PET radioligand binding to translocator protein (TSPO) is increased in unmedicated depressed subjects

Erica M. Richards, Paolo Zanotti-Fregonara, Masahiro Fujita, Laura Newman, Cristan Farmer, Elizabeth D. Ballard, Rodrigo Machado-Vieira, Peixiong Yuan, Mark J. Niciu, Chul Hyoung Lyoo, Ioline D. Henter, Giacomo Salvadore, Wayne C. Drevets, Hartmuth Kolb, Robert B. Innis, Carlos A. Zarate

Research output: Contribution to journalArticle

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Abstract

Background: Inflammation is associated with major depressive disorder (MDD). Translocator protein 18 kDa (TSPO), a putative biomarker of neuroinflammation, is quantified using positron emission tomography (PET) and 11C-PBR28, a TSPO tracer. We sought to (1) investigate TSPO binding in MDD subjects currently experiencing a major depressive episode, (2) investigate the effects of antidepressants on TSPO binding, and (3) determine the relationship of peripheral and central inflammatory markers to cerebral TSPO binding. Twenty-eight depressed MDD subjects (unmedicated (n = 12) or medicated (n = 16)) and 20 healthy controls (HC) underwent PET imaging using 11C-PBR28. Total distribution volume (VT, proportional to Bmax/Kd) was measured and corrected with the free fraction in plasma (fp). The subgenual prefrontal cortex (sgPFC) and anterior cingulate cortex (ACC) were the primary regions of interest. Peripheral blood samples and cerebrospinal fluid were analyzed to investigate the relationship between TSPO binding and peripheral and central inflammatory markers, including interleukins and neurotrophic factors previously linked to depression. Results: TSPO binding was higher in MDD versus HC in the sgPFC (Cohen’s d = 0.64, p =.038, 95% CI 0.04–1.24) and ACC (d = 0.60, p =.049, 95% CI 0.001–1.21), though these comparisons missed the corrected threshold for statistical significance (α =.025). Exploratory analyses demonstrated that unmedicated MDD subjects had the highest level of TSPO binding, followed by medicated MDD subjects, who did not differ from HC. TSPO binding correlated with interleukin-5 in cerebrospinal fluid but with no other central inflammatory markers. Conclusions: This study found a trend towards increased TSPO binding in the brains of MDD subjects, and post hoc analysis extended these findings by demonstrating that this abnormality is significant in unmedicated (but not medicated) MDD subjects.

Original languageEnglish
Article number57
JournalEJNMMI Research
Volume8
DOIs
Publication statusPublished - 2018 Jan 1

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Major Depressive Disorder
Protein Binding
Positron-Emission Tomography
Proteins
Gyrus Cinguli
Prefrontal Cortex
Cerebrospinal Fluid
Interleukins
Interleukin-5
Nerve Growth Factors
Antidepressive Agents
Biomarkers
Depression
Inflammation
Brain

All Science Journal Classification (ASJC) codes

  • Radiology Nuclear Medicine and imaging

Cite this

Richards, E. M., Zanotti-Fregonara, P., Fujita, M., Newman, L., Farmer, C., Ballard, E. D., ... Zarate, C. A. (2018). PET radioligand binding to translocator protein (TSPO) is increased in unmedicated depressed subjects. EJNMMI Research, 8, [57]. https://doi.org/10.1186/s13550-018-0401-9
Richards, Erica M. ; Zanotti-Fregonara, Paolo ; Fujita, Masahiro ; Newman, Laura ; Farmer, Cristan ; Ballard, Elizabeth D. ; Machado-Vieira, Rodrigo ; Yuan, Peixiong ; Niciu, Mark J. ; Lyoo, Chul Hyoung ; Henter, Ioline D. ; Salvadore, Giacomo ; Drevets, Wayne C. ; Kolb, Hartmuth ; Innis, Robert B. ; Zarate, Carlos A. / PET radioligand binding to translocator protein (TSPO) is increased in unmedicated depressed subjects. In: EJNMMI Research. 2018 ; Vol. 8.
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title = "PET radioligand binding to translocator protein (TSPO) is increased in unmedicated depressed subjects",
abstract = "Background: Inflammation is associated with major depressive disorder (MDD). Translocator protein 18 kDa (TSPO), a putative biomarker of neuroinflammation, is quantified using positron emission tomography (PET) and 11C-PBR28, a TSPO tracer. We sought to (1) investigate TSPO binding in MDD subjects currently experiencing a major depressive episode, (2) investigate the effects of antidepressants on TSPO binding, and (3) determine the relationship of peripheral and central inflammatory markers to cerebral TSPO binding. Twenty-eight depressed MDD subjects (unmedicated (n = 12) or medicated (n = 16)) and 20 healthy controls (HC) underwent PET imaging using 11C-PBR28. Total distribution volume (VT, proportional to Bmax/Kd) was measured and corrected with the free fraction in plasma (fp). The subgenual prefrontal cortex (sgPFC) and anterior cingulate cortex (ACC) were the primary regions of interest. Peripheral blood samples and cerebrospinal fluid were analyzed to investigate the relationship between TSPO binding and peripheral and central inflammatory markers, including interleukins and neurotrophic factors previously linked to depression. Results: TSPO binding was higher in MDD versus HC in the sgPFC (Cohen’s d = 0.64, p =.038, 95{\%} CI 0.04–1.24) and ACC (d = 0.60, p =.049, 95{\%} CI 0.001–1.21), though these comparisons missed the corrected threshold for statistical significance (α =.025). Exploratory analyses demonstrated that unmedicated MDD subjects had the highest level of TSPO binding, followed by medicated MDD subjects, who did not differ from HC. TSPO binding correlated with interleukin-5 in cerebrospinal fluid but with no other central inflammatory markers. Conclusions: This study found a trend towards increased TSPO binding in the brains of MDD subjects, and post hoc analysis extended these findings by demonstrating that this abnormality is significant in unmedicated (but not medicated) MDD subjects.",
author = "Richards, {Erica M.} and Paolo Zanotti-Fregonara and Masahiro Fujita and Laura Newman and Cristan Farmer and Ballard, {Elizabeth D.} and Rodrigo Machado-Vieira and Peixiong Yuan and Niciu, {Mark J.} and Lyoo, {Chul Hyoung} and Henter, {Ioline D.} and Giacomo Salvadore and Drevets, {Wayne C.} and Hartmuth Kolb and Innis, {Robert B.} and Zarate, {Carlos A.}",
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Richards, EM, Zanotti-Fregonara, P, Fujita, M, Newman, L, Farmer, C, Ballard, ED, Machado-Vieira, R, Yuan, P, Niciu, MJ, Lyoo, CH, Henter, ID, Salvadore, G, Drevets, WC, Kolb, H, Innis, RB & Zarate, CA 2018, 'PET radioligand binding to translocator protein (TSPO) is increased in unmedicated depressed subjects', EJNMMI Research, vol. 8, 57. https://doi.org/10.1186/s13550-018-0401-9

PET radioligand binding to translocator protein (TSPO) is increased in unmedicated depressed subjects. / Richards, Erica M.; Zanotti-Fregonara, Paolo; Fujita, Masahiro; Newman, Laura; Farmer, Cristan; Ballard, Elizabeth D.; Machado-Vieira, Rodrigo; Yuan, Peixiong; Niciu, Mark J.; Lyoo, Chul Hyoung; Henter, Ioline D.; Salvadore, Giacomo; Drevets, Wayne C.; Kolb, Hartmuth; Innis, Robert B.; Zarate, Carlos A.

In: EJNMMI Research, Vol. 8, 57, 01.01.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - PET radioligand binding to translocator protein (TSPO) is increased in unmedicated depressed subjects

AU - Richards, Erica M.

AU - Zanotti-Fregonara, Paolo

AU - Fujita, Masahiro

AU - Newman, Laura

AU - Farmer, Cristan

AU - Ballard, Elizabeth D.

AU - Machado-Vieira, Rodrigo

AU - Yuan, Peixiong

AU - Niciu, Mark J.

AU - Lyoo, Chul Hyoung

AU - Henter, Ioline D.

AU - Salvadore, Giacomo

AU - Drevets, Wayne C.

AU - Kolb, Hartmuth

AU - Innis, Robert B.

AU - Zarate, Carlos A.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: Inflammation is associated with major depressive disorder (MDD). Translocator protein 18 kDa (TSPO), a putative biomarker of neuroinflammation, is quantified using positron emission tomography (PET) and 11C-PBR28, a TSPO tracer. We sought to (1) investigate TSPO binding in MDD subjects currently experiencing a major depressive episode, (2) investigate the effects of antidepressants on TSPO binding, and (3) determine the relationship of peripheral and central inflammatory markers to cerebral TSPO binding. Twenty-eight depressed MDD subjects (unmedicated (n = 12) or medicated (n = 16)) and 20 healthy controls (HC) underwent PET imaging using 11C-PBR28. Total distribution volume (VT, proportional to Bmax/Kd) was measured and corrected with the free fraction in plasma (fp). The subgenual prefrontal cortex (sgPFC) and anterior cingulate cortex (ACC) were the primary regions of interest. Peripheral blood samples and cerebrospinal fluid were analyzed to investigate the relationship between TSPO binding and peripheral and central inflammatory markers, including interleukins and neurotrophic factors previously linked to depression. Results: TSPO binding was higher in MDD versus HC in the sgPFC (Cohen’s d = 0.64, p =.038, 95% CI 0.04–1.24) and ACC (d = 0.60, p =.049, 95% CI 0.001–1.21), though these comparisons missed the corrected threshold for statistical significance (α =.025). Exploratory analyses demonstrated that unmedicated MDD subjects had the highest level of TSPO binding, followed by medicated MDD subjects, who did not differ from HC. TSPO binding correlated with interleukin-5 in cerebrospinal fluid but with no other central inflammatory markers. Conclusions: This study found a trend towards increased TSPO binding in the brains of MDD subjects, and post hoc analysis extended these findings by demonstrating that this abnormality is significant in unmedicated (but not medicated) MDD subjects.

AB - Background: Inflammation is associated with major depressive disorder (MDD). Translocator protein 18 kDa (TSPO), a putative biomarker of neuroinflammation, is quantified using positron emission tomography (PET) and 11C-PBR28, a TSPO tracer. We sought to (1) investigate TSPO binding in MDD subjects currently experiencing a major depressive episode, (2) investigate the effects of antidepressants on TSPO binding, and (3) determine the relationship of peripheral and central inflammatory markers to cerebral TSPO binding. Twenty-eight depressed MDD subjects (unmedicated (n = 12) or medicated (n = 16)) and 20 healthy controls (HC) underwent PET imaging using 11C-PBR28. Total distribution volume (VT, proportional to Bmax/Kd) was measured and corrected with the free fraction in plasma (fp). The subgenual prefrontal cortex (sgPFC) and anterior cingulate cortex (ACC) were the primary regions of interest. Peripheral blood samples and cerebrospinal fluid were analyzed to investigate the relationship between TSPO binding and peripheral and central inflammatory markers, including interleukins and neurotrophic factors previously linked to depression. Results: TSPO binding was higher in MDD versus HC in the sgPFC (Cohen’s d = 0.64, p =.038, 95% CI 0.04–1.24) and ACC (d = 0.60, p =.049, 95% CI 0.001–1.21), though these comparisons missed the corrected threshold for statistical significance (α =.025). Exploratory analyses demonstrated that unmedicated MDD subjects had the highest level of TSPO binding, followed by medicated MDD subjects, who did not differ from HC. TSPO binding correlated with interleukin-5 in cerebrospinal fluid but with no other central inflammatory markers. Conclusions: This study found a trend towards increased TSPO binding in the brains of MDD subjects, and post hoc analysis extended these findings by demonstrating that this abnormality is significant in unmedicated (but not medicated) MDD subjects.

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