Reduced brain serotonin transporter availability in major depression as measured by [123I]-2β-carbomethoxy-3β-(4-iodophenyl)tropane and single photon emission computed tomography

Robert T. Malison, Lawrence H. Price, Robert Berman, Christopher H. Van Dyck, Gregory H. Pelton, Linda Carpenter, Gerard Sanacora, Michael J. Owens, Charles B. Nemeroff, Nallakandi Rajeevan, Robert M. Baldwin, John P. Seibyl, Robert B. Innis, Dennis S. Charney

Research output: Contribution to journalArticle

402 Scopus citations

Abstract

Background: Prior research has suggested reductions in the density of serotonin transporter (SERT) binding sites in blood platelets and post- mortem brain tissue of depressed patients. We sought to determine whether patients with unipolar major depression have diminished SERT availability as assessed by both brainstem [1231]β-CIT SPECT and platelet [3H]paroxetine binding. Methods: Drug-free depressed and healthy subjects were injected with 211 ± 22 MBq [123I]β- CIT and imaged 24 ± 2 h later under equilibrium conditions. A ratio of specific to nonspecific brain uptake (V3/'' = (brainstem-occipital)/occipital), a measure proportional to the binding potential (B(max)/K(d)), was used for all comparisons. Results: Results showed a statistically significant reduction in brainstem V3/'' values in depressed as compared to healthy subjects (3.1 ± .9 vs. 3.8 ± .8, p = .02). Platelet [3H]paroxetine binding was not altered (B(max) = 2389 ± 484 v. 2415 ± 538 fmol/mg protein, p = .91) and was not significantly correlated with brainstem [123I]β-CIT binding (r = -0.14, p = .48). Conclusions: These data are the first to suggest reductions in the density of brain SERT binding sites in living depressed patients. These findings provide further support for a preeminent role for alterations in serotonergic neurons in the pathophysiology of depression.

Original languageEnglish (US)
Pages (from-to)1090-1098
Number of pages9
JournalBiological Psychiatry
Volume44
Issue number11
DOIs
StatePublished - Dec 1 1998
Externally publishedYes

Keywords

  • [I]̄-CIT
  • Major depression
  • Paroxetine
  • Seratonin transporter platelets
  • SPECT

ASJC Scopus subject areas

  • Biological Psychiatry

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    Malison, R. T., Price, L. H., Berman, R., Van Dyck, C. H., Pelton, G. H., Carpenter, L., Sanacora, G., Owens, M. J., Nemeroff, C. B., Rajeevan, N., Baldwin, R. M., Seibyl, J. P., Innis, R. B., & Charney, D. S. (1998). Reduced brain serotonin transporter availability in major depression as measured by [123I]-2β-carbomethoxy-3β-(4-iodophenyl)tropane and single photon emission computed tomography. Biological Psychiatry, 44(11), 1090-1098. https://doi.org/10.1016/S0006-3223(98)00272-8