Dopamine and serotonin transporters in patients with schizophrenia: an imaging study with [(123)I]beta-CIT.
BACKGROUND
Several lines of evidence derived from imaging and postmortem studies suggest that schizophrenia is associated with hyperactivity of dopamine function and deficiency in serotonin (5-HT) function. The aim of this study was to investigate potential alterations of striatal dopamine transporters (DAT) and brainstem serotonin transporters (SERT) density in schizophrenia.


METHODS
Striatal DAT and brainstem SERT were measured in 24 patients with schizophrenia and 22 matched healthy control subjects using single photon emission computed tomography and [(123)I]beta-CIT. In this cohort of subjects, we previously reported an increase in striatal amphetamine-induced dopamine release, measured as the displacement of the D(2) receptor radiotracer [(123)I]IBZM.


RESULTS
No differences were observed between patients and control subjects in the equilibrium uptake ratio (V(3)") of [(123)I]beta-CIT in the striatum, indicating that schizophrenia is not generally associated with an alteration of striatal DAT density; however, a trend level association (p =.07) was observed in patients with schizophrenia between low striatal [(123)I]beta-CIT V(3)" and severity of negative symptoms. After controlling for age, striatal [(123)I]beta-CIT V(3)" in patients was not associated with duration of illness, suggesting that this relative deficit was not secondary to a neurodegenerative process. No correlation was observed between DAT density and amphetamine-induced dopamine release, either in the patients or in the controls. Brainstem [(123)I]beta-CIT V(3)" was unaffected in patients with schizophrenia, and was unrelated to symptomatology.


CONCLUSIONS
Schizophrenia is generally not associated with alterations of DAT in the striatum or SERT in the brainstem. In some patients, a relative deficit in dopamine nerve terminals might play a role in the pathophysiology of negative symptoms.
Laruelle
M
M
New York State Psychiatric Institute, Columbia University College of Physicians and Surgeons, New York 10032, USA.
Abi-Dargham
A
A
van Dyck
C
C
Gil
R
R
D'Souza
D C
DC
Krystal
J
J
Seibyl
J
J
Baldwin
R
R
Innis
R
R
D000328:Adult; D000367:Age Factors; D001933:Brain Stem / Q000000981:diagnostic imaging / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D016022:Case-Control Studies; D003042:Cocaine / Q000031:analogs & derivatives*; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D012559:Schizophrenia / Q000000981:diagnostic imaging* / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493214:SLC6A3 protein, human; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D003042:Cocaine; D004298:Dopamine