Persistent reduction in brain serotonin1A receptor binding in recovered depressed men measured by positron emission tomography with [11C]WAY-100635

Mol Psychiatry. 2004 Apr;9(4):386-92. doi: 10.1038/


Positron emission tomography (PET) studies with the selective 5-HT(1A) receptor ligand, [(11)C]WAY-100635, have indicated that the binding potential (BP) of brain 5-HT(1A) receptors is lowered in unmedicated subjects with acute major depression. However, it is unclear if these changes persist after recovery from depression. To resolve this issue, we used [(11)C]WAY-100635 in conjunction with PET imaging to compare 5-HT(1A) BP in 18 healthy controls and 14 male subjects with recurrent major depression who were clinically recovered and free of antidepressant medication. BP values, derived from a reference tissue model, were analysed by region of interest and statistical parametric mapping. Both analyses showed a widespread and substantial (17%) decrease in 5-HT(1A) receptor BP in cortical areas in the recovered depressed subjects. In contrast, 5-HT(1A) BP in the raphe nuclei did not distinguish depressed subjects from controls. Our results suggest a persistent dysfunction in cortical 5-HT(1A) BP as measured by [(11)C]WAY-100635 in recovered depressed men. Lowered 5-HT(1A) receptor binding availability could represent a trait abnormality that confers vulnerability to recurrent major depression.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antidepressive Agents / therapeutic use
  • Brain Mapping*
  • Carbon Isotopes / metabolism
  • Cerebral Cortex / diagnostic imaging*
  • Cerebral Cortex / metabolism*
  • Depressive Disorder, Major / diagnostic imaging
  • Depressive Disorder, Major / drug therapy
  • Depressive Disorder, Major / metabolism*
  • Humans
  • Male
  • Matched-Pair Analysis
  • Middle Aged
  • Piperazines / metabolism*
  • Positron-Emission Tomography
  • Pyridines / metabolism*
  • Radiopharmaceuticals
  • Raphe Nuclei / diagnostic imaging
  • Raphe Nuclei / metabolism
  • Receptor, Serotonin, 5-HT1A / metabolism*
  • Reference Values
  • Serotonin Antagonists / metabolism*


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