Low dopamine d(2) receptor binding in subregions of the thalamus in schizophrenia.

OBJECTIVE Several structural and functional brain imaging studies have pointed to a disturbance of thalamic subnuclei in patients with schizophrenia. The dopamine hypothesis of schizophrenia has, however, not been thoroughly examined in terms of this complex structure, which has connections with most brain regions of central interest in schizophrenia research. The aim of the present study was to examine dopamine D(2) receptor binding in subregions of the thalamus in patients with schizophrenia. METHOD The authors used positron emission tomography and the radioligand [(11)C]FLB457 to examine dopamine D(2) receptor binding in thalamic subregions of 10 drug-naive patients with schizophrenia. Binding potential was calculated by the reference tissue method and used as an index for dopamine D(2) receptor binding. Comparisons were made with 19 healthy subjects. Subregions of interest were defined on individual magnetic resonance images using a percentage-based operational approach. Clinical symptoms were rated by using the Brief Psychiatric Rating Scale (BPRS). RESULTS The [(11)C]FLB457 binding potential was lower in the central medial and posterior subregions of the thalamus in patients with schizophrenia. At a functional level, there was a significant negative correlation between binding potential and BPRS positive symptom scores. CONCLUSIONS The subregions with low D(2) receptor binding comprise primarily the dorsomedial nucleus and pulvinar, two important components in circuitries previously suggested in the pathophysiology of schizophrenia. Aberrant dopaminergic neurotransmission in thalamic subregions might be a mechanism underlying positive symptoms in schizophrenia.

[1]  Richard S. J. Frackowiak,et al.  Cortical and subcortical gray matter abnormalities in schizophrenia determined through structural magnetic resonance imaging with optimized volumetric voxel-based morphometry. , 2002, The American journal of psychiatry.

[2]  A. Minassian,et al.  Information processing deficits in acutely psychotic schizophrenia patients medicated and unmedicated at the time of admission. , 2002, The American journal of psychiatry.

[3]  Makoto Inoue,et al.  Template-Based Method for Multiple Volumes of Interest of Human Brain PET Images , 2002, NeuroImage.

[4]  S. Obayashi,et al.  Effect of endogenous dopamine on extrastriatal [11C]FLB 457 binding measured by PET , 2001, Synapse.

[5]  J. Sweeney,et al.  Thalamic volumes in patients with first-episode schizophrenia. , 2001, The American journal of psychiatry.

[6]  L. Siever,et al.  Magnetic resonance imaging of the thalamic mediodorsal nucleus and pulvinar in schizophrenia and schizotypal personality disorder. , 2001, Archives of general psychiatry.

[7]  Y. Sudo,et al.  Ten year progressive ventricular enlargement in schizophrenia: An MRI morphometrical study , 2001, Psychiatry and clinical neurosciences.

[8]  E G Jones,et al.  Subnucleus-specific loss of neurons in medial thalamus of schizophrenics. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[9]  D. German,et al.  Reduced number of mediodorsal and anterior thalamic neurons in schizophrenia , 2000, Biological Psychiatry.

[10]  A. Carlsson,et al.  Network interactions in schizophrenia — therapeutic implications , 2000, Brain Research Reviews.

[11]  Christer Halldin,et al.  PET Mapping of Extrastriatal D2-like Dopamine Receptors in the Human Brain Using an Anatomic Standardization Technique and [11C]FLB 457 , 1999, NeuroImage.

[12]  C. Halldin,et al.  Quantification of [11C]FLB 457 Binding to Extrastriatal Dopamine Receptors in the Human Brain , 1999, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[13]  A. Clair,et al.  Choosing negative symptom instruments: issues of representation and redundancy , 1999, Psychiatry Research.

[14]  C Crouzel,et al.  Carbon-11 epidepride: a suitable radioligand for PET investigation of striatal and extrastriatal dopamine D2 receptors. , 1999, Nuclear medicine and biology.

[15]  Christer Halldin,et al.  Extrastriatal dopamine D2 receptor density and affinity in the human brain measured by 3D PET. , 1999, The international journal of neuropsychopharmacology.

[16]  R. Gur,et al.  Subcortical MRI volumes in neuroleptic-naive and treated patients with schizophrenia. , 1998, The American journal of psychiatry.

[17]  C. Heimberg,et al.  Regional proton magnetic resonance spectroscopy in schizophrenia and exploration of drug effect , 1998, Psychiatry Research: Neuroimaging.

[18]  Ron Kikinis,et al.  Volumetric Evaluation of the Thalamus in Schizophrenic Male Patients Using Magnetic Resonance Imaging , 1998, Biological Psychiatry.

[19]  M S Buchsbaum,et al.  Prefrontal cortex glucose metabolism and startle eyeblink modification abnormalities in unmedicated schizophrenia patients. , 1998, Psychophysiology.

[20]  N. Swerdlow,et al.  Regulation of Prepulse Inhibition by Ventral Pallidal Projections , 1997, Brain Research Bulletin.

[21]  V. M. Rodríguez,et al.  Fronto-striato-thalamic perfusion and clozapine response in treatment-refractory schizophrenic patients. A99mTc-HMPAO study , 1997, Psychiatry Research: Neuroimaging.

[22]  Christer Halldin,et al.  A PET-study of [11C]FLB 457 binding to extrastriatal D2-dopamine receptors in healthy subjects and antipsychotic drug-treated patients , 1997, Psychopharmacology.

[23]  J. Joyce,et al.  Disrupted pattern of D2 dopamine receptors in the temporal lobe in schizophrenia. A postmortem study. , 1997, Archives of general psychiatry.

[24]  Karl J. Friston,et al.  Neural responses to salient visual stimuli , 1997, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[25]  P S Goldman-Rakic,et al.  Topographic organization of medial pulvinar connections with the prefrontal cortex in the rhesus monkey , 1997, The Journal of comparative neurology.

[26]  A. Lammertsma,et al.  Simplified Reference Tissue Model for PET Receptor Studies , 1996, NeuroImage.

[27]  M S Buchsbaum,et al.  PET and MRI of the thalamus in never-medicated patients with schizophrenia. , 1996, The American journal of psychiatry.

[28]  K. Young,et al.  Startle and sensorimotor correlates of ventral thalamic dopamine and GABA in rodents , 1995, Neuroreport.

[29]  G. Sedvall,et al.  Chemical brain anatomy in schizophrenia , 1995, The Lancet.

[30]  T Suhara,et al.  Carbon-11-FLB 457: a radioligand for extrastriatal D2 dopamine receptors. , 1995, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[31]  D. Perani,et al.  High-resolution SPECT study of regional cerebral blood flow in drug-free and drug-naive schizophrenic patients. , 1995, The American journal of psychiatry.

[32]  J. Joyce,et al.  Localization of dopamine D3 receptors to mesolimbic and D2 receptors to mesostriatal regions of human forebrain. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[33]  J. Ehrhardt,et al.  Thalamic abnormalities in schizophrenia visualized through magnetic resonance image averaging. , 1994, Science.

[34]  Robert M. Kessler,et al.  Identification of extrastriatal dopamine D2 receptors in post mortem human brain with [125I]epidepride , 1993, Brain Research.

[35]  J. Palacios,et al.  High resolution separation methods for the determination of intact human erythropoiesis stimulating agents. A review. , 2012, Analytica chimica acta.

[36]  B. Pakkenberg,et al.  The volume of the mediodorsal thalamic nucleus in treated and untreated schizophrenics , 1992, Schizophrenia Research.

[37]  W. Günther.  MRI-SPECT and PET-EEG findings on brain dysfunction in schizophrenia , 1992, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[38]  S. Petersen,et al.  The pulvinar and visual salience , 1992, Trends in Neurosciences.

[39]  B. Pakkenberg,et al.  Pronounced reduction of total neuron number in mediodorsal thalamic nucleus and nucleus accumbens in schizophrenics. , 1990, Archives of general psychiatry.

[40]  Bruno Giros,et al.  Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics , 1990, Nature.

[41]  D. LaBerge,et al.  Positron emission tomographic measurements of pulvinar activity during an attention task , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[42]  G Honigfeld,et al.  Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. , 1988, Archives of general psychiatry.

[43]  D L Rosene,et al.  Cingulate cortex of the rhesus monkey: I. Cytoarchitecture and thalamic afferents , 1987, The Journal of comparative neurology.

[44]  D. Pandya,et al.  Cingulate cortex of the rhesus monkey: II. Cortical afferents , 1987, The Journal of comparative neurology.

[45]  M. Mintun,et al.  A quantitative model for the in vivo assessment of drug binding sites with positron emission tomography , 1984, Annals of neurology.

[46]  U. Ungerstedt.  Stereotaxic mapping of the monoamine pathways in the rat brain. , 1971, Acta physiologica Scandinavica. Supplementum.

[47]  G Mann,et al.  ON THE THALAMUS * , 1905, British medical journal.

[48]  S. Tanada,et al.  Decreased dopamine D2 receptor binding in the anterior cingulate cortex in schizophrenia. , 2002, Archives of general psychiatry.

[49]  William Byne,et al.  Postmortem assessment of thalamic nuclear volumes in subjects with schizophrenia. , 2002, The American journal of psychiatry.

[50]  K. Blennow,et al.  Reduction of the synaptic protein rab3a in the thalamus and connecting brain regions in post-mortem schizophrenic brains , 2000, Journal of Neural Transmission.

[51]  D L Hill,et al.  Automated three-dimensional registration of magnetic resonance and positron emission tomography brain images by multiresolution optimization of voxel similarity measures. , 1997, Medical physics.

[52]  E G Jones,et al.  Cortical development and thalamic pathology in schizophrenia. , 1997, Schizophrenia bulletin.

[53]  D R Medoff,et al.  Functional sites of neuroleptic drug action in the human brain: PET/FDG studies with and without haloperidol. , 1996, The American journal of psychiatry.

[54]  Karl J. Friston,et al.  Statistical parametric maps in functional imaging: A general linear approach , 1994 .

[55]  J. Ehrhardt,et al.  Magnetic resonance imaging of the brain in schizophrenia. The pathophysiologic significance of structural abnormalities. , 1990, Archives of general psychiatry.

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