Altered serotonin 1A binding in major depression: a [carbonyl-C-11]WAY100635 positron emission tomography study

Biol Psychiatry. 2006 Jan 15;59(2):106-13. doi: 10.1016/j.biopsych.2005.06.016. Epub 2005 Sep 9.


Background: Serotonin 1A receptors (5-HT(1A)) are implicated in the pathophysiology of major depressive disorder (MDD) and in the action of selective serotonin reuptake inhibitors (SSRI). SSRI desensitize 5-HT(1A) and down-regulate 5-HT transporters (5-HTT) with the latter persisting for weeks after discontinuation of SSRI. MDD subjects are more likely to be homozygous for the functional 5-HT(1A) G(-1019) allele of the promoter polymorphism and are postulated to have higher 5-HT(1A) than healthy volunteers (controls). We measure 5-HT(1A) in MDD, assess the effects of antidepressant exposure (AE), and examine the role of the C(-1019)G polymorphism.

Methods: Genotyped and determined 5-HT(1A) binding potential (BP) by positron emission tomography (PET) using [carbonyl-C-11]-WAY-100635 in 28 medication-free MDD subjects during a current major depressive episode and 43 controls.

Results: No difference in BP between controls and MDD subjects (p = .235). There was a difference in BP comparing the controls, antidepressant naive (AN) MDD subjects, and subjects with AE across all regions (p = .013). Post hoc testing reveals higher BP in AN compared to controls (p = .008) and to AE (p = .007). The GG genotype is overrepresented in MDD subjects (p = .059), and BP appears higher with the G allele.

Conclusions: AN have higher 5-HT(1A) than controls and AE suggesting a model of depression characterized by an over expression of autoinhibitory somatodendritic 5-HT(1A) receptors, perhaps due to the higher expressing G allele, that may result in reduced terminal field 5-HT release. AE appears to have long-term effects on 5-HT(1A).

Publication types

  • Comparative Study
  • Controlled Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antidepressive Agents / therapeutic use
  • Carbon Radioisotopes / metabolism
  • Depressive Disorder, Major / diagnostic imaging
  • Depressive Disorder, Major / drug therapy
  • Depressive Disorder, Major / genetics*
  • Depressive Disorder, Major / metabolism*
  • Female
  • Humans
  • Male
  • Piperazines / metabolism
  • Polymorphism, Genetic
  • Positron-Emission Tomography
  • Promoter Regions, Genetic / genetics
  • Pyridines / metabolism
  • Receptor, Serotonin, 5-HT1A / drug effects
  • Receptor, Serotonin, 5-HT1A / genetics*
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Reference Values
  • Serotonin Antagonists / metabolism


  • Antidepressive Agents
  • Carbon Radioisotopes
  • Piperazines
  • Pyridines
  • Serotonin Antagonists
  • Receptor, Serotonin, 5-HT1A
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide