动脉瘤性蛛网膜下腔出血后体液miRNA-706与精神障碍发生的相关性研究

A Study on the Correlation between miRNA-706 and Mental Disorder after Aneurysmal Subarachnoid Hemorrhage

摘要: 目的：探讨动脉瘤性蛛网膜下腔出血(aSAH)患者脑脊液和血清中miRNA706 (miR-706)与精神障碍发生的相关性。方法：选择2021至2023年间入住包头市中心医院神经内科符合入组标准的aSAH患者为实验组，采集入院后3 d内的血清和脑脊液，选择同期与aSAH患者年龄、性别相匹配的周围血管病患者为对照组，采用PCR法评估两组样本中血清和脑脊液miR-706的表达水平；针对aSAH组，我们收集了基础信息，包括入院时Hunt-Hess分级、Fisher分级、WFNS分级、MRS评分等，使用HAMA、HAMD量表评估aSAH患者发病6个月时的焦虑、抑郁精神障碍，以探究其精神障碍问题是否与体液中miR-706水平以及其他因素存在关联。结果：研究共纳入40名患者，获取了80份样本，同时获得80份对照组样本。(1) 结果显示，实验组的血清miR-706、脑脊液miR-706均小于对照组且有显著差异(P < 0.05)。(2) 通过HAMA及HAMD量表评分结果将aSAH患者分为精神障碍组与精神状态正常组，通过对两组基线变量及院内变量的比较、多因素Logistic回归分析及绘制ROC曲线得出以下结果：① 发病6个月时有焦虑组23例，无焦虑正常组17例，有焦虑组血清和脑脊液miR-706水平较无焦虑正常组明显下降，具有统计学差异(P < 0.05)；血清miR-706 AUC = 0.784、截断值为0.11、敏感度88.20%、特异度56.50%；脑脊液miR-706 AUC = 0.806、截断值为5.10、敏感度76.50%、特异度82.60%。其中联合指标的预测和诊断的价值最大(AUC = 0.898、截断值为0.25、敏感度100.00%、特异度73.90%)。② 发病6个月时有抑郁组12例，无抑郁正常组28例，有抑郁组血清和脑脊液miR-706水平较无抑郁正常组降低，具有统计学差异(P < 0.05)；血清miR-706 AUC = 0.775、截断值为0.81、敏感度46.40%、特异度100.00%；脑脊液miR-706 AUC = 0.807、截断值为4.68、敏感度78.60%、特异度100.00%。其中联合指标的预测和诊断的价值最大(AUC = 0.896、截断值为0.73、敏感度78.60%、特异度100.00%)。结论：① aSAH患者早期血液和脑脊液中miR-706水平均显著低于对照组，具有一定的特异性。② aSAH患者早期血清和脑脊液miR-706水平降低，与发病6个月时焦虑、抑郁的发生具有相关性，将血清和脑脊液联合诊断，具有更高的特异性和敏感性。③ miR-706可作为aSAH后焦虑、抑郁的精神并发症的新型生物标志物。④ 血清和脑脊液miR-706水平降低是aSAH患者发生焦虑、抑郁的危险因素。

Abstract: Objective: To investigate the association between miRNA706 (miR-706) levels in cerebrospinal fluid and serum and the occurrence of psychiatric disorders in patients with aneurysmal Subarachnoid Haemorrhage (aSAH). Methods: Patients with aSAH admitted to the Department of Neurology at Baotou Central Hospital between 2021 and 2023 who met the inclusion criteria were selected as the experimental group. Serum and cerebrospinal fluid samples were collected within 3 days of admission. Patients with peripheral vascular disease matched for age and sex with the aSAH patients during the same period were selected as the control group. The expression levels of miR-706 in serum and cerebrospinal fluid samples from both groups were assessed using PCR. For the aSAH group, we collected baseline information, including Hunt-Hess classification, Fisher classification, WFNS classification and MRS scores at admission. We used the HAMA and HAMD scales to assess anxiety and depression in aSAH patients six months after onset, to investigate whether their mental health issues were associated with miR-706 levels in body fluids and other factors. Results: The study included 40 patients, yielding 80 samples, alongside 80 control samples. (1) Results showed that serum miR-706 and cerebrospinal fluid miR-706 levels in the experimental group were lower than those in the control group, with significant differences (P < 0.05). (2) Using scores from the HAMA and HAMD scales, aSAH patients were classified into a group with psychiatric disorders and a group with normal mental status. Comparison of baseline and in-hospital variables between the two groups, multivariate logistic regression analysis, and ROC curve analysis yielded the following results: (1) At 6 months post-onset, there were 23 cases in the anxiety group and 17 in the normal group without anxiety. The serum and cerebrospinal fluid miR-706 levels in the anxiety group were significantly lower than those in the normal group without anxiety, with a statistically significant difference (P < 0.05); serum miR-706: AUC = 0.784, cut-off value = 0.11, sensitivity = 88.20%, specificity = 56.50%; cerebrospinal fluid miR-706: AUC = 0.806, cut-off value = 5.10, sensitivity = 76.50%, specificity = 82.60%. Among these, the combined markers demonstrated the greatest predictive and diagnostic value (AUC = 0.898, cut-off value 0.25, sensitivity 100.00%, specificity 73.90%). (2) At 6 months post-onset, there were 12 cases in the depressed group and 28 cases in the non-depressed control group. Serum and cerebrospinal fluid miR-706 levels in the depressed group were lower than those in the non-depressed control group, with a statistically significant difference (P < 0.05); Serum miR-706: AUC = 0.775, cut-off value = 0.81, sensitivity 46.40%, specificity 100.00%; cerebrospinal fluid miR-706: AUC = 0.807, cut-off value = 4.68, sensitivity 78.60%, specificity 100.00%. Among these, the combined markers demonstrated the highest predictive and diagnostic value (AUC = 0.896, cut-off value 0.73, sensitivity 78.60%, specificity 100.00%). Conclusions: (1) In the early stages of aSAH, miR-706 levels in both blood and cerebrospinal fluid were significantly lower than in the control group, demonstrating a certain degree of specificity. (2) Reduced levels of miR-706 in serum and cerebrospinal fluid in the early stages of aSAH were associated with the occurrence of anxiety and depression at 6 months post-onset; combined diagnosis using serum and cerebrospinal fluid exhibited higher specificity and sensitivity. (3) miR-706 may serve as a novel biomarker for psychiatric complications such as anxiety and depression following aSAH. (4) Reduced levels of miR-706 in serum and cerebrospinal fluid are risk factors for the development of anxiety and depression in aSAH patients.