Association between peripheral inflammation and free-water imaging in Major Depressive Disorder before and after ketamine treatment - A pilot study.
Association between peripheral inflammation and free-water imaging in Major Depressive Disorder before and after ketamine treatment - A pilot study.
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DOI：
10.1016/j.jad.2022.06.043
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发表时间：
2022-06
影响因子：
6.6
通讯作者：
Mina Langhein;J. Seitz-Holland;A. Lyall;O. Pasternak;Natalia Chunga-Iturry;Suheyla Cetin Karayumak;A. Kubicki;C. Mulert;R. Espinoza;K. Narr;M. Kubicki
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作者：
Mina Langhein;J. Seitz-Holland;A. Lyall;O. Pasternak;Natalia Chunga-Iturry;Suheyla Cetin Karayumak;A. Kubicki;C. Mulert;R. Espinoza;K. Narr;M. Kubicki
背景：严重抑郁障碍(MDD)患者的外周炎性改变和白质(WM)恶化是常见的。本研究应用游离水成像技术，探讨外周炎症改变与白质微结构改变之间的关系及其对MDD患者氯胺酮治疗反应的预测价值。方法对10例MDD患者分别于注射氯胺酮前和注射氯胺酮后24小时进行磁共振扩散加权成像和抽血。我们使用MANCOVA和ANCOVA来比较基线时MDD患者和15名健康对照的组织特异性分数各向异性(脂肪)和扣带回的游离水(FW)，以及促炎IL-8/抗炎IL-10的比率。接下来，我们比较了氯胺酮响应者(6人)和无反应者(4人)之间的所有基线测量，并分析了注射氯胺酮后影像和血液数据的变化。结果MDD组在基线时与对照组相比IL-8/IL-10比值升高(p=4.040)，这与感兴趣区域的平均FW呈正相关(p=0.013)。氯胺酮反应者左侧扣带回的基线脂肪高于无反应者(p=4.023)。氯胺酮输注不影响白质微结构，但降低IL-8/IL-10比值(p=0.043)。限制样本量小和随访期短限制了氯胺酮对MDD的长期影响的结论。结论本初步研究通过阐明外周炎症与WM微结构之间的关系，为炎症在MDD中的作用提供了证据。此外，我们证明了自由水扩散加权成像可能是一个有价值的工具，以确定哪些MDD患者受益于氯胺酮治疗的抗炎中介效应。
BackgroundAlterations in the peripheral inflammatory profile and white matter (WM) deterioration are frequent in Major Depressive Disorder (MDD). The present study applies free-water imaging to investigate the relationship between altered peripheral inflammation and WM microstructure and their predictive value in determining response to ketamine treatment in MDD.MethodsTen individuals with MDD underwent diffusion-weighted magnetic resonance imaging and a blood-draw before and 24 h after ketamine infusion. We utilized MANCOVAs and ANCOVAs to compare tissue-specific fractional anisotropy (FAT) and free-water (FW) of the forceps and cingulum, and the ratio of pro-inflammatory interleukin(IL)-8/anti-inflammatory IL-10 between individuals with MDD and 15 healthy controls at baseline. Next, we compared all baseline measures between ketamine responders (6) and non-responders (4) and analyzed changes in imaging and blood data after ketamine infusion.ResultsThe MDD group exhibited an increased IL-8/IL-10 ratio compared to controls at baseline (p= .040), which positively correlated with average FW across regions of interest (p= .013). Ketamine responders demonstrated higher baseline FATin the left cingulum than non-responders (p= .023). Ketamine infusion did not influence WM microstructure but decreased the IL-8/IL-10 ratio (p= .043).LimitationsThe small sample size and short follow-up period limit the conclusion regarding the longer-term effects of ketamine in MDD.ConclusionsThis pilot study provides evidence for the role of inflammation in MDD by illustrating an association between peripheral inflammation and WM microstructure. Additionally, we demonstrate that free-water diffusion-weighted imaging might be a valuable tool to determine which individuals with MDD benefit from the anti-inflammatory mediated effects of ketamine treatment.