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Simultaneous Measurement of Dopamine Transporters and D2/D3 Receptors in Drug Naïve Schizophrenic Patients

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Objective: Previous single photon emission computed tomography (SPECT) studies have demonstrated that co-injection of radiotracers 99mTc-TRODAT and 123IBZM can assess both presynaptic, dopamine transporters (DATs), and postsynaptic, dopamine D2/D3 receptors, markers of dopaminergic system simultaneously. The aim of this study was to determine both DATs and dopamine D2/D3 receptors in drug naïve schizophrenic patients. Methods: Severn drug naïve schizophrenic patients and eleven age-matched healthy controls were recruited. Each subject received one SPECT measurement after intravenous co-administration of 99mTc-TRODAT and 123IBZM and one brain MRI scan. A ratio equilibrium model was applied to calculate the specific uptake ratio (SUR) which corresponds to the ratio of Bmax (receptor density) and KD (affinity). Results: The results showed that the SUR of DATs binding was not significantly different between healthy controls and drug naïve schizophrenic patients (2.92±0.62 vs. 2.65±0.27, p=0.052) and, however, the SUR of dopamine D2/D3 receptors binding was significantly lower in drug naïve schizophrenic patients than those in healthy controls (2.79±0.54 vs. 3.90±0.58, p=0.001). Additionally, there was a significant correlation between left and right binding for both DATs (r=0.80, p=0.003) and dopamine D2/D3 receptors (r=0.96, p=0.000) in healthy controls but not seen in drug naïve schizophrenic patients (r=0.54, p=0.20 for DATs, r=0.70, p=0.08 for dopamine D2/D3 receptors). Conclusion: This study provides evidences to support the idea that abnormalities of dopaminergic system in schizophrenia and further elucidates the disruption of inter-hemispheric interaction of postsynaptic and presynaptic markers.

Abstract

Objective: Previous single photon emission computed tomography (SPECT) studies have demonstrated that co-injection of radiotracers 99mTc-TRODAT and 123IBZM can assess both presynaptic, dopamine transporters (DATs), and postsynaptic, dopamine D2/D3 receptors, markers of dopaminergic system simultaneously. The aim of this study was to determine both DATs and dopamine D2/D3 receptors in drug naïve schizophrenic patients. Methods: Severn drug naïve schizophrenic patients and eleven age-matched healthy controls were recruited. Each subject received one SPECT measurement after intravenous co-administration of 99mTc-TRODAT and 123IBZM and one brain MRI scan. A ratio equilibrium model was applied to calculate the specific uptake ratio (SUR) which corresponds to the ratio of Bmax (receptor density) and KD (affinity). Results: The results showed that the SUR of DATs binding was not significantly different between healthy controls and drug naïve schizophrenic patients (2.92±0.62 vs. 2.65±0.27, p=0.052) and, however, the SUR of dopamine D2/D3 receptors binding was significantly lower in drug naïve schizophrenic patients than those in healthy controls (2.79±0.54 vs. 3.90±0.58, p=0.001). Additionally, there was a significant correlation between left and right binding for both DATs (r=0.80, p=0.003) and dopamine D2/D3 receptors (r=0.96, p=0.000) in healthy controls but not seen in drug naïve schizophrenic patients (r=0.54, p=0.20 for DATs, r=0.70, p=0.08 for dopamine D2/D3 receptors). Conclusion: This study provides evidences to support the idea that abnormalities of dopaminergic system in schizophrenia and further elucidates the disruption of inter-hemispheric interaction of postsynaptic and presynaptic markers.

참고문헌 (40)

  1. Soares JC, "Neurochemical brain imaging investigations of schizophrenia", Biol Psychiatry, 46, pp.600~615 (1999)
  2. Seeman P, "Schizophrenia as a brain disease. The dopamine receptor story", Arch Neurol, 50, pp.1093~1095 (1993)
  3. Sedvall G, "Imaging of neurotransmitter receptors in the living human brain", Arch Gen Psychiatry, 43, pp.995~1005 (1986)
  4. Farde L, "Quantitative analysis of D2 dopamine receptor binding in the living human brain by PET", Science, 231, pp.258~261 (1986)
  5. Wagner HN Jr, "Imaging dopamine receptors in the human brain by positron tomography", Science, 221, pp.1264~1266 (1983)
  6. Laruelle M, "Imaging dopamine transmission in schizophrenia. A review and meta-analysis", Q J Nucl Med, 42, pp.211~221 (1998)
  7. Suhara T, "Decreased dopamine D2 receptor binding in the anterior cingulate cortex in schizophrenia", Arch Gen Psychiatry, 59, pp.25~30 (2002)
  8. FLB 457, "Int J Neuropsychopharmacol", 2003, 361~370
  9. Sotnikova TD, "Molecular biology, pharmacology and functional role of the plasma membrane dopamine transporter", CNS Neurol Disord Drug Targets, 5, pp.45~56 (2006)
  10. Laakso A, "Striatal dopamine transporter binding in neuroleptic-naive patients with schizophrenia studied with positron emission tomography", Am J Psychiatry, 157, pp.269~271 (2000)
  11. Hsiao MC, "Dopamine transporter change in drug-naive schizophrenia: an imaging study with 99mTc-TRODAT-1", Schizophr Res, 65, pp.39~46 (2003)
  12. Laakso A, "Decreased striatal dopamine transporter binding in vivo in chronic schizophrenia", Schizophr Res, 52, pp.115~120 (2001)
  13. Mozley LH, "Striatal dopamine transporters and cognitive functioning in healthy men and women", Am J Psychiatry, 158, pp.1492~1499 (2001)
  14. Chou YH, "Dopamine transporters and cognitive function in methamphetamine abuser after a short abstinence: A SPECT study", Eur Neuropsychopharmacol, 17, pp.46~52 (2007)
  15. Barnas C, "In vivo (123)I IBZM SPECT imaging of striatal dopamine 2 receptor occupancy in schizophrenic patients", Psychopharmacology (Berl), 157, pp.236~242 (2001)
  16. Yang YK, "Associated alterations of striatal dopamine D2", D3 receptor and transporter binding in drug-naive patients with schizophrenia: a dual-isotope SPECT study, 2004, pp.161, 1496~1498
  17. IBZM in normal and 6-OHDA-lesioned formosan rock monkeys, "Nucl Med Biol", 2002, 561~567
  18. Dresel SH, "Simultaneous SPECT studies of pre- and postsynaptic dopamine binding sites in baboons", J Nucl Med, 40, pp.660~666 (1999)
  19. Sheehan DV, "The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10", J Clin Psychiatry, 9(20), pp.22~33 (1998)
  20. American Psychiatric Association, "Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition - Text Revision (DSMIV-TR)", American Psychiatric Association, ~ (2000)
  21. Kung HF, "Development of Tc-99m labeled tropanes: TRODAT-1, as a dopamine transporter imaging agent", Nucl Med Biol, 28, pp.505~508 (2001)
  22. Tzen KY, "Differential diagnosis of Parkinson's disease and vascular parkinsonism by (99m)Tc-TRODAT-1", J Nucl Med, 42, pp.408~413 (2001)
  23. Kung MP, "The characterization of IBF as a new selective dopamine D-2 receptor imaging agent", J Nucl Med, 31, pp.648~654 (1990)
  24. Devous MD Sr, "Dual-isotope brain SPECT imaging with technetium-99m and iodine-123: validation by phantom studies", J Nucl Med, 33, pp.2030~2035 (1992)
  25. TRODAT-1 binding to dopamine transporters in nonhuman primates using single-photon emission tomography, "Eur J Nucl Med", 1999, 518~526
  26. TRODAT-1: a dopamine transporter imaging agent, "J Nucl Med", 1999, 150~158
  27. raclopride binding, "J Cereb Blood Flow Metab", 1998, 941~950
  28. raclopride: implications for positron emission tomography of the human brain, "Synapse", 1989, 96~97
  29. Laruelle M, "Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects", Proc Natl Acad Sci USA, 93, pp.9235~9240 (1996)
  30. Laruelle M, "Increased dopamine transmission in schizophrenia: relationship to illness phases", Biol Psychiatry, 46, pp.56~72 (1999)
  31. Seeman P, "Jellinger K, Gabriel E, et al. Bimodal distribution of dopamine receptor densities in brains of schizophrenics", Science, 225, pp.728~731 (1984)
  32. Chou YH, "Effect of amphetamine on extrastriatal D2 dopamine receptor binding in the primate brain: a PET study", Synapse, 38, pp.138~143 (2000)
  33. Laruelle M, "Imaging synaptic neurotransmission with in vivo binding competition techniques: a critical review", J Cereb Blood Flow Metab, 20, pp.423~451 (2000)
  34. Hietala J, "Presynaptic dopamine function in striatum of neuroleptic-naive schizophrenic patients", Lancet, 346, pp.1130~1131 (1995)
  35. Crow TJ, "Schizophrenia as failure of hemispheric dominance for language", Trends Neurosci, 20, pp.339~343 (1997)
  36. DeLisi LE, "Anomalous cerebral asymmetry and language processing in schizophrenia", Schizophr Bull, 23, pp.255~271 (1997)
  37. Falkai P, "Loss of sylvian fissure asymmetry in schizophrenia. A quantitative post mortem study", Schizophr Res, 7, pp.23~32 (1992)
  38. McGlashan TH, "Schizophrenia as a disorder of developmentally reduced synaptic connectivity", Arch Gen Psychiatry, 57, pp.637~648 (2000)
  39. Roberts RC, "The ultrastructural organization of the patch matrix compartments in the human striatum", J Comp Neurol, 452, pp.128~138 (2002)
  40. Roberts RC, "Synaptic differences in the patch matrix compartments of subjects with schizophrenia: a postmortem ultrastructural study of the striatum", Neurobiol Dis, 20, pp.324~335 (2005)

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