Striatal and extrastriatal dopamine D2/D3 receptors in schizophrenia evaluated with [18F]fallypride positron emission tomography.
BACKGROUND
Alterations in dopamine D(2)/D(3) receptor binding have been reported in schizophrenia, and a meta-analysis of imaging studies has shown a modest elevation in striatum. Newer radioligands now allow the assessment of these receptors in extrastriatal regions. We used positron emission tomography with [(18)F]fallypride to evaluate D(2)/D(3) receptors in both striatal and extrastriatal regions in schizophrenia.


METHODS
Twenty-one patients with schizophrenia and 22 matched healthy control subjects were scanned with an ECAT EXACT HR+ camera. Two-tissue compartment modeling and the reference tissue method gave binding potentials relative to nondisplaceable uptake, total plasma concentration, and free plasma concentration. These were compared between groups in five striatal and eight extrastriatal regions. Several regional volumes were lower in the patient group, and positron emission tomography data were corrected for partial volume effects.


RESULTS
Binding potential values differed in three regions between groups. Values for binding potential relative to nondisplaceable uptake from two-tissue compartment modeling in patients and control subjects, respectively, were 28.7 ± 6.8 and 25.3 ± 4.3 in postcommissural caudate, 2.9 ± .7 and 2.6 ± .4 in thalamus, and 1.8 ± .5 and 2.1 ± .7 in uncus. Loss of D(2)/D(3) receptors with age was found in striatal and extrastriatal regions and was greater in neocortex.


CONCLUSIONS
Our study found selective alterations in D(2)/D(3) receptors in striatal and extrastriatal regions, consistent with some but not all previously published reports. As previously shown for the striatum, a more sensitive imaging approach for studying the role of dopamine in the pathophysiology of schizophrenia might be assessment of neurotransmitter levels rather than D(2)/D(3) receptor levels in extrastriatal regions.
Kegeles
Lawrence S
LS
Department of Psychiatry, Columbia University College of Physicians and Surgeons, and New York State Psychiatric Institute, New York 10032, USA. lsk5@columbia.edu
Slifstein
Mark
M
Xu
Xiaoyan
X
Urban
Nina
N
Thompson
Judy L
JL
Moadel
Tiffany
T
Harkavy-Friedman
Jill M
JM
Gil
Roberto
R
Laruelle
Marc
M
Abi-Dargham
Anissa
A
D000328:Adult; D000367:Age Factors; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001931:Brain Mapping; D016022:Case-Control Studies; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005462:Fluorine Radioisotopes / Q000378:metabolism; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods; D011485:Protein Binding / Q000187:drug effects; D011569:Psychiatric Status Rating Scales; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D012559:Schizophrenia / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology*; D055815:Young Adult
D014150:Antipsychotic Agents; D005462:Fluorine Radioisotopes; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3