Brasanac Jelena, Hetzer Stefan, Asseyer Susanna, Kuchling Joseph, Bellmann-Strobl Judith, Ritter Kristin, Gamradt Stefanie, Scheel Michael, Haynes John-Dylan, Brandt Alexander U, Paul Friedemann, Gold Stefan M, Weygandt Martin
Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, NeuroCure Clinical Research Center, 10117 Berlin, Germany.
Department of Psychiatry and Psychotherapy, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Campus Benjamin Franklin, 12203 Berlin, Germany.
Brain Commun. 2022 Apr 4;4(2):fcac086. doi: 10.1093/braincomms/fcac086. eCollection 2022.
Epidemiological, clinical and neuroscientific studies support a link between psychobiological stress and multiple sclerosis. Neuroimaging suggests that blunted central stress processing goes along with higher multiple sclerosis severity, neuroendocrine studies suggest that blunted immune system sensitivity to stress hormones is linked to stronger neuroinflammation. Until now, however, no effort has been made to elucidate whether central stress processing and immune system sensitivity to stress hormones are related in a disease-specific fashion, and if so, whether this relation is clinically meaningful. Consequently, we conducted two functional MRI analyses based on a total of 39 persons with multiple sclerosis and 25 healthy persons. Motivated by findings of an altered interplay between neuroendocrine stress processing and T-cell glucocorticoid sensitivity in multiple sclerosis, we searched for neural networks whose stress task-evoked activity is differentially linked to peripheral T-cell glucocorticoid signalling in patients versus healthy persons as a potential indicator of disease-specific CNS-immune crosstalk. Subsequently, we tested whether this activity is simultaneously related to disease severity. We found that activity of a network comprising right anterior insula, right fusiform gyrus, left midcingulate and lingual gyrus was differentially coupled to T-cell glucocorticoid signalling across groups. This network's activity was simultaneously linked to patients' lesion volume, clinical disability and information-processing speed. Complementary analyses revealed that T-cell glucocorticoid signalling was not directly linked to disease severity. Our findings show that alterations in the coupling between central stress processing and T-cell stress hormone sensitivity are related to key severity measures of multiple sclerosis.
流行病学、临床和神经科学研究支持心理生物学应激与多发性硬化症之间存在联系。神经影像学研究表明，中枢应激处理功能减弱与更高的多发性硬化症严重程度相关，神经内分泌研究表明，免疫系统对应激激素的敏感性降低与更强的神经炎症有关。然而，到目前为止，尚未有人努力阐明中枢应激处理和免疫系统对应激激素的敏感性是否以疾病特异性方式相关，如果是，这种关系在临床上是否有意义。因此，我们对总共39名多发性硬化症患者和25名健康人进行了两项功能磁共振成像分析。受多发性硬化症中神经内分泌应激处理与T细胞糖皮质激素敏感性之间相互作用改变的研究结果启发，我们寻找了这样的神经网络，其应激任务诱发的活动在患者与健康人之间与外周T细胞糖皮质激素信号传导有差异关联，以此作为疾病特异性中枢神经系统-免疫相互作用的潜在指标。随后，我们测试了这种活动是否同时与疾病严重程度相关。我们发现，一个由右侧前岛叶、右侧梭状回、左侧中央扣带回和舌回组成的神经网络的活动在不同组之间与T细胞糖皮质激素信号传导有差异耦合。该神经网络的活动同时与患者的病灶体积、临床残疾程度和信息处理速度相关。补充分析表明，T细胞糖皮质激素信号传导与疾病严重程度没有直接关联。我们的研究结果表明，中枢应激处理与T细胞应激激素敏感性之间耦合的改变与多发性硬化症的关键严重程度指标相关。
