D2/D3 dopamine receptor binding with [F-18]fallypride in thalamus and cortex of patients with schizophrenia.
BACKGROUND
Abnormalities in the dopaminergic system are implicated in schizophrenia. [F-18]fallypride is a highly selective, high affinity PET ligand well suited for measuring D2/D3 receptor availability in the extrastriatal regions of the brain including thalamus, prefrontal, cingulate, and temporal cortex, brain regions implicated in schizophrenia with other imaging modalities.


METHODS
Resting [F-18]fallypride PET studies were acquired together with anatomical MRI for accurate coregistration and image analysis on 15 drug naïve schizophrenics (10 men, 5 women, mean age 28.5 years) and 15 matched controls (9 men, 6 women, mean age 27.4 years). Dopamine D2/D3 receptor levels were measured as binding potential (BP). The fallypride BP images of each subject were spatially normalized and subsequently smoothed for group comparison. Measures of significance between the schizophrenic and control groups were determined using statistical parametric mapping (SPM). The medial dorsal nucleus and pulvinar were also traced on coregistered MRI for detailed assessment of BP in these regions.


RESULTS
The thalamus of patients with schizophrenia had lower [F-18]fallypride BP than normal controls and this was the brain area with the greatest difference (range -8.5% to -27.2%). Left medial dorsal nucleus and left pulvinar showed the greatest decreases (-21.6% and -27.2% respectively). The patients with schizophrenia also demonstrated D2/D3 BP reduction in the amygdala region, cingulate gyrus, and the temporal cortices.


CONCLUSIONS
These findings suggest that drug naïve patients with schizophrenia have significant reductions in extrastratial D2/D3 receptor availability. The reductions were most prominent in regions of the thalamus, replicating other studies both with high affinity D2/D3 ligands and consistent with FDG-PET studies, further supporting the hypothesis of thalamic abnormalities in this patient population.
Buchsbaum
Monte S
MS
Department of Psychiatry, Mt. Sinai School of Medicine, New York, NY 10029, USA. Monte.buchsbaum@mssm.edu
Christian
Bradley T
BT
Lehrer
Douglas S
DS
Narayanan
Tanjore K
TK
Shi
Bingzhi
B
Mantil
Joseph
J
Kemether
Eileen
E
Oakes
Terrence R
TR
Mukherjee
Jogeshwar
J
D000328:Adult; D001549:Benzamides / Q000493:pharmacokinetics; D001665:Binding Sites / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D008954:Models, Biological; D049268:Positron-Emission Tomography; D011759:Pyrrolidines / Q000493:pharmacokinetics; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000187:drug effects* / Q000378:metabolism*; D012559:Schizophrenia / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology; D013788:Thalamus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology
D001549:Benzamides; D005462:Fluorine Radioisotopes; C094948:N-((1-allyl-2-pyrrolidinyl)methyl)-5-(3-fluoropropyl)-2,3-dimethoxybenzamide; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3