jacobsen, JPR; Medvedev, IO; Caron, MG

Published Date

  • September 5, 2012

Published In

Volume / Issue

  • 367 / 1601

Start / End Page

  • 2444 - 2459

PubMed ID

  • 22826344

Electronic International Standard Serial Number (EISSN)

  • 1471-2970

Digital Object Identifier (DOI)

  • 10.1098/rstb.2012.0109

Language

  • eng

Conference Location

  • England