Decreased thalamic D2/D3 receptor binding in drug-naive patients with schizophrenia: a PET study with [11C]FLB 457

Int J Neuropsychopharmacol. 2003 Dec;6(4):361-70. doi: 10.1017/S1461145703003699.

Abstract

The thalamus is a neuroanatomic structure that has reciprocal connections with several brain regions suggested to be involved in the pathophysiology of schizophrenia. Recent studies have reported structural as well as functional abnormalities of the thalamus in schizophrenia. The aim of the present exploratory study was to examine D2/D3 dopamine receptors in the thalamus as well as the anterior cingulate and the frontal and temporal cortices by using the high-affinity radioligand [11C]FLB 457 and positron emission tomography (3D PET) and to explore the data in relation to disease, age and psychopathology. Nine drug-naive patients with schizophrenia and eight control subjects were examined. Regional binding potential (BP) values were calculated using the simplified reference tissue model. The D2/D3 receptor binding was significantly lower in the right medial thalamus in the schizophrenia patients compared to control subjects. In addition, we found a significant negative age effect on the D2/D3 BP in the frontal and temporal cortex for both groups. There was no significant age effect on the D2/D3 BP in the thalamus or in the anterior cingulate. The result provides additional support to the view that the age effect on D2/D3 receptors differ between brain regions. The preliminary finding of low thalamic D2/D3 BP in patients strengthens the hypothesis that the thalamus is a key region in the pathophysiology of schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain Mapping
  • Carbon Radioisotopes* / pharmacokinetics
  • Dopamine Antagonists* / pharmacokinetics
  • Female
  • Frontal Lobe / diagnostic imaging
  • Frontal Lobe / physiopathology
  • Gyrus Cinguli / diagnostic imaging
  • Gyrus Cinguli / physiopathology
  • Humans
  • Male
  • Middle Aged
  • Psychiatric Status Rating Scales
  • Pyrrolidines* / pharmacokinetics
  • Receptors, Dopamine D2 / physiology*
  • Receptors, Dopamine D3
  • Reference Values
  • Salicylamides* / pharmacokinetics
  • Schizophrenia, Paranoid / diagnostic imaging*
  • Schizophrenia, Paranoid / physiopathology
  • Temporal Lobe / diagnostic imaging
  • Temporal Lobe / physiopathology
  • Thalamus / diagnostic imaging*
  • Thalamus / physiopathology
  • Tomography, Emission-Computed*

Substances

  • Carbon Radioisotopes
  • DRD3 protein, human
  • Dopamine Antagonists
  • Pyrrolidines
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3
  • Salicylamides
  • FLB 457