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PET imaging of dopamine-D2 receptor internalization in schizophrenia.
Mol Psychiatry. 2018 06; 23(6):1506-1511.MP

Abstract

Recent genetic, molecular and post-mortem studies suggest impaired dopamine (DA)-D2 receptor (D2R) trafficking in patients with schizophrenia (SZ). Imaging and preclinical studies have shown agonist-induced D2R internalization can be imaged with positron emission tomography (PET) using D2R radiotracers combined with psychostimulant challenge. This is feasible if radiotracer binding is measured when postchallenge DA levels have returned to baseline, following the initial competition phase between DA and radiotracer for binding to D2R. Here we used 'late-phase' imaging after challenge to test the hypothesis that impaired D2R internalization in SZ leads to blunted late-phase displacement, or a faster return to baseline, in patients compared with healthy controls (HCs). We imaged 10 patients with SZ and 9 HCs with PET and [11C]raclopride at baseline and two times (3-5 and 6-10 h) following 0.5 mg kg-1 dextroamphetamine. We measured binding potential relative to non-displaceable compartment (BPND) and derived percent reduction from baseline (ΔBPND) for each postamphetamine scan. To test the hypothesis that time course of return of striatal BPND to baseline differed between SZ and HCs, we implemented a linear model with ΔBPND as dependent variable, time after amphetamine as repeated measure and time after amphetamine and diagnostic group as fixed effects. Neither diagnostic group nor interaction of diagnostic group-by-time after amphetamine significantly affected striatal ΔBPND (F=1.38, P=0.26; F=0.51, P=0.61). These results show similar pattern of return of BPND to baseline as a function of time in patients with SZ and HC, suggesting that striatal D2R internalization as measured by our imaging paradigm is normal in patients with SZ.

Authors+Show Affiliations

Department of Psychiatry, Stony Brook University School of Medicine, SUNY at Stony Brook, Health Sciences T10-041-L, Stony Brook, NY, USA.Department of Psychiatry, Stony Brook University School of Medicine, SUNY at Stony Brook, Health Sciences T10-041-L, Stony Brook, NY, USA.Department of Psychiatry, Stony Brook University School of Medicine, SUNY at Stony Brook, Health Sciences T10-041-L, Stony Brook, NY, USA.Department of Psychiatry, Stony Brook University School of Medicine, SUNY at Stony Brook, Health Sciences T10-041-L, Stony Brook, NY, USA.Department of Psychiatry, Stony Brook University School of Medicine, SUNY at Stony Brook, Health Sciences T10-041-L, Stony Brook, NY, USA.Department of Psychiatry, Stony Brook University School of Medicine, SUNY at Stony Brook, Health Sciences T10-041-L, Stony Brook, NY, USA.Department of Psychiatry, Stony Brook University School of Medicine, SUNY at Stony Brook, Health Sciences T10-041-L, Stony Brook, NY, USA.Department of Psychiatry, Stony Brook University School of Medicine, SUNY at Stony Brook, Health Sciences T10-041-L, Stony Brook, NY, USA.Department of Psychiatry, Stony Brook University School of Medicine, SUNY at Stony Brook, Health Sciences T10-041-L, Stony Brook, NY, USA.Department of Psychiatry, Stony Brook University School of Medicine, SUNY at Stony Brook, Health Sciences T10-041-L, Stony Brook, NY, USA.Department of Psychiatry, Stony Brook University School of Medicine, SUNY at Stony Brook, Health Sciences T10-041-L, Stony Brook, NY, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28507321

Citation

Weinstein, J J., et al. "PET Imaging of dopamine-D2 Receptor Internalization in Schizophrenia." Molecular Psychiatry, vol. 23, no. 6, 2018, pp. 1506-1511.
Weinstein JJ, van de Giessen E, Rosengard RJ, et al. PET imaging of dopamine-D2 receptor internalization in schizophrenia. Mol Psychiatry. 2018;23(6):1506-1511.
Weinstein, J. J., van de Giessen, E., Rosengard, R. J., Xu, X., Ojeil, N., Brucato, G., Gil, R. B., Kegeles, L. S., Laruelle, M., Slifstein, M., & Abi-Dargham, A. (2018). PET imaging of dopamine-D2 receptor internalization in schizophrenia. Molecular Psychiatry, 23(6), 1506-1511. https://doi.org/10.1038/mp.2017.107
Weinstein JJ, et al. PET Imaging of dopamine-D2 Receptor Internalization in Schizophrenia. Mol Psychiatry. 2018;23(6):1506-1511. PubMed PMID: 28507321.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PET imaging of dopamine-D2 receptor internalization in schizophrenia. AU - Weinstein,J J, AU - van de Giessen,E, AU - Rosengard,R J, AU - Xu,X, AU - Ojeil,N, AU - Brucato,G, AU - Gil,R B, AU - Kegeles,L S, AU - Laruelle,M, AU - Slifstein,M, AU - Abi-Dargham,A, Y1 - 2017/05/16/ PY - 2017/01/06/received PY - 2017/03/22/revised PY - 2017/04/04/accepted PY - 2017/5/17/pubmed PY - 2019/3/19/medline PY - 2017/5/17/entrez SP - 1506 EP - 1511 JF - Molecular psychiatry JO - Mol Psychiatry VL - 23 IS - 6 N2 - Recent genetic, molecular and post-mortem studies suggest impaired dopamine (DA)-D2 receptor (D2R) trafficking in patients with schizophrenia (SZ). Imaging and preclinical studies have shown agonist-induced D2R internalization can be imaged with positron emission tomography (PET) using D2R radiotracers combined with psychostimulant challenge. This is feasible if radiotracer binding is measured when postchallenge DA levels have returned to baseline, following the initial competition phase between DA and radiotracer for binding to D2R. Here we used 'late-phase' imaging after challenge to test the hypothesis that impaired D2R internalization in SZ leads to blunted late-phase displacement, or a faster return to baseline, in patients compared with healthy controls (HCs). We imaged 10 patients with SZ and 9 HCs with PET and [11C]raclopride at baseline and two times (3-5 and 6-10 h) following 0.5 mg kg-1 dextroamphetamine. We measured binding potential relative to non-displaceable compartment (BPND) and derived percent reduction from baseline (ΔBPND) for each postamphetamine scan. To test the hypothesis that time course of return of striatal BPND to baseline differed between SZ and HCs, we implemented a linear model with ΔBPND as dependent variable, time after amphetamine as repeated measure and time after amphetamine and diagnostic group as fixed effects. Neither diagnostic group nor interaction of diagnostic group-by-time after amphetamine significantly affected striatal ΔBPND (F=1.38, P=0.26; F=0.51, P=0.61). These results show similar pattern of return of BPND to baseline as a function of time in patients with SZ and HC, suggesting that striatal D2R internalization as measured by our imaging paradigm is normal in patients with SZ. SN - 1476-5578 UR - https://www.unboundmedicine.com/medline/citation/28507321/PET_imaging_of_dopamine_D2_receptor_internalization_in_schizophrenia_ L2 - https://doi.org/10.1038/mp.2017.107 DB - PRIME DP - Unbound Medicine ER -