Imaging the serotonin 1A receptor using [11C]WAY100635 in healthy controls and major depression

Philos Trans R Soc Lond B Biol Sci. 2013 Feb 25;368(1615):20120004. doi: 10.1098/rstb.2012.0004. Print 2013.


As a neurotransmitter, serotonin (5-HT) is widely used throughout the brain and known to play a role in many processes including emotion and brain development. Of the 15 subtypes of 5-HT receptors, the 1A receptor (5-HT(1A)) has been implicated in depression and suicide. Using the [carbonyl-(11)C]WAY100635 ([(11)C]WAY) ligand and positron emission tomography, we have studied the 5-HT(1A) receptor, first in a group of healthy controls, then in two separate groups of subjects with major depressive disorder (MDD) (antidepressant exposed and not recently medicated), and, lastly, in a group of subjects remitted from MDD. All MDD subjects were medication-free at the time of scan. We found higher 5-HT(1A) binding potential (BP(F)) in MDD subjects not recently exposed to an antidepressant compared with controls and recently medicated MDD subjects; and higher BP(F) in subjects with the C(-1019)G promoter polymorphism. We replicated these findings in a novel cohort and reconciled our discrepant findings with other groups using alternate quantification techniques. We also reported higher BP(F) in subjects remitted from a major depressive episode than in controls. From this work, we proposed a temporal model in which 5-HT(1A) BP(F) may be a trait abnormality of MDD. To further explore the genetic components of MDD and utility of 5-HT(1A) imaging as a potential tool for biomarker or treatment response prediction, these findings should be replicated in a larger cohort using the [(11)C]CUMI-101 agonist tracer.

Publication types

  • Review

MeSH terms

  • Antidepressive Agents / pharmacology
  • Biomarkers / chemistry
  • Case-Control Studies
  • Depressive Disorder, Major / drug therapy
  • Depressive Disorder, Major / physiopathology*
  • Humans
  • Ligands
  • Piperazines / chemistry*
  • Polymorphism, Genetic
  • Positron-Emission Tomography / methods*
  • Promoter Regions, Genetic
  • Protein Binding
  • Pyridines / chemistry*
  • Receptor, Serotonin, 5-HT1A / chemistry*
  • Receptor, Serotonin, 5-HT1A / genetics


  • Antidepressive Agents
  • Biomarkers
  • Ligands
  • Piperazines
  • Pyridines
  • desmethyl-WAY 100635
  • Receptor, Serotonin, 5-HT1A