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

Am J Psychiatry. 2004 Jun;161(6):1016-22. doi: 10.1176/appi.ajp.161.6.1016.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brief Psychiatric Rating Scale
  • Carbon Radioisotopes / metabolism
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Pyrrolidines / metabolism
  • Radioligand Assay / statistics & numerical data
  • Receptors, Dopamine D2 / metabolism*
  • Salicylamides / metabolism
  • Schizophrenia / diagnosis
  • Schizophrenia / diagnostic imaging
  • Schizophrenia / metabolism*
  • Schizophrenic Psychology
  • Thalamic Nuclei / diagnostic imaging
  • Thalamic Nuclei / metabolism
  • Thalamus / diagnostic imaging
  • Thalamus / metabolism*
  • Tomography, Emission-Computed / statistics & numerical data

Substances

  • Carbon Radioisotopes
  • Pyrrolidines
  • Receptors, Dopamine D2
  • Salicylamides
  • FLB 457