Thalamic dopamine D2-receptor availability in schizophrenia: a study on antipsychotic-naive patients with first-episode psychosis and a meta-analysis

Pontus Plavén-Sigray, Pauliina Ikonen Victorsson, Alexander Santillo, Granville J Matheson, Maria Lee, Karin Collste, Helena Fatouros-Bergman, Carl M Sellgren, Sophie Erhardt, Ingrid Agartz, Christer Halldin, Lars Farde, Simon Cervenka

Abstract

Pharmacological and genetic evidence support a role for an involvement of the dopamine D2-receptor (D2-R) in the pathophysiology of schizophrenia. Previous molecular imaging studies have suggested lower levels of D2-R in thalamus, but results are inconclusive. The objective of the present study was to use improved methodology to compare D2-R density in whole thalamus and thalamic subregions between first-episode psychosis patients and healthy controls. Differences in thalamocortical connectivity was explored based on the D2-R results. 19 antipsychotic-naive first-episode psychosis patients and 19 age- and sex-matched healthy controls were examined using high-resolution Positron Emission Tomography (PET) and the high-affinity D2-R radioligand [11C]FLB457. The main outcome was D2-R binding potential (BPND) in thalamus, and it was predicted that patients would have lower binding. Diffusion tensor imaging (DTI) was performed in a subgroup of 11 patients and 15 controls. D2-R binding in whole thalamus was lower in patients compared with controls (Cohen's dz = -0.479, p = 0.026, Bayes Factor (BF) > 4). Among subregions, lower BPND was observed in the ROI representing thalamic connectivity to the frontal cortex (Cohen's dz = -0.527, p = 0.017, BF > 6). A meta-analysis, including the sample of this study, confirmed significantly lower thalamic D2-R availability in patients. Exploratory analyses suggested that patients had lower fractional anisotropy values compared with controls (Cohen's d = -0.692, p = 0.036) in the inferior thalamic radiation. The findings support the hypothesis of a dysregulation of thalamic dopaminergic neurotransmission in schizophrenia, and it is hypothesized that this could underlie a disturbance of thalamocortical connectivity.

Original languageEnglish
JournalMolecular Psychiatry
Volume27
Issue number2
Pages (from-to)1233-1240
Number of pages8
ISSN1359-4184
DOIs
Publication statusPublished - Feb 2022

Keywords

  • Antipsychotic Agents/therapeutic use
  • Bayes Theorem
  • Diffusion Tensor Imaging
  • Dopamine/metabolism
  • Humans
  • Positron-Emission Tomography/methods
  • Psychotic Disorders/metabolism
  • Receptors, Dopamine D3/metabolism
  • Schizophrenia/metabolism
  • Thalamus/metabolism

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