摘要
目的分析甲基苯丙胺(MA)依赖患者重复经颅磁刺激(rTMS)治疗前后的代谢物差异性,研究MA依赖潜在标志物及rTMS治疗后相关代谢产物变化规律。方法选取30例MA依赖患者(研究组)和30名健康人(对照组),予以4周rTMS治疗。采用强迫性毒品使用量表(OCDUS)评定疗效,采用超高效液相色谱-高分辨质谱联用(UPLC-MS)技术分析治疗前后血浆代谢产物变化,采用主成分分析(PCA)、正交偏最小二乘法判别分析(OPLS-DA)进行多维统计分析,筛选差异代谢物。结果研究组rTMS治疗后OCDUS总分及毒品的影响、渴求的频率及毒品失控评分均较治疗前降低(P<0.01)。与对照组相比,研究组基线时血浆中有34个差异代谢物,涉及D-谷氨酰胺和D-谷氨酸代谢,亚油酸代谢,丙氨酸、天冬氨酸和谷氨酸代谢等12条代谢通路;研究组经rTMS治疗后血浆中检测36个差异代谢物,涉及氨基酰基-tRNA生物合成,缬氨酸、亮氨酸和异亮氨酸生物合成,精氨酸和脯氨酸代谢等12条代谢通路。结论MA依赖患者中存在多条代谢通路的失调,rTMS治疗可能通过影响氨基酸代谢改善症状,研究发现的差异代谢物可作为MA依赖的潜在生物标志物。
Objective To explore the difference of metabolites in patients with methamphetamine(MA)dependence before and after repetitive Transcranial Magnetic Stimulation(rTMS),and to find the potential markers of MA dependence as well as the change rules of related metabolites after rTMS treatment.Methods A total of 30 patients with MA dependence in study group and 30 healthy controls in control group were selected and treated with rTMS for 4 weeks.They were assessed with Obsessive Compulsive Drug Use Scale(OCDUS).Plasma metabolites were analyzed by ultra-high performance liquid chromatography-high resolution mass spectrometry(UPLC-MS)before and after treatment.Multi-dimensional statistical analysis was performed by principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA)to screen differential metabolites.Results After rTMS treatment,the total score and factor scores of the influence of drug,the frequency of craving and drug out of control of OCDUS in study group decreased significantly compared with those before treatment(P<0.01).Compared with control group,34 differential metabolites were detected in study group at baseline,involving 12 metabolic pathways including d-glutamine and d-glutamate metabolism,linoleic acid metabolism,alanine,aspartic acid,glutamate metabolism and etc.;36 differential metabolites were detected in study group after rTMS treatment,involving 12 metabolic pathways including aminoacyl-tRNA biosynthesis,valine,leucine and isoleucine biosynthesis,arginine and proline metabolism and etc.Conclusion There are metabolic disorders in multiple metabolic pathways in MA-dependent patients,and rTMS treatment may improve symptoms by affecting amino acid metabolism.Differential metabolites can be used as potential biomarkers for MA dependence.
作者
周亚男
杨栋
罗银利
杨超
ZHOU Yanan;YANG Dong;LUO Yinli(Brain Hospital of Hunan Province,Changsha 410007,China)
出处
《精神医学杂志》
2020年第6期405-411,共7页
Journal of Psychiatry
基金
湖南省临床医疗技术创新引导计划项目(编号:2017SK50315)
湖南省卫计委项目(编号:B20180484)
湖南省中医药管理局项目(编号:201845)
湖南省自然科学基金项目(编号:2018JJ2221)。
关键词
超高效液相色谱-高分辨质谱
代谢组学
差异代谢物
甲基苯丙胺依赖
Ultra-high performance liquid chromatography-high resolution mass spectrometry
Metabolomics
Differential metabolites
Methamphetamine dependence