Brain serotonin2 receptors in major depression: a positron emission tomography study

Arch Gen Psychiatry. 2000 Sep;57(9):850-8. doi: 10.1001/archpsyc.57.9.850.


Background: Postmortem and brain imaging studies that measured brain serotinin(2) (5-HT(2)) receptors in major depression reported an increase, decrease, and no change compared with controls. In this study, we assessed brain 5-HT(2) receptors in 20 depressed patients (mean +/- SD age, 40.1 +/- 9.5 years; range, 22-60 years) and 20 healthy controls similar in age (37.2 +/- 12.6 years; range, 19-59 years) using positron emission tomography and setoperone labeled with fluorine 18 ([(18)F]setoperone).

Methods: Patients with DSM-IV major depression and healthy controls underwent scanning with [(18)F]setoperone. All study subjects were drug free for at least 2 weeks. The 5-HT(2) binding images were created using region-to-cerebellum ratios. The differences in 5-HT(2) receptor binding potential between the two groups were determined with statistical parametric mapping software and region of interest analysis.

Results: There was a significant negative correlation between 5-HT(2) receptor binding potential and age in both patients and controls, and the magnitude of this correlation was similar in both groups. Both statistical parametric mapping and region of interest analyses showed that, compared with healthy controls, depressed patients had significantly lower 5-HT(2) receptor binding potential in frontal, temporal, parietal, and occipital cortical regions. Statistical parametric mapping analysis showed that the mean decrease in 5-HT(2) receptor binding potential for the entire cluster in these regions was 22%, and it ranged from 22% to 27% for local maxima within the clusters of significant voxels.

Conclusion: This study suggests that brain 5-HT(2) receptors are decreased in patients with major depression.

MeSH terms

  • Adult
  • Age Factors
  • Brain / diagnostic imaging*
  • Brain / metabolism*
  • Cerebellum / chemistry
  • Cerebellum / diagnostic imaging
  • Cerebellum / metabolism
  • Depressive Disorder / diagnostic imaging*
  • Depressive Disorder / metabolism*
  • Female
  • Fluorine Radioisotopes
  • Frontal Lobe / chemistry
  • Frontal Lobe / diagnostic imaging
  • Frontal Lobe / metabolism
  • Humans
  • Male
  • Middle Aged
  • Occipital Lobe / chemistry
  • Occipital Lobe / diagnostic imaging
  • Occipital Lobe / metabolism
  • Parietal Lobe / chemistry
  • Parietal Lobe / diagnostic imaging
  • Parietal Lobe / metabolism
  • Pyrimidinones
  • Receptors, Serotonin / analysis
  • Receptors, Serotonin / metabolism*
  • Sex Factors
  • Temporal Lobe / chemistry
  • Temporal Lobe / diagnostic imaging
  • Temporal Lobe / metabolism
  • Tomography, Emission-Computed / statistics & numerical data*


  • Fluorine Radioisotopes
  • Pyrimidinones
  • Receptors, Serotonin
  • setoperone