TY - JOUR
T1 - D2/D3 dopamine receptor binding with [F-18]fallypride in thalamus and cortex of patients with schizophrenia
AU - Buchsbaum, Monte S.
AU - Christian, Bradley T.
AU - Lehrer, Douglas S.
AU - Narayanan, Tanjore K.
AU - Shi, Bingzhi
AU - Mantil, Joseph
AU - Kemether, Eileen
AU - Oakes, Terrence R.
AU - Mukherjee, Jogeshwar
N1 - Funding Information:
This work was supported by the Boonshoft Schizophrenia Center, the Wallace–Kettering Neuroscience Center, and by a grant to Dr. Buchsbaum, Anatomy and function of the thalamus in schizophrenia MH60023. The support of the United States Air Force, Air Force Research Laboratory (AFRL/HEOP), Air Force Materiel Command, under cooperative agreement F33615-98-2-6002, for use of imaging resources, is gratefully acknowledged. Marylin Brackney, Dr. King-Wai Chu, Kelly Dunigan, Kerry Kovacs, Candice Lee, Steve Mattmuller, Aaron Murray, Maruthi Narayanan, and Tonya Perkins, provided important technical support. Drs. Martin Satter (Kettering Medical Center), Nathaniel Alpert (Massachusetts General Hospital) and Chris Endres (Johns Hopkins) furnished valuable discussions on the analysis. MRI data were acquired by Dr. Mehdi Adenih. The project was approved by the IRBs of Kettering Medical Center, Wright State University and Mount Sinai School of Medicine. Gerald M. Szkotnicki, Executive Director, Wallace–Kettering Neuroscience Institute, Charles F. Kettering Memorial Hospital provided critical facilitating administrative and organizational support.
PY - 2006/7
Y1 - 2006/7
N2 - 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.
AB - 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.
KW - Dopamine receptor
KW - Laterality
KW - Limbic system
KW - Thalamic association nuclei
UR - http://www.scopus.com/inward/record.url?scp=33745375661&partnerID=8YFLogxK
U2 - 10.1016/j.schres.2006.03.042
DO - 10.1016/j.schres.2006.03.042
M3 - Article
C2 - 16713185
AN - SCOPUS:33745375661
SN - 0920-9964
VL - 85
SP - 232
EP - 244
JO - Schizophrenia Research
JF - Schizophrenia Research
IS - 1-3
ER -