The neuroinflammation marker translocator protein is not elevated in individuals with mild-to-moderate depression: A [11C]PBR28 PET study
•Individuals with mild-to-moderate depression without systemic inflammation do not have neuroinflammation, as measured with PET imaging. Depression is associated with systemic inflammation. In animals, systemic inflammation can induce neuroinflammation and activation of microglia; however, postmorte...
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Published in | Brain, behavior, and immunity Vol. 33; pp. 131 - 138 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Netherlands
Elsevier Inc
01.10.2013
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Subjects | |
Online Access | Get full text |
ISSN | 0889-1591 1090-2139 |
DOI | 10.1016/j.bbi.2013.06.010 |
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Abstract | •Individuals with mild-to-moderate depression without systemic inflammation do not have neuroinflammation, as measured with PET imaging.
Depression is associated with systemic inflammation. In animals, systemic inflammation can induce neuroinflammation and activation of microglia; however, postmortem studies have not convincingly shown that there is neuroinflammation in depression. The purpose of this study was to use positron emission tomography (PET) with [11C]PBR28, which binds to the neuroinflammation marker translocator protein 18kDa (TSPO), to compare the level of TSPO between individuals with depression and control subjects. Ten individuals who were in an acute episode of major depression and 10 control subjects matched for TSPO genotype and other characteristics had a PET scan with arterial input function to quantify levels of TSPO in brain regions of interest (ROIs). Total volume of distribution (VT) of [11C]PBR28 was used as a measure of total ligand binding. The primary outcome was the difference in VT between the two groups; this was assessed using a linear mixed model with group as a between-subject factor and region as a within-subject factor. There was no statistically significant difference in [11C]PBR28 binding (VT) between the two groups. In fact, 7 of 10 individuals with depression had lower [11C]PBR28 binding in all ROIs compared to their respective genotype-matched control subjects. Future studies are needed to determine whether individuals with mild-to-moderate depression have lower TSPO levels and to assess whether individuals with severe depression and/or with elevated levels of systemic inflammation might have higher TSPO levels than control subjects. |
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AbstractList | •Individuals with mild-to-moderate depression without systemic inflammation do not have neuroinflammation, as measured with PET imaging.
Depression is associated with systemic inflammation. In animals, systemic inflammation can induce neuroinflammation and activation of microglia; however, postmortem studies have not convincingly shown that there is neuroinflammation in depression. The purpose of this study was to use positron emission tomography (PET) with [11C]PBR28, which binds to the neuroinflammation marker translocator protein 18kDa (TSPO), to compare the level of TSPO between individuals with depression and control subjects. Ten individuals who were in an acute episode of major depression and 10 control subjects matched for TSPO genotype and other characteristics had a PET scan with arterial input function to quantify levels of TSPO in brain regions of interest (ROIs). Total volume of distribution (VT) of [11C]PBR28 was used as a measure of total ligand binding. The primary outcome was the difference in VT between the two groups; this was assessed using a linear mixed model with group as a between-subject factor and region as a within-subject factor. There was no statistically significant difference in [11C]PBR28 binding (VT) between the two groups. In fact, 7 of 10 individuals with depression had lower [11C]PBR28 binding in all ROIs compared to their respective genotype-matched control subjects. Future studies are needed to determine whether individuals with mild-to-moderate depression have lower TSPO levels and to assess whether individuals with severe depression and/or with elevated levels of systemic inflammation might have higher TSPO levels than control subjects. Depression is associated with systemic inflammation. In animals, systemic inflammation can induce neuroinflammation and activation of microglia; however, postmortem studies have not convincingly shown that there is neuroinflammation in depression. The purpose of this study was to use positron emission tomography (PET) with [ 11 C]PBR28, which binds to the neuroinflammation marker translocator protein 18 kDa (TSPO), to compare the level of TSPO between individuals with depression and control subjects. Ten individuals who were in an acute episode of major depression and 10 control subjects matched for TSPO genotype and other characteristics had a PET scan with arterial input function to quantify levels of TSPO in brain regions of interest (ROIs). Total volume of distribution ( V T ) of [ 11 C]PBR28 was used as a measure of total ligand binding. The primary outcome was the difference in V T between the two groups; this was assessed using a linear mixed model with group as a between-subject factor and region as a within-subject factor. There was no statistically significant difference in [ 11 C]PBR28 binding ( V T ) between the two groups. In fact, 7 of 10 individuals with depression had lower [ 11 C]PBR28 binding in all ROIs compared to their respective genotype-matched control subjects. Future studies are needed to determine whether individuals with mild-to-moderate depression have lower TSPO levels and to assess whether individuals with severe depression and/or with elevated levels of systemic inflammation might have higher TSPO levels than control subjects. Depression is associated with systemic inflammation. In animals, systemic inflammation can induce neuroinflammation and activation of microglia; however, postmortem studies have not convincingly shown that there is neuroinflammation in depression. The purpose of this study was to use positron emission tomography (PET) with [¹¹C]PBR28, which binds to the neuroinflammation marker translocator protein 18 kDa (TSPO), to compare the level of TSPO between individuals with depression and control subjects. Ten individuals who were in an acute episode of major depression and 10 control subjects matched for TSPO genotype and other characteristics had a PET scan with arterial input function to quantify levels of TSPO in brain regions of interest (ROIs). Total volume of distribution (VT) of [¹¹C]PBR28 was used as a measure of total ligand binding. The primary outcome was the difference in VT between the two groups; this was assessed using a linear mixed model with group as a between-subject factor and region as a within-subject factor. There was no statistically significant difference in [¹¹C]PBR28 binding (VT) between the two groups. In fact, 7 of 10 individuals with depression had lower [¹¹C]PBR28 binding in all ROIs compared to their respective genotype-matched control subjects. Future studies are needed to determine whether individuals with mild-to-moderate depression have lower TSPO levels and to assess whether individuals with severe depression and/or with elevated levels of systemic inflammation might have higher TSPO levels than control subjects. Highlight • Individuals with mild-to-moderate depression without systemic inflammation do not have neuroinflammation, as measured with PET imaging. |
Author | Esterlis, Irina Lee, Jae-Yun Carson, Richard E. Hannestad, Jonas O’Connor, Kevin C. Pittman, Brian Pelletier, Daniel DellaGioia, Nicole Lim, Keunpoong Nabulsi, Nabeel Gallezot, Jean-Dominique |
AuthorAffiliation | a Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA c Department of Neurology, Program in Human and Translational Immunology, Yale School of Medicine, New Haven, CT, USA b Department of Diagnostic Radiology, Yale School of Medicine, New Haven, CT, USA |
AuthorAffiliation_xml | – name: a Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA – name: c Department of Neurology, Program in Human and Translational Immunology, Yale School of Medicine, New Haven, CT, USA – name: b Department of Diagnostic Radiology, Yale School of Medicine, New Haven, CT, USA |
Author_xml | – sequence: 1 givenname: Jonas surname: Hannestad fullname: Hannestad, Jonas email: jonas.hannestad@yale.edu organization: Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA – sequence: 2 givenname: Nicole surname: DellaGioia fullname: DellaGioia, Nicole organization: Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA – sequence: 3 givenname: Jean-Dominique surname: Gallezot fullname: Gallezot, Jean-Dominique organization: Department of Diagnostic Radiology, Yale School of Medicine, New Haven, CT, USA – sequence: 4 givenname: Keunpoong surname: Lim fullname: Lim, Keunpoong organization: Department of Diagnostic Radiology, Yale School of Medicine, New Haven, CT, USA – sequence: 5 givenname: Nabeel surname: Nabulsi fullname: Nabulsi, Nabeel organization: Department of Diagnostic Radiology, Yale School of Medicine, New Haven, CT, USA – sequence: 6 givenname: Irina surname: Esterlis fullname: Esterlis, Irina organization: Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA – sequence: 7 givenname: Brian surname: Pittman fullname: Pittman, Brian organization: Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA – sequence: 8 givenname: Jae-Yun surname: Lee fullname: Lee, Jae-Yun organization: Department of Neurology, Program in Human and Translational Immunology, Yale School of Medicine, New Haven, CT, USA – sequence: 9 givenname: Kevin C. surname: O’Connor fullname: O’Connor, Kevin C. organization: Department of Neurology, Program in Human and Translational Immunology, Yale School of Medicine, New Haven, CT, USA – sequence: 10 givenname: Daniel surname: Pelletier fullname: Pelletier, Daniel organization: Department of Diagnostic Radiology, Yale School of Medicine, New Haven, CT, USA – sequence: 11 givenname: Richard E. surname: Carson fullname: Carson, Richard E. organization: Department of Diagnostic Radiology, Yale School of Medicine, New Haven, CT, USA |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/23850810$$D View this record in MEDLINE/PubMed |
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Keywords | Depression Neuroinflammation Translocator protein 18kDa PET Microglia Translocator protein 18 kDa |
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Snippet | •Individuals with mild-to-moderate depression without systemic inflammation do not have neuroinflammation, as measured with PET imaging.
Depression is... Highlight • Individuals with mild-to-moderate depression without systemic inflammation do not have neuroinflammation, as measured with PET imaging. Depression is associated with systemic inflammation. In animals, systemic inflammation can induce neuroinflammation and activation of microglia; however,... |
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SubjectTerms | Adolescent Adult Allergy and Immunology Biomarkers - metabolism C-Reactive Protein - metabolism Carbon Radioisotopes Case-Control Studies Depression Depression - blood Depression - immunology Depression - pathology Female Genotype Humans Magnetic Resonance Imaging Male Microglia Microglia - immunology Microglia - metabolism Microglia - pathology Middle Aged Neurogenic Inflammation - blood Neurogenic Inflammation - immunology Neurogenic Inflammation - pathology Neuroinflammation PET Positron-Emission Tomography - methods Protein Binding - immunology Psychiatry Receptors, GABA - blood Translocator protein 18 kDa Young Adult |
Title | The neuroinflammation marker translocator protein is not elevated in individuals with mild-to-moderate depression: A [11C]PBR28 PET study |
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