Striatal and Extrastriatal Dopamine D2/D3 Receptors in Schizophrenia Evaluated With [18F]fallypride Positron Emission Tomography

doi:10.1016/j.biopsych.2010.05.027

Biological Psychiatry

Volume 68, Issue 7, 1 October 2010, Pages 634-641

https://doi.org/10.1016/j.biopsych.2010.05.027 Get rights and content

Background

Alterations in dopamine D₂/D₃ 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 [¹⁸F]fallypride to evaluate D₂/D₃ 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 D₂/D₃ receptors with age was found in striatal and extrastriatal regions and was greater in neocortex.

Conclusions

Our study found selective alterations in D₂/D₃ 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 D₂/D₃ receptor levels in extrastriatal regions.

Section snippets

Subjects

Twenty-one patients and 22 matched healthy control subjects underwent a total of 43 [¹⁸F]fallypride scans (see Table 1 for clinical and demographic characteristics that include matching for age, gender, ethnicity, smoking status, and parental but not subject socioeconomic status [17]). Patients were medically healthy and met inclusion criteria for schizophrenia or schizoaffective disorder but no other DSM-IV (18) Axis I diagnosis; there was no substance abuse by history confirmed with negative

Results

Emission data were stable and continuous across the blocks of acquisition time in both patient and healthy control groups (Figure S1 in Supplement 1). Injected doses, masses, and specific activities of [¹⁸F]fallypride did not differ between the patient and healthy control groups (Table S1 in Supplement 1).

Discussion

We found baseline abnormalities in D₂/D₃ receptor binding in particular striatal and extrastriatal regions in this study. Increases in BP in thalamus and postcommissural caudate and a decrease in uncus were each detected with more than one outcome measure. Our finding in postcommissural caudate is consistent with prior literature showing a moderate increase in striatal D₂/D₃ receptor binding in schizophrenia (1, 36). The increase we found in thalamus does not replicate recent reports, and D₂/D₃

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Archival ReportStriatal and Extrastriatal Dopamine D2/D3 Receptors in Schizophrenia Evaluated With [18F]fallypride Positron Emission Tomography

Background

Methods

Results

Conclusions

Section snippets

Subjects

Results

Discussion

Nucl Med Biol

Biol Psychiatry

Neuroimage

Schizophr Res

Schizophr Res

Biol Psychiatry

Biol Psychiatry

Neurobiol Aging

Life Sci

Neurochemical and neuropharmacological imaging in schizophrenia

Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug free schizophrenic subjects

Proc Natl Acad Sci U S A

Identification of extrastriatal dopamine D2 receptors in postmortem human brain with [125I]epidipride

Brain Res

Dopamine D2 receptors in the cerebral cortex: Distribution and pharmacological characterization with [3H]raclopride

Proc Natl Acad Sci U S A

Localization of dopamine D3 receptors to mesolimbic and D2 receptors to mesofrontal regions of human forebrain

Proc Natl Acad Sci U S A

Distribution of D1- and D2-dopamine receptors, and dopamine and its metabolites in the human brain

Neuropsychopharmacology

Characterization and distribution of [125I]epidepride binding to dopamine D2 receptors in basal ganglia and cortex in human brain

J Pharmacol Exp Ther

Carbon-11-FLB 457: A radioligand for extrastriatal D2 dopamine receptors

J Nucl Med

In vivo affinity of [18F]fallypride for striatal and extrastriatal dopamine D2 receptors in nonhuman plrimates

Psychopharmacology (Berl)

Increased concentrations and lateral asymmetry of amygdala dopamine in schizophrenia

Nature

Lamina-specific alterations in the dopamine innervation of the prefrontal cortex in schizophrenic subjects

Am J Psychiatry

Evaluation of d-amphetamine effects on the binding of dopamine D-2 receptor radioligand, F-18-fallypride in nonhuman primates using positron emission tomography

Synapse

PET measurements of endogenous neurotransmitter activity using high and low affinity radiotracers

Neuroimage

Imaging human mesolimbic dopamine transmission with positron emission tomographyPart II: Amphetamine-induced dopamine release in the functional subdivisions of the striatum

J Cereb Blood Flow Metab

Four Factor Index of Social Status

Diagnostic and Statistical Manual of Mental Disorders

Dose-occupancy study of striatal and extrastriatal dopamine D2 receptors by aripiprazole in schizophrenia with PET and [18F]fallypride

Neuropsychopharmacology

Performance evaluation of a whole-body PET scanner using the NEMA protocolNational Electrical Manufacturers Association

J Nucl Med

Archival Report
Striatal and Extrastriatal Dopamine D₂/D₃ Receptors in Schizophrenia Evaluated With [¹⁸F]fallypride Positron Emission Tomography

Identification of extrastriatal dopamine D2 receptors in postmortem human brain with [¹²⁵I]epidipride

Dopamine D₂ receptors in the cerebral cortex: Distribution and pharmacological characterization with [³H]raclopride