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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.
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1 University of Toronto, Institute of Medical Sciences, Toronto, Canada (GRID:grid.17063.33) (ISNI:0000 0001 2157 2938); Centre for Addiction and Mental Health, Brain Health Imaging Centre, Toronto, Canada (GRID:grid.155956.b) (ISNI:0000 0000 8793 5925)
2 The MacDonald Franklin OSI Research Centre, Lawson Health Research Institute, London, Canada (GRID:grid.415847.b) (ISNI:0000 0001 0556 2414); University of Western Ontario, Department of Psychiatry, London, Canada (GRID:grid.39381.30) (ISNI:0000 0004 1936 8884); McMaster University, Department of Psychiatry and Behavioural Neurosciences, Hamilton, Canada (GRID:grid.25073.33) (ISNI:0000 0004 1936 8227); St Joseph’s, London OSI, Parkwood Institute, St. Joseph’s Health Care, London, Canada (GRID:grid.491177.d)
3 Centre for Addiction and Mental Health, Brain Health Imaging Centre, Toronto, Canada (GRID:grid.155956.b) (ISNI:0000 0000 8793 5925); Campbell Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Canada (GRID:grid.155956.b) (ISNI:0000 0000 8793 5925)
4 Centre for Addiction and Mental Health, Brain Health Imaging Centre, Toronto, Canada (GRID:grid.155956.b) (ISNI:0000 0000 8793 5925); Campbell Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Canada (GRID:grid.155956.b) (ISNI:0000 0000 8793 5925); University of Toronto, Department of Psychiatry, Toronto, Canada (GRID:grid.17063.33) (ISNI:0000 0001 2157 2938)
5 University of Toronto, Institute of Medical Sciences, Toronto, Canada (GRID:grid.17063.33) (ISNI:0000 0001 2157 2938); Centre for Addiction and Mental Health, Brain Health Imaging Centre, Toronto, Canada (GRID:grid.155956.b) (ISNI:0000 0000 8793 5925); Campbell Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Canada (GRID:grid.155956.b) (ISNI:0000 0000 8793 5925); University of Toronto, Department of Psychiatry, Toronto, Canada (GRID:grid.17063.33) (ISNI:0000 0001 2157 2938); University of Toronto, Department of Pharmacology and Toxicology, Toronto, Canada (GRID:grid.17063.33) (ISNI:0000 0001 2157 2938)
6 Canadian Forces Health Services, Directorate of Mental Health, Ottawa, Canada (GRID:grid.457399.5) (ISNI:0000 0001 2295 5076); University of Ottawa, Department of Psychiatry, Faculty of Medicine, Ottawa, Canada (GRID:grid.28046.38) (ISNI:0000 0001 2182 2255); Dalhousie University, Department of Psychiatry, Faculty of Medicine, Halifax, Canada (GRID:grid.55602.34) (ISNI:0000 0004 1936 8200)
7 University of Toronto, Faculty of Kinesiology and Physical Education, Toronto, Canada (GRID:grid.17063.33) (ISNI:0000 0001 2157 2938); University of Toronto, David L. MacIntosh Sport Medicine Clinic, Faculty of Kinesiology and Physical Education, Toronto, Canada (GRID:grid.17063.33) (ISNI:0000 0001 2157 2938); Keenan Research Centre for Biomedical Science of St. Michael’s Hospital, Toronto, Canada (GRID:grid.415502.7)
8 University of Toronto, Faculty of Kinesiology and Physical Education, Toronto, Canada (GRID:grid.17063.33) (ISNI:0000 0001 2157 2938); Defence Research and Development Canada, Toronto Research Centre, Toronto, Canada (GRID:grid.1463.0) (ISNI:0000 0001 0692 6582)
9 University of Toronto, Institute of Medical Sciences, Toronto, Canada (GRID:grid.17063.33) (ISNI:0000 0001 2157 2938); Centre for Addiction and Mental Health, Brain Health Imaging Centre, Toronto, Canada (GRID:grid.155956.b) (ISNI:0000 0000 8793 5925); Campbell Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Canada (GRID:grid.155956.b) (ISNI:0000 0000 8793 5925); University of Toronto, Department of Psychiatry, Toronto, Canada (GRID:grid.17063.33) (ISNI:0000 0001 2157 2938)