Abstract
Background
Gliosis is common among neuropsychiatric diseases, but the relationship between gliosis
and response to therapeutics targeting effects of gliosis is largely unknown. Translocator
protein total distribution volume (TSPO VT), measured with positron emission tomography, mainly reflects gliosis in neuropsychiatric
disease. Here, the primary objective was to determine whether TSPO VT in the prefrontal cortex (PFC) and anterior cingulate cortex (ACC) predicts reduction
of depressive symptoms following open-label celecoxib administration in treatment-resistant
major depressive disorder.
Methods
A total of 41 subjects with treatment-resistant major depressive disorder underwent
one [18F]FEPPA positron emission tomography scan to measure PFC and ACC TSPO VT. Open-label oral celecoxib (200 mg, twice daily) was administered for 8 weeks. Change
in symptoms was measured with the 17-item Hamilton Depression Rating Scale (HDRS).
Results
Cumulative mean change in HDRS scores between 0 and 8 weeks of treatment was plotted
against PFC and ACC TSPO VT, showing a significant nonlinear relationship. At low TSPO VT values, there was no reduction in HDRS scores, but as TSPO VT values increased, there was a reduction in HDRS scores that then plateaued. This
was modeled with a 4-parameter sigmoidal model in which PFC and ACC TSPO VT accounted for 84% and 92% of the variance, respectively.
Conclusions
Celecoxib administration in the presence of gliosis labeled by TSPO VT is associated with greater reduction of symptoms. Given the predictiveness of TSPO
VT on symptom reduction, this personalized medicine approach of matching a marker of
gliosis to medication targeting effects of gliosis should be applied in early development
of novel therapeutics, in particular for treatment-resistant major depressive disorder.
Keywords
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Article info
Publication history
Published online: March 28, 2020
Accepted:
March 11,
2020
Received in revised form:
March 5,
2020
Received:
October 24,
2019
Identification
Copyright
© 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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- Microglial Activation and Response to Anti-inflammatory Treatment in Major Depressive Disorder: Another Piece in the Inflammation–Mood Disorders PuzzleBiological PsychiatryVol. 88Issue 8
- PreviewThere is good news and bad news when it comes to our understanding of inflammation in the pathogenesis and treatment of major depressive disorder (MDD). The bad news is that, like the dexamethasone suppression test or the efficacy of antidepressants before it, inflammation is oversold as an answer to the mystery of depression and its treatment. The good news is that an unusually replicable set of findings (for psychiatry) increasingly paints a consistent picture of the ways in which inflammation is of value in understanding MDD.
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