Thalamic dopamine D2-receptor availability in schizophrenia : a study on antipsychotic-naive patients with first-episode psychosis and a meta-analysis
(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.
(Less)
- author
- organization
- publishing date
- 2022
- 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) > 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 > 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}}, }