Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.
Brain Health Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Sci Rep. 2023 Mar 27;13(1):4970. doi: 10.1038/s41598-023-31327-y.
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 [F]FEPPA, and blood samples for measurement of cortisol. [F]FEPPA V was non-significantly elevated (6.5-30%) in fronto-limbic regions in PTSD participants. [F]FEPPA V 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 [F]FEPPA V. Average fronto-limbic [F]FEPPA V 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.
小胶质细胞是一种免疫脑细胞,与包括创伤后应激障碍(PTSD)在内的与应激相关的精神疾病有关。它们在 PTSD 的病理生理学以及调节应激的神经生物学系统中的作用尚不完全清楚。我们检验了这样一个假设,即在与 PTSD 相关的额-边缘大脑区域中,小胶质细胞的激活会在与职业相关的 PTSD 患者中升高。我们还探讨了皮质醇与小胶质细胞激活之间的关系。20 名 PTSD 患者和 23 名健康对照者(HC)完成了正电子发射断层扫描(PET)扫描,使用探针[F]FEPPA 对 18kDa 转位蛋白(TSPO)进行了小胶质细胞激活的检测,同时采集了血液样本以测量皮质醇。在 PTSD 患者中,额-边缘区域的[F]FEPPA V 升高(6.5-30%),但无统计学意义。与 PTSD 非使用者相比,报告经常使用大麻的 PTSD 患者的[F]FEPPA V 显著升高(44%,p=0.047)。PTSD 男性患者(21%,p=0.094)和童年早期创伤史(33%,p=0.116)的[F]FEPPA V 升高无统计学意义。仅在 PTSD 组中,平均额-边缘[F]FEPPA V 与皮质醇呈正相关(r=0.530,p=0.028)。尽管我们没有发现 PTSD 患者中 TSPO 结合存在明显异常,但结果表明,小胶质细胞激活可能发生在报告经常使用大麻的亚组中。皮质醇与 TSPO 结合之间的关系表明,下丘脑-垂体-肾上腺轴失调与创伤后的中枢免疫反应之间可能存在联系,这值得进一步研究。