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

Plavén-Sigray, Pontus ; Ikonen Victorsson, Pauliina ; Santillo, Alexander LU orcid ; Matheson, Granville J. ; Lee, Maria ; Collste, Karin ; Fatouros-Bergman, Helena ; Sellgren, Carl M. ; Erhardt, Sophie and Agartz, Ingrid , et al. (2022) In Molecular Psychiatry 27(2). p.1233-1240
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Psychiatry
volume
27
issue
2
pages
1233 - 1240
publisher
Nature Publishing Group
external identifiers
  • pmid:34759359
  • scopus:85118891942
ISSN
1359-4184
DOI
10.1038/s41380-021-01349-x
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2021, The Author(s).
id
fe1bb843-4ba0-4cfc-b52b-b95ae3f2801b
date added to LUP
2021-12-02 15:44:00
date last changed
2024-04-06 14:28:37
@article{fe1bb843-4ba0-4cfc-b52b-b95ae3f2801b,
  abstract     = {{<p>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 [<sup>11</sup>C]FLB457. The main outcome was D2-R binding potential (BP<sub>ND</sub>) 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) &gt; 4). Among subregions, lower BP<sub>ND</sub> was observed in the ROI representing thalamic connectivity to the frontal cortex (Cohen’s dz = −0.527, p = 0.017, BF &gt; 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.</p>}},
  author       = {{Plavén-Sigray, Pontus and Ikonen Victorsson, Pauliina and Santillo, Alexander and Matheson, Granville J. and Lee, Maria and Collste, Karin and Fatouros-Bergman, Helena and Sellgren, Carl M. and Erhardt, Sophie and Agartz, Ingrid and Halldin, Christer and Farde, Lars and Cervenka, Simon}},
  issn         = {{1359-4184}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{1233--1240}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Molecular Psychiatry}},
  title        = {{Thalamic dopamine D2-receptor availability in schizophrenia : a study on antipsychotic-naive patients with first-episode psychosis and a meta-analysis}},
  url          = {{http://dx.doi.org/10.1038/s41380-021-01349-x}},
  doi          = {{10.1038/s41380-021-01349-x}},
  volume       = {{27}},
  year         = {{2022}},
}