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

Authors
 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 Jr 
Citation
 EJNMMI Research, Vol.8 : 57, 2018 
Journal Title
 EJNMMI Research 
Issue Date
2018
Keywords
Biomarkers ; Inflammation ; Major depressive disorder ; Peripheral benzodiazepine receptor ; Positron emission tomography
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.
Files in This Item:
T201803534.pdf Download
DOI
10.1186/s13550-018-0401-9
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
Lyoo, Chul Hyoung(류철형) ORCID logo https://orcid.org/0000-0003-2231-672X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/163762
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