Clausen Mette, Larsen Søren Vinther, Hogsted Emma Sofie, Nasser Arafat, Svarer Claus, Knudsen Gitte Moos, Frokjaer Vibe Gedso
Neurobiology Research Unit, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Neurosci Appl. 2024 Jun 14;3:104078. doi: 10.1016/j.nsa.2024.104078. eCollection 2024.
Inflammatory status affects healthy brain function and also low-grade inflammation putatively contributes to the pathophysiology of Major Depressive Disorder (MDD). This psychoneuro-immunological interplay is complex, bidirectional, and not fully understood. Also, it is not clear to what extent depressive states induce inflammation and/or if increased inflammation leads to depressive symptoms by affecting brain biology including serotonin signaling. The serotonin 4 receptor (5-HTR) is an interesting new antidepressant target; direct stimulation has antidepressant-like, and pro-cognitive effects, and may also index serotonin tone at least in the adult healthy brain. Here, we investigate whether a peripheral marker of low-grade inflammation (hsCRP) is associated with 5-HTR brain binding in both a healthy and in an unmedicated MDD group. 5-HTR PET imaging data and hsCRP measures from 112 healthy and 79 unmedicated MDD individuals were available from the Cimbi database. We evaluated the associations between hsCRP level and 5-HTR binding in three regions of interest (neocortex, hippocampus, and neostriatum) using multiple linear regression models adjusted for relevant covariates. We did not observe a statistically significant association between hsCRP and 5-HTR binding. This applied to both the healthy and the MDD group. Our findings do support a coupling between low-grade inflammation and brain 5-HTR availability, which suggests that the serotonergic system is not sensitive to low-grade inflammation captured by hsCRP, neither in healthy nor in depressed states. Future studies are needed to test if the brain serotonin system is coupled to other inflammatory markers, for instance in conditions with high-grade and/or prolonged immunoactivation.
炎症状态会影响健康的大脑功能，低度炎症也被认为在重度抑郁症（MDD）的病理生理学中起作用。这种心理神经免疫学的相互作用是复杂的、双向的，尚未完全被理解。此外，抑郁状态在多大程度上会引发炎症和/或炎症增加是否通过影响包括血清素信号传导在内的大脑生物学而导致抑郁症状尚不清楚。血清素4受体（5-HTR）是一个有趣的新型抗抑郁靶点；直接刺激具有抗抑郁样和促认知作用，并且至少在成年健康大脑中可能还能反映血清素水平。在此，我们研究低度炎症的外周标志物（hsCRP）在健康组和未用药的MDD组中是否与5-HTR脑结合相关。来自Cimbi数据库的112名健康个体和79名未用药的MDD个体的5-HTR PET成像数据和hsCRP测量值可供使用。我们使用针对相关协变量进行调整的多元线性回归模型，评估了hsCRP水平与三个感兴趣区域（新皮层、海马体和新纹状体）中5-HTR结合之间的关联。我们未观察到hsCRP与5-HTR结合之间存在统计学上的显著关联。这适用于健康组和MDD组。我们的研究结果确实支持低度炎症与大脑5-HTR可用性之间的关联，这表明血清素能系统对hsCRP所反映的低度炎症不敏感，无论是在健康状态还是抑郁状态下。未来需要开展研究来测试大脑血清素系统是否与其他炎症标志物相关联，例如在高度和/或长期免疫激活的情况下。
