Brain serotonin 5-HT(1A) receptor binding in schizophrenia measured by positron emission tomography and [11C]WAY-100635

Arch Gen Psychiatry. 2002 Jun;59(6):514-20. doi: 10.1001/archpsyc.59.6.514.


Background: Results of postmortem studies show an elevation in serotonin-1A (5-hydroxytryptamine-1A [5-HT(1A)]) receptor density in the prefrontal and temporal cortices of patients with schizophrenia. This study examined 5-HT(1A) receptors in vivo in patients with schizophrenia using positron emission tomography and [carbonyl-(11)C]-N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexane carboxamide ([(11)C]WAY-100635).

Methods: The 5-HT(1A) binding potential of 14 antipsychotic drug-naïve patients with a DSM-IV diagnosis of schizophrenia was compared with that of 14 age-matched healthy controls. Positron emission tomography data were analyzed using 9 cortical regions of interest, which were delineated on a coregistered magnetic resonance image and transferred to the positron emission tomographic image, with the cerebellum as the reference region for a simplified reference tissue model. We also performed a voxel-wise comparison using statistical parametric mapping.

Results: The region of interest-based analysis revealed a significant mean +/- SD cortical 5-HT(1A) receptor binding potential increase of 7.1% +/- 6.4% in patients with schizophrenia (F = 2.975; P =.02); local differences were +20% in the left medial temporal cortex (F = 9.339;P =.005) and +13% in the right medio temporal cortex (F = 4.453; P =.045). There were no significant differences in regional tracer delivery or cerebellar [(11)C]WAY-100635 uptake. The voxel-based analysis also confirmed a group difference in the left medial temporal cortex.

Conclusions: The biological significance of elevated 5-HT(1A) receptor density in schizophrenia remains unclear. Given the location of 5-HT(1A) receptors on pyramidal cells, this elevation may reflect an abnormal glutamatergic network. Our finding needs to be viewed in light of preclinical evidence supporting a role for 5-HT(1A) receptors in mediating antipsychotic action and extrapyramidal adverse effects of drugs.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Brain Chemistry
  • Cerebellum / chemistry
  • Cerebellum / metabolism
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Piperazines*
  • Pyramidal Cells / chemistry
  • Pyramidal Cells / diagnostic imaging
  • Pyramidal Cells / metabolism
  • Pyridines*
  • Receptors, Serotonin / analysis
  • Receptors, Serotonin / chemistry
  • Receptors, Serotonin / metabolism*
  • Receptors, Serotonin, 5-HT1
  • Schizophrenia / diagnosis
  • Schizophrenia / diagnostic imaging*
  • Schizophrenia / metabolism
  • Serotonin Antagonists*
  • Temporal Lobe / chemistry
  • Temporal Lobe / metabolism
  • Tomography, Emission-Computed / methods
  • Tomography, Emission-Computed / statistics & numerical data*


  • Piperazines
  • Pyridines
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Serotonin Antagonists
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide