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

TLDR

Prior research indicates reduced serotonin transporter density in platelets and post‑mortem brain tissue of depressed patients. The study aimed to assess whether unipolar major depression is associated with reduced SERT availability using brainstem SPECT and platelet binding assays. Drug‑free subjects were injected with 211 MBq [123I]β‑CIT, imaged 24 h later, and SERT availability was quantified by the specific‑to‑nonspecific uptake ratio V3″, proportional to binding potential. Results showed a significant reduction in brainstem V3″ values in depressed versus healthy subjects (3.1 ± 0.9 vs.

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 [123I]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 (Bmax/Kd), 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 (Bmax = 2389 ± 484 vs. 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.