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

• Published in: Molecular psychiatry Vol. 27; no. 2; pp. 1233 - 1240
• Main Authors: Plavén-Sigray, Pontus, Ikonen Victorsson, Pauliina, Santillo, Alexander, Matheson, Granville J., Lee, Maria, Collste, Karin, Fatouros-Bergman, Helena, Sellgren, Carl M., Erhardt, Sophie, Agartz, Ingrid, Halldin, Christer, Farde, Lars, Cervenka, Simon
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2022; Nature Publishing Group
• Subjects: 59/57; 59/78; 631/45; 692/699/476/1799; Anisotropy; Antipsychotic Agents - therapeutic use; Antipsychotics; Bayes Theorem; Bayesian analysis; Behavioral Sciences; Biological Psychology; Clinical Medicine; Cortex (frontal); Diffusion Tensor Imaging; Dopamine; Dopamine - metabolism; Dopamine D2 receptors; Genetic analysis; Humans; Klinisk medicin; Magnetic resonance imaging; Medical and Health Sciences; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Mental disorders; Meta-analysis; Neural networks; Neuroimaging; Neurologi; Neurology; Neurosciences; Neurotransmission; Pharmacotherapy; Positron emission tomography; Positron-Emission Tomography - methods; Psychiatry; Psychosis; Psychotic Disorders - metabolism; Psychotropic drugs; Psykiatri; Receptors, Dopamine D3 - metabolism; Schizophrenia; Schizophrenia - metabolism; Thalamus; Thalamus - metabolism
• ISSN: 1359-4184; 1476-5578; 1476-5578
• DOI: 10.1038/s41380-021-01349-x

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 [ 11 C]FLB457. The main outcome was D2-R binding potential (BP ND ) 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 ND 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.