Striatal dopamine transporter availability is associated with the productive psychotic state in first episode, drug–naive schizophrenic patients

ObjectiveSupposing a "hyperdopaminergic State" associated at least with acute psychotic illness phases in schizophrenia, a direct relationship between striatal dopamine metabolism and the core psychopathological symptoms rarely can be provided. Recently, a new SPECT ligand to the presynaptic dopamine transporter (DAT) was introduced. Association of DAT availability and the acute psychotic syndrome is now demonstrated in a large cohort of first episode, never treated schizophrenic patients.MethodsTwenty–eight inpatients suffering from a first acute exacerbation of schizophrenia and 12 healthy control subjects underwent SPECT scanning with the new radioligand [99mTc]TRODAT–1. On the day of SPECT, psychopathology was assessed using specific scales including PANSS.ResultsThere was no significant difference in [99mTc]TRODAT–1 specific binding to the striatal DAT comparing both groups. The extend of hallucinations was significantly inversely correlated with DAT availability in patients with a predominantly positive syndrome type.DiscussionOur data support evidence that differences in presynaptic dopaminergic activity in schizophrenic patients are associated with the extend of the acute psychotic syndrome. [99mTc]TRODAT–1 seems to be a useful agent for in vivo assessment of a psychopathological association with dopamine metabolism.

[1]  Richard P. Bentall,et al.  Sensory Deception: A Scientific Analysis Of Hallucination , 1988 .

[2]  P. Halligan,et al.  Cognitive neuropsychiatry: towards a scientific psychopathology , 2001, Nature Reviews Neuroscience.

[3]  Michael J Brammer,et al.  Engagement of brain areas implicated in processing inner speech in people with auditory hallucinations. , 2003, The British journal of psychiatry : the journal of mental science.

[4]  S. Kay,et al.  The positive and negative syndrome scale (PANSS) for schizophrenia. , 1987, Schizophrenia bulletin.

[5]  M. Bergström,et al.  Increased dopamine synthesis rate in medial prefrontal cortex and striatum in schizophrenia indicated by L-(β-11C) DOPA and PET , 1999, Biological Psychiatry.

[6]  A Carlsson,et al.  Interactions between monoamines, glutamate, and GABA in schizophrenia: new evidence. , 2001, Annual review of pharmacology and toxicology.

[7]  R. Murray,et al.  The Neural Correlates of Inner Speech and Auditory Verbal Imagery in Schizophrenia: Relationship to Auditory Verbal Hallucinations , 1996, British Journal of Psychiatry.

[8]  P. Kao,et al.  The optimal imaging time for [99Tcm]TRODAT-1/SPET in normal subjects and patients with Parkinson's disease , 2001, Nuclear medicine communications.

[9]  C. Crouzel,et al.  Presynaptic dopaminergic function in the striatum of schizophrenic patients , 1997, Schizophrenia Research.

[10]  C. D. Frith,et al.  Abnormal monitoring of inner speech: a physiological basis for auditory hallucinations , 1995, The Lancet.

[11]  Merja Haaparanta,et al.  Decreased striatal dopamine transporter binding in vivo in chronic schizophrenia , 2001, Schizophrenia Research.

[12]  J. Krystal,et al.  Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort. , 1998, The American journal of psychiatry.

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

[14]  H. Kung,et al.  Pharmacological effects of dopaminergic drugs on in vivo binding of [99mTc]TRODAT-1 to the central dopamine transporters in rats , 1997, European Journal of Nuclear Medicine.

[15]  M. Laruelle,et al.  Increased dopamine transmission in schizophrenia: relationship to illness phases , 1999, Biological Psychiatry.

[16]  Christian la Fougere,et al.  The dopamine transporter and neuroimaging in attention deficit hyperactivity disorder , 2003, Neuroscience & Biobehavioral Reviews.

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

[18]  H. Kung,et al.  Simultaneous SPECT studies of pre- and postsynaptic dopamine binding sites in baboons. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[19]  J. Hietala,et al.  Presynaptic dopamine function in striatum of neuroleptic-naive schizophrenic patients , 1995, The Lancet.

[20]  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.

[21]  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.

[22]  A. Alavi,et al.  Biodistribution and dosimetry of TRODAT-1: a technetium-99m tropane for imaging dopamine transporters. , 1998, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[23]  G. Egan,et al.  Cortical activation associated with the experience of auditory hallucinations and perception of human speech in schizophrenia: a PET correlation study , 2003, Psychiatry Research: Neuroimaging.

[24]  S. Kushner,et al.  Specificity of diastereomers of [99mTc]TRODAT-1 as dopamine transporter imaging agents. , 1998, Journal of medicinal chemistry.

[25]  Philip K McGuire,et al.  Verbal self-monitoring and auditory hallucinations in schizophrenia , 1999, The Lancet.

[26]  Marc Laruelle,et al.  Imaging D2 Receptor Occupancy by Endogenous Dopamine in Humans , 1997, Neuropsychopharmacology.

[27]  K. Tatsch,et al.  Attention deficit hyperactivity disorder: binding of [99mTc]TRODAT-1 to the dopamine transporter before and after methylphenidate treatment , 2000, European Journal of Nuclear Medicine.

[28]  Development of Tc-99m labeled tropanes: TRODAT-1, as a dopamine transporter imaging agent. , 2001, Nuclear medicine and biology.

[29]  M Laruelle,et al.  Alterations of benzodiazepine receptors in type II alcoholic subjects measured with SPECT and [123I]iomazenil. , 1998, The American journal of psychiatry.

[30]  A. Malhotra,et al.  Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[31]  A. Alavi,et al.  Binding of [99mTc]TRODAT-1 to dopamine transporters in patients with Parkinson's disease and in healthy volunteers. , 2000, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[32]  S. Hersch,et al.  The dopamine transporter: immunochemical characterization and localization in brain , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[33]  Edson Amaro,et al.  Temporal course of auditory hallucinations. , 2004, The British journal of psychiatry : the journal of mental science.

[34]  Richard S. J. Frackowiak,et al.  A functional neuroanatomy of hallucinations in schizophrenia , 1995, Nature.

[35]  T. Yen,et al.  Differential diagnosis of Parkinson's disease and vascular parkinsonism by (99m)Tc-TRODAT-1. , 2001, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[36]  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.

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

[38]  S. Kushner,et al.  Synthesis and characterization of technetium-99m-labeled tropanes as dopamine transporter-imaging agents. , 1997, Journal of medicinal chemistry.

[39]  D. Hubl,et al.  Pathways that make voices: white matter changes in auditory hallucinations. , 2004, Archives of general psychiatry.

[40]  Alan C. Evans,et al.  Elevated dopa decarboxylase activity in living brain of patients with psychosis. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[41]  R. Murray,et al.  Functional anatomy of auditory verbal imagery in schizophrenic patients with auditory hallucinations. , 2000, The American journal of psychiatry.

[42]  Klaus Tatsch,et al.  Increased striatal dopamine transporter in adult patients with attention deficit hyperactivity disorder: effects of methylphenidate as measured by single photon emission computed tomography , 2000, Neuroscience Letters.

[43]  R. Murray,et al.  Mapping auditory hallucinations in schizophrenia using functional magnetic resonance imaging. , 2000, Archives of general psychiatry.