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

• Published in: Biological psychiatry (1969) Vol. 44; no. 11; pp. 1090 - 1098
• Main Authors: Malison, Robert T, Price, Lawrence H, Berman, Robert, van Dyck, Christopher H, Pelton, Gregory H, Carpenter, Linda, Sanacora, Gerard, Owens, Michael J, Nemeroff, Charles B, Rajeevan, Nallakandi, Baldwin, Robert M, Seibyl, John P, Innis, Robert B, Charney, Dennis S
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.12.1998; Elsevier Science
• Subjects: [ 123I]β-CIT; Adult; Adult and adolescent clinical studies; Antidepressive Agents - pharmacokinetics; Antidepressive Agents - therapeutic use; Biological and medical sciences; Brain - diagnostic imaging; Brain - physiopathology; Brain Stem - physiopathology; Carrier Proteins - physiology; Cocaine - analogs & derivatives; Cocaine - pharmacokinetics; Cocaine - therapeutic use; Depression; Depressive Disorder - diagnosis; Depressive Disorder - physiopathology; Female; Humans; Major depression; Male; Medical sciences; Membrane Glycoproteins - physiology; Membrane Transport Proteins; Middle Aged; Mood disorders; Nerve Tissue Proteins; paroxetine; Paroxetine - blood; Psychiatric Status Rating Scales; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; seratonin transporter platelets; Serotonin - physiology; Serotonin Plasma Membrane Transport Proteins; SPECT; Tomography, Emission-Computed, Single-Photon; paroxetine; [ 123I]β-CIT; Major depression; SPECT; seratonin transporter platelets; Mood disorder; Availability; Human; Paroxetine; Pathophysiology; Serotonin; Brain stem; Biological transport; Central nervous system; Depression; Binding site; Serotoninergic neuron; Platelet; Brain (vertebrata)
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/S0006-3223(98)00272-8

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 (V 3″ = (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 V 3″ 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 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.