Increase in thalamic binding of [(11)C]PE2I in patients with schizophrenia: a positron emission tomography study of dopamine transporter.

Previous in vivo imaging studies reported no difference in dopamine transporter (DAT) bindings in the striatum between control subjects and patients with schizophrenia. However, as the signals of radioligands with moderate affinity were insufficient for allowing the evaluation of small amounts of DAT, DAT binding in extrastriatal regions has not been determined. Positron emission tomography scanning using [(11)C]PE2I was performed on eight patients with schizophrenia and twelve normal control subjects. Binding potential (BP(ND)) for DAT in the caudate, putamen, thalamus and substantia nigra was calculated, using the cerebellum as reference region. In patients with schizophrenia, clinical symptoms were evaluated by Positive and Negative Syndrome Scale (PANSS). BP(ND) in the thalamus of patients with schizophrenia was significantly higher than in control subjects (P=0.044). In patients with schizophrenia, there were significantly positive correlations between BP(ND) in the thalamus and total (r=0.75), positive (r=0.78) and negative PANSS scores (r=0.82). Altered DAT in the thalamus might be related to the pathophysiology and clinical symptoms of schizophrenia.

[1]  Christer Halldin,et al.  Measurement of Striatal and Extrastriatal Dopamine Transporter Binding with High-Resolution PET and [11C]PE2I: Quantitative Modeling and Test—Retest Reproducibility , 2008, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[2]  P. Chen,et al.  Associated alterations of striatal dopamine D2/D3 receptor and transporter binding in drug-naive patients with schizophrenia: a dual-isotope SPECT study. , 2004, The American journal of psychiatry.

[3]  D. Melchitzky,et al.  Dopamine transporter-immunoreactive axons in the mediodorsal thalamic nucleus of the macaque monkey , 2001, Neuroscience.

[4]  Bradley T. Christian,et al.  D2/D3 dopamine receptor binding with [F-18]fallypride in thalamus and cortex of patients with schizophrenia , 2006, Schizophrenia Research.

[5]  S. Houle,et al.  Novel Radiotracers for Imaging the Serotonin Transporter by Positron Emission Tomography: Synthesis, Radiosynthesis, and in Vitro and ex Vivo Evaluation of (11)C-Labeled 2-(Phenylthio)araalkylamines. , 2000, Journal of medicinal chemistry.

[6]  H. Möller,et al.  The striatal dopamine transporter in first-episode, drug-naive schizophrenic patients: evaluation by the new SPECT-ligand[99mTc]TRODAT-1 , 2005, Journal of psychopharmacology.

[7]  Kun-Ju Lin,et al.  Dopamine transporter change in drug-naı̈ve schizophrenia: an imaging study with 99mTc-TRODAT-1 , 2003, Schizophrenia Research.

[8]  J. Meador-Woodruff,et al.  Thalamic dysfunction in schizophrenia: neurochemical, neuropathological, and in vivo imaging abnormalities , 2004, Schizophrenia Research.

[9]  Christer Halldin,et al.  Quantitative analyses of regional [11C]PE2I binding to the dopamine transporter in the human brain: a PET study , 2006, European Journal of Nuclear Medicine and Molecular Imaging.

[10]  A. Green Schizophrenia and comorbid substance use disorder: effects of antipsychotics. , 2005, The Journal of clinical psychiatry.

[11]  H. Möller,et al.  Dual-isotope SPECT imaging of striatal dopamine: First episode, drug naïve schizophrenic patients , 2008, Schizophrenia Research.

[12]  D. Guilloteau,et al.  Visualization of the Dopamine Transporter in the Human Brain Postmortem with the New Selective Ligand [125I]PE2I , 1999, NeuroImage.

[13]  D. Linszen,et al.  Dopamine transporter density in young patients with schizophrenia assessed with [123]FP-CIT SPECT , 2001, Schizophrenia Research.

[14]  G D Pearlson,et al.  PET study of competition between intravenous cocaine and [11C]raclopride at dopamine receptors in human subjects. , 1997, The American journal of psychiatry.

[15]  Nikolaos Koutsouleris,et al.  Striatal dopamine transporter availability is associated with the productive psychotic state in first episode, drug–naive schizophrenic patients , 2006, European Archives of Psychiatry and Clinical Neuroscience.

[16]  E. Fernandez-Egea,et al.  Lower striatal dopamine transporter binding in neuroleptic-naive schizophrenic patients is not related to antipsychotic treatment but it suggests an illness trait , 2007, Psychopharmacology.

[17]  K. Davis,et al.  Dopaminergic abnormalities in select thalamic nuclei in schizophrenia: involvement of the intracellular signal integrating proteins calcyon and spinophilin. , 2005, The American journal of psychiatry.

[18]  J. Krystal,et al.  Dopamine and serotonin transporters in patients with schizophrenia: an imaging study with [123I]β-CIT , 2000, Biological Psychiatry.

[19]  Christer Halldin,et al.  Dopamine D2 receptor binding in drug-naïve patients with schizophrenia examined with raclopride-C11 and positron emission tomography , 2006, Psychiatry Research: Neuroimaging.

[20]  J. Hietala,et al.  Striatal dopamine transporter binding in neuroleptic-naive patients with schizophrenia studied with positron emission tomography. , 2000, The American journal of psychiatry.

[21]  Sylvain Houle,et al.  Effects of Tryptophan Depletion on the Serotonin Transporter in Healthy Humans , 2005, Biological Psychiatry.

[22]  Hidehiko Takahashi,et al.  The Role of Extrastriatal Dopamine D2 Receptors in Schizophrenia , 2006, Biological Psychiatry.

[23]  Mark Slifstein,et al.  Effects of reduced endogenous 5‐HT on the in vivo binding of the serotonin transporter radioligand 11C‐DASB in healthy humans , 2005, Synapse.

[24]  F. Yasuno,et al.  Low dopamine d(2) receptor binding in subregions of the thalamus in schizophrenia. , 2004, The American journal of psychiatry.

[25]  Miguel Ángel García-Cabezas,et al.  Distribution of the dopamine innervation in the macaque and human thalamus , 2007, NeuroImage.

[26]  Harumasa Takano,et al.  Normal database of dopaminergic neurotransmission system in human brain measured by positron emission tomography , 2008, NeuroImage.

[27]  A. Oke,et al.  Elevated thalamic dopamine: possible link to sensory dysfunctions in schizophrenia. , 1987, Schizophrenia bulletin.

[28]  Yuan-Hwa Chou,et al.  [11C]PE2I: a highly selective radioligand for PET examination of the dopamine transporter in monkey and human brain , 2003, European Journal of Nuclear Medicine and Molecular Imaging.

[29]  C. Halldin,et al.  Decreased thalamic D2/D3 receptor binding in drug-naive patients with schizophrenia: a PET study with [11C]FLB 457. , 2003, The international journal of neuropsychopharmacology.