Investigating TSPO levels in occupation-related posttraumatic stress disorder

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 V_T was non-significantly elevated (6.5-30%) in fronto-limbic regions in PTSD participants. [¹⁸F]FEPPA V_T 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 V_T. Average fronto-limbic [¹⁸F]FEPPA V_T 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.

Figure 1

Group differences in [¹⁸F]FEPPA V_T. [¹⁸F]FEPPA V_T scatterplot between PTSD (n = 8 HABs [solid]/9 MABs [outline]) and Healthy Controls (HC) (n = 12 HABs [solid]/10 MABs [outline]). RM ANCOVA controlling for genotype and age revealed no main effect of group (F_(1,35) = 1.123, p = 0.297) and a marginal ROI × Group interaction (F_{(2.645,92.571)} = 1.954, p = 0.134). Pairwise comparisons: Insula (6.5% difference, p = 0.596); Hippocampus (12% difference, p = 0.279); Amygdala (30% difference, p = 0.107); PFC (16% difference, p = 0.406); Striatum (22% difference, p = 0.328); and ACC (15% difference, p = 0.356).

Figure 2

[¹⁸F]FEPPA V_T and cannabis use. [¹⁸F]FEPPA V_T between PTSD participants who regularly consume cannabis (n = 3 HABs [solid]/n = 3 MABs [outline]) and PTSD participants who are non-cannabis users (n = 5 HABs [solid]/n = 6 MABs [outline]). PTSD cannabis users have 41.6% higher TSPO binding compared to PTSD participants who do not use cannabis (F_(1,14) = 4.759, p = 0.047).

Figure 3

Relationship between cortisol and [¹⁸F] FEPPA V_T. Higher serum cortisol concentrations (nmol/L) was correlated (r = 0.530, p = 0.028) with higher [¹⁸F] FEPPA V_T in PTSD participants (n = 16).