Reduced brain serotonin transporter availability in major depression as measured by [123I]-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane and single photon emission computed tomography.
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] beta-CIT SPECT and platelet [3H]paroxetine binding.


METHODS
Drug-free depressed and healthy subjects were injected with 211 +/- 22 MBq [123I] beta-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] beta-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.
Malison
R T
RT
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Price
L H
LH
Berman
R
R
van Dyck
C H
CH
Pelton
G H
GH
Carpenter
L
L
Sanacora
G
G
Owens
M J
MJ
Nemeroff
C B
CB
Rajeevan
N
N
Baldwin
R M
RM
Seibyl
J P
JP
Innis
R B
RB
Charney
D S
DS
D000328:Adult; D000928:Antidepressive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001921:Brain / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D001933:Brain Stem / Q000503:physiopathology; D002352:Carrier Proteins / Q000502:physiology*; D003042:Cocaine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D003866:Depressive Disorder / Q000175:diagnosis* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D017374:Paroxetine / Q000097:blood; D011569:Psychiatric Status Rating Scales; D012701:Serotonin / Q000502:physiology*; D050486:Serotonin Plasma Membrane Transport Proteins; D015899:Tomography, Emission-Computed, Single-Photon
D000928:Antidepressive Agents; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D017374:Paroxetine; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D003042:Cocaine