重度抑郁症中异常小胶质细胞活性的功能和结构关联。
The functional and structural associations of aberrant microglial activity in major depressive disorder.
机构信息
From the Department of Neuroscience, Western University, London, Ont. (Cakmak, Schaefer, Sabesan, Palaniyappan); the Robarts Research Institute, Western University, London, Ont. (Cakmak, Palaniyappan); the Lawson Health Research Institute, London, Ont. (Liu, Poirier, Burhan, St. Lawrence, Théberge, Hicks, Finger, Anazodo); the Department of Medical Biophysics, Western University, London, Ont. (Poirier, Sabesan, St. Lawrence, Théberge, Hicks, Anazodo); the London Health Sciences Centre, London, Ont. (Schaefer, Poolacherla, Palaniyappan); the Department of Psychiatry, Western University, London, Ont. (Burhan, Théberge, Palaniyappan); the Department of Psychiatry, University of Toronto, Toronto, Ont. (Burhan); the Ontario Shores Centre for Mental Health Sciences, Whitby, Ont. (Burhan); the Department of Clinical Neurological Sciences, Western University, London, Ont. (Finger); the Department of Anesthesia and Perioperative Medicine, Western University, London, Ont. (Poolacherla).
From the Department of Neuroscience, Western University, London, Ont. (Cakmak, Schaefer, Sabesan, Palaniyappan); the Robarts Research Institute, Western University, London, Ont. (Cakmak, Palaniyappan); the Lawson Health Research Institute, London, Ont. (Liu, Poirier, Burhan, St. Lawrence, Théberge, Hicks, Finger, Anazodo); the Department of Medical Biophysics, Western University, London, Ont. (Poirier, Sabesan, St. Lawrence, Théberge, Hicks, Anazodo); the London Health Sciences Centre, London, Ont. (Schaefer, Poolacherla, Palaniyappan); the Department of Psychiatry, Western University, London, Ont. (Burhan, Théberge, Palaniyappan); the Department of Psychiatry, University of Toronto, Toronto, Ont. (Burhan); the Ontario Shores Centre for Mental Health Sciences, Whitby, Ont. (Burhan); the Department of Clinical Neurological Sciences, Western University, London, Ont. (Finger); the Department of Anesthesia and Perioperative Medicine, Western University, London, Ont. (Poolacherla)
出版信息
J Psychiatry Neurosci. 2022 Jun 2;47(3):E197-E208. doi: 10.1503/jpn.210124. Print 2022 May-Jun.
BACKGROUND
Major depressive disorder (MDD) is a debilitating mental illness that has been linked to increases in markers of inflammation, as well as to changes in brain functional and structural connectivity, particularly between the insula and the subgenual anterior cingulate cortex (sgACC). In this study, we directly related inflammation and dysconnectivity in treatment-resistant MDD by concurrently measuring the following: microglial activity with [F]N-2-(fluoroethoxyl)benzyl-N-(4phenoxypyridin-3-yl)acetamide ([F]FEPPA) positron emission tomography (PET); the severity of MDD; and functional or structural connectivity among insula or sgACC nodes.
METHODS
Twelve patients with treatment-resistant MDD (8 female, 4 male; mean age ± standard deviation 54.9 ± 4.5 years and 23 healthy controls (11 female, 12 male; 60.3 ± 8.5 years) completed a hybrid [F]FEPPA PET and MRI acquisition. From these, we extracted relative standardized uptake values for [F]FEPPA activity and Pearson -to- scores representing functional connectivity from our regions of interest. We extracted diffusion tensor imaging metrics from the cingulum bundle, a key white matter bundle in MDD. We performed regressions to relate microglial activity with functional connectivity, structural connectivity and scores on the 17-item Hamilton Depression Rating Scale.
RESULTS
We found significantly increased [F]FEPPA uptake in the left sgACC in patients with treatment-resistant MDD compared to healthy controls. Patients with MDD also had a reduction in connectivity between the sgACC and the insula. The [F]FEPPA uptake in the left sgACC was significantly related to functional connectivity with the insula, and to the structural connectivity of the cingulum bundle. [F]FEPPA uptake also predicted scores on the Hamilton Depression Rating Scale. A relatively small sample size, lack of functional task data and concomitant medication use may have affected our findings.
CONCLUSION
We present preliminary evidence linking a network-level dysfunction relevant to the pathophysiology of depression and related to increased microglial activity in MDD.
背景
重度抑郁症（MDD）是一种使人虚弱的精神疾病，它与炎症标志物的增加以及大脑功能和结构连接的变化有关，特别是在岛叶和前扣带皮层亚属（sgACC）之间。在这项研究中，我们通过同时测量以下指标，直接将治疗抵抗性 MDD 中的炎症和功能障碍联系起来：使用 [F]N-2-（氟乙氧基）苯甲基-N-（4-苯氧基吡啶-3-基）乙酰胺（[F]FEPPA）正电子发射断层扫描（PET）测量小胶质细胞活性；MDD 的严重程度；以及岛叶或 sgACC 节点之间的功能或结构连接。
方法
12 名治疗抵抗性 MDD 患者（8 名女性，4 名男性；平均年龄±标准差 54.9±4.5 岁和 23 名健康对照组（11 名女性，12 名男性；60.3±8.5 岁）完成了混合 [F]FEPPA PET 和 MRI 采集。从这些数据中，我们从我们的感兴趣区域中提取了 [F]FEPPA 活性的相对标准化摄取值和表示功能连接的 Pearson 相关分数。我们从扣带束中提取了弥散张量成像指标，这是 MDD 中的一个关键白质束。我们进行了回归分析，将小胶质细胞活性与功能连接、结构连接和 17 项汉密尔顿抑郁评定量表的分数联系起来。
结果
与健康对照组相比，治疗抵抗性 MDD 患者的左侧 sgACC 中 [F]FEPPA 摄取明显增加。MDD 患者的 sgACC 与岛叶之间的连接也减少了。左侧 sgACC 的 [F]FEPPA 摄取与与岛叶的功能连接显著相关，并且与扣带束的结构连接相关。[F]FEPPA 摄取也预测了汉密尔顿抑郁评定量表的分数。样本量较小、缺乏功能任务数据和同时使用药物可能影响了我们的发现。
结论
我们提出了初步证据，将与抑郁病理生理学相关的网络级功能障碍与 MDD 中小胶质细胞活性增加联系起来。
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