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Investigating TSPO levels in occupation-related posttraumatic stress disorder
Sarah E Watling1,2, Talwinder Gill1,2, Erin V Gaudette1,2
1Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.
Abstract:
Microglia are immune brain cells implicated in stress-related mental illnesses including posttraumatic stress disorder (PTSD). Their role in the pathophysiology of PTSD, and on neurobiological systems that regulate stress, is not completely understood. We tested the hypothesis that microglia activation, in fronto-limbic brain regions involved in PTSD, would be elevated in participants with occupation-related PTSD. We also explored the relationship between cortisol and microglia activation. Twenty participants with PTSD and 23 healthy controls (HC) completed positron emission tomography (PET) scanning of the 18-kDa translocator protein (TSPO), a putative biomarker of microglia activation using the probe [18F]FEPPA, and blood samples for measurement of cortisol. [18F]FEPPA VT was non-significantly elevated (6.5-30%) in fronto-limbic regions in PTSD participants. [18F]FEPPA VT was significantly higher in PTSD participants reporting frequent cannabis use compared to PTSD non-users (44%, p = 0.047). Male participants with PTSD (21%, p = 0.094) and a history of early childhood trauma (33%, p = 0.116) had non-significantly higher [18F]FEPPA VT. Average fronto-limbic [18F]FEPPA VT was positively related to cortisol (r = 0.530, p = 0.028) in the PTSD group only. Although we did not find a significant abnormality in TSPO binding in PTSD, findings suggest microglial activation might have occurred in a subgroup who reported frequent cannabis use. The relationship between cortisol and TSPO binding suggests a potential link between hypothalamic-pituitary-adrenal-axis dysregulation and central immune response to trauma which warrants further study.
Insights
Microglia activation in the brain may be linked to posttraumatic stress disorder (PTSD). Findings suggest a connection between cortisol levels and immune response in PTSD, particularly in those with a history of cannabis use.
Area of Science:
- Neuroscience
- Psychiatry
- Immunology
Background:
- Microglia, the brain's immune cells, are increasingly implicated in stress-related mental illnesses like PTSD.
- The precise role of microglia in PTSD pathophysiology and stress regulation remains unclear.
Purpose of the Study:
- To investigate elevated microglia activation in fronto-limbic regions of individuals with occupation-related PTSD.
- To explore the relationship between cortisol levels and microglia activation in PTSD.
Main Methods:
- Positron emission tomography (PET) scanning using the [18F]FEPPA probe to measure 18-kDa translocator protein (TSPO) binding, a marker for microglia activation.
- Blood samples were collected to measure cortisol levels.
- Comparison between 20 PTSD participants and 23 healthy controls (HC).
Main Results:
- Non-significant elevations in [18F]FEPPA V T (microglia activation marker) in fronto-limbic regions of PTSD participants compared to HC.
- Significantly higher [18F]FEPPA V T in PTSD participants who frequently used cannabis.
- A positive correlation between fronto-limbic [18F]FEPPA V T and cortisol levels was observed exclusively in the PTSD group.
Conclusions:
- While overall TSPO binding was not significantly different in PTSD, findings suggest potential microglial activation in a subgroup with frequent cannabis use.
- The correlation between cortisol and TSPO binding indicates a possible link between HPA-axis dysregulation and central immune responses to trauma.
- Further research is warranted to elucidate the complex interplay between trauma, stress hormones, and neuroinflammation in PTSD.
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