Objective:To investigate the effect of early intervention with electroacupuncture (EA) on the gut microbiota in a mouse model of post-traumatic stress disorder(PTSD).Methods:Totally 32 C57BL/6 mice were randomly assigned to the following 4 groups ( n=8 for each group): Control group, EA group, PTSD group and PTSD+ EA group.After 7 days acclimation, mice in the PTSD group and PTSD+ EA group were subjected to modified single prolonged stress (mSPS). Mice in the EA group and PTSD+ EA group received EA (2/15 Hz, 1 mA, dilatational wave, 30 min/d) on "Baihui" for 7 days. Mice in the Control group and PTSD group received false stimulation (stimulated the same acupiont without electricity) for 7 days. Seven days after the last stimulation, elevated plus maze test and fear conditioning test were conducted to observe the effect of EA on PTSD-like behavior of mice. At the same time, feces of the mice were collected for gut microbiota detection by 16S rRNA sequencing.SPSS 19.0 was used for statistical analysis.One-way ANOVA was used for multiple group comparison and Bonferrani test was done for further pairwise comparision. Results:(1) There were statistically differences in the open arm activity time of the elevated plus maze test and the immobility time in contextual and cued fear conditioning test among the four groups ( F=6.93, 5.26, 14.51, all P<0.01). In the elevated plus maze test, mice in PTSD group ((60.17±15.52) s) showed significant less time in the open arms than mice in Control group((96.37±14.62) s) and PTSD+ EA group ((86.89±15.02) s) (both P<0.05). In the fear conditioning test, mice in PTSD group ((121.99±29.67) s, (130.82±29.11) s) showed significant increased immobility time both in contextual and cued fear conditioning tests than mice in Control group((74.50±26.65) s, (39.50±23.52) s) and PTSD+ EA group ((76.77±22.60) s, (102.17±3.39) s)(both P<0.05). (2) There were no significant differences among the four groups in the alpha diversity of gut microbiota ( F=0.79-2.45, all P>0.05). (3)Correlation analysis showed that 13 gut microbiotas were negatively correlated with the immobility time in contextual fear conditioning test, 2 gut microbiotas were positively correlated with it; 7 gut microbiotas were negatively correlated with the immobility time in cued fear conditioning test, 1 gut microbiota was positively correlated with it; 3 gut microbiotas were positively correlated with time spent in open arms of elevated plus maze test. Conclusion:Early intervention with EA can improve anxiety-fear like behaviors and gut microflora disorder in PTSD model mice.
目的 探讨电针(EA)干预对创伤后应激障碍(PTSD)小鼠前额叶皮质(PFC)磷脂酰肌醇(PI)和溶血磷脂酰肌醇(LPI)的影响.方法 将24只雄性C57BL/6小鼠随机分为对照组、模型组(PTSD)和电针治疗组(EA+PTSD).经适应性饲养后,模型组和电针治疗组均接受单次延长应激造模,造模后在小鼠百会穴分别给予电针刺激或假电针刺激.在最后一次电针干预结束后7 d进行行为学检测,之后处死小鼠,取PFC进行脂质组学分析,比较各处理组PI和LPI含量的差异,并分析差异脂质分子与行为学的相关关系.结果 模型组开臂停留时间低于对照组和电针治疗组,模型组环境诱发僵直时间和声音诱发僵直时间高于对照组和电针治疗组(P<0.05).模型组LPI(18:1)、LPI(18:0)以及LPI总含量均低于对照组和电针治疗组(P<0.05);模型组PI(17:0/20:4)、PI(18:2/20:4)和PI(18:1/22:6)的含量均低于对照组(P<0.05),电针治疗组PI(17:0/20:4)、PI(16:0/20:4)和PI(18:1/20:4)的含量均低于对照组(P<0.05).LPI(18:1)含量与开臂停留时间呈正相关(P<0.01),与环境诱发僵直时间呈负相关(P<0.05);LPI(18:0)含量和LPI总含量均与开臂停留时间呈正相关(P<0.05).结论 PTSD模型小鼠前额叶皮质LPI水平降低,电针在缓解PTSD样行为的同时,也上调了其前额叶皮质的LPI水平.
目的 研究精神分裂症(SP)患者记忆功能与症状的相关性.方法 选取SP患者120例,按照疾病类型的差异分成首发组64例与慢性组56例.通过韦氏记忆力测试(WMS)的短时和瞬时记忆量表评估两组患者的短时和瞬时记忆状况,以阳性和阴性综合征量表(PANSS)判定两组患者的精神症状严重性情况.并做相关性分析.结果 首发组WMS短时记忆中图片回忆、视觉再认、联想学习及瞬时记忆中倒背数字评分均低于慢性组(P<0.05).首发组PANSS阳性症状评分高于慢性组(P<0.05),阴性症状评分低于慢性组(P<0.05).相关性分析结果显示,SP患者WMS短时记忆中图片回忆、视觉再认、联想学习及瞬时记忆中倒背数字评分与PANSS阳性症状评分呈负相关(P<0.05),与PANSS阴性症状评分呈正相关(P<0.05).结论 SP患者可能存在不同程度的认知功能损害,且随着精神症状的不断加重,认知功能损害程度越高.
[目的]观察银杏酮酯对抑郁症大鼠的作用,并探讨其对海马CA1区组织5-羟色胺受体(5-hydroxytryptamine receptor,5-HT1AR)/环腺苷酸(cyclic adenosine mono-phosphate,cAMP)/蛋白激酶A(protein kinase A,PKA)通路的调控作用.[方法]取50只SD大鼠随机分为A组、B组、C组、P组和M组,各10只;另取10只正常SD大鼠记为N组.A、B、C、P和M组建模,同时A、B和C组分别给予35、70、140 mg/kg银杏酮酯灌服,P组给予10 mg/kg氟西汀灌服,N组和M组均给予等体积蒸馏水灌服,各组均1次/d,持续3周.对比各组体质量变化;糖水偏爱实验和强迫游泳实验评价干预前后抑郁样行为学改变;ELISA检测干预前后血清5-羟色胺(5-hydroxytryptamine,5-HT)含量,竞争法检测干预后大脑皮质组织5-HT含量;qRT-PCR检测海马CA1区组织5-HT1AR、cAMP反应元件结合蛋白(cAMP responsive element binding,CREB)、PKA mRNA表达;免疫组化法检测海马CA1区组织5-HT1AR、CREB、PKA蛋白表达并对比其光密度值(D),125碘(125I)标记放免法检测海马CA1区组织cAMP的含量.[结果]体质量、糖水偏爱实验、血清5-HT干预前后差值对比,M组均高于N组(P<0.05),P组和银杏酮酯3剂量组均低于M组(P<0.05),P组、B组和C组均低于A组(P<0.05),C组均低于P组、B组(P<0.05);强迫游泳不动时间干预前后差值对比,M组远长于N组(P<0.05),P组和银杏酮酯3剂量组均短于M组(P<0.05),P组、B组和C组均短于A组(P<0.05),C组短于P组、B组(P<0.05);干预后大脑皮质5-HT含量对比,M组低于N组(P<0.05),P组和银杏酮酯3剂量组均高于M组(P<0.05),P组、B组和C组均高于A组(P<0.05),C组高于P组、B组(P<0.05);各组海马CA1区组织5-HT1AR、CREB、PKA mRNA及蛋白表达、cAMP含量对比,M组上述指标均显著低于N组(P<0.05),A、B、C组和P组均显著高于M组(P<0.05),且银杏酮酯的作用均呈剂量依赖性.[结论]银杏酮酯可控制抑郁症大鼠的体质量下降,减轻抑郁样行为,改善血清和大脑皮质5-HT含量,推测该药物与氟西汀均可能通过调整5-HT1AR/cAMP/PKA通路,上调海马CA1区组织5-HT1AR、CREB、PKA mRNA及蛋白表达、增加cAMP含量实现抗抑郁作用,且银杏酮酯的抗抑郁作用呈剂量依赖性.
Objective To investigate the effects of repetitive transcranial magnetic stimulation (rTMS) combined with risperidone to improve white matter integrity on left hippocampus in patients with first-episode schizophrenia.Methods A total of 28 patients with schizophrenia were randomly divided into study group with rTMS combined with risperidone and control group with sham-rTMS combined with risperidone for 6 weeks of treatment.They were assessed with Positive and Negative Syndrome Scale (PANSS) and examined with diffusion tensor imaging(DTI) before and after treatment.Results The total score and all factor scores of PANSS in both groups after treatment were all significantly lower than those before treatment(P < 0.05).In study group,the FA value of white matter on left hippocampus after treatment was significantly higher than that before treatment(P <0.05)and the positive factor score of PANSS was significantly lower than that in control group(P < 0.05).In study group,the increased FA value was positively correlated with the decreased positive factor score of PANSS (P < 0.05).Conclusion It's effective for rTMS combined with risperidone to improve the clinical symptoms and white matter integrity on left hippocampus in patients with first-episode schizophrenia and there exists some correlation between them.
Objective To compare the antidepressive effect and cognitive imfluence of modified electroconvulsive therapy(MECT) and repetitive transcranial magnetic stimulation(rTMS) on medica-tion-resistant depression patients.Methods Totals of 40 patients with treatment-refractory and non-psy-chotic major depression were randomly divided into MECT group and rTMS group. They received two weeks of treatments with either MECT or rTMS and were assessed for efficacy and cognitive impairments before and after 1 and 2 weeks treatment by Hamilton Rating Scale for Depression(HAMD) and Clinical Memory Scale. Treat-ment Emergent Symptom Scale(TESS) was used to evaluate the side-effects. Moreover, medical examination, electrocardiogram and electroencephalogram examination were performed before and after treatment for safety. Results There was no difference between two groups before and at the end of week 1 and 2 on the total HAMD score(P=0.610,P=0.235) and cognitive impairment factors(P=0.639,P=0.793). However, Clinical Memo-ry Scale score and all factors of rTMS group was improved markedly at the end of week 2(P<0.05). Directed memory score, free recall deficit of picture score, image free recall score and portrait character recall score of MECT group was declined at the end of week 2(P<0.05). And the total score, directed memory score and por-trait character recall score of MECT group was lower than that of rTMS group(P<0.05). There was no significant difference between the two groups on the incidence of nausea, vomiting, headache(P>0.05), and more patients complained of memory decline in the MECT group(P<0.05).Conclusions rTMS and MECT have similar effi-cacy in treating treatment-refractory non-psychotic major depression. But rTMS is benefit to the improvement of cognitive performance with more safety than MECT.
Purpose To investigate auditory verbal hallucination (AVH)-specific patterns of brain activity within the resting-state networks (RSNs) that have been proposed to underpin the neural mechanisms of schizophrenia (SZ). Materials and Methods This cross-sectional study was approved by the local ethics committee, and written informed consent was obtained from all participants prospectively recruited. Independent component analysis was used to investigate RSNs in 17 patients with first-episode untreated SZ with AVHs, 15 patients with SZ without AVHs, and 19 healthy control subjects who underwent resting-state functional magnetic resonance imaging. Dual regression was implemented to perform between-group analysis. Regional brain function was then explored within RSNs by using the amplitude of low-frequency fluctuation. Two-sample t tests were used to compare regional brain function between the two patient groups, and Pearson correlation analysis was used to characterize the relationship between imaging findings and severity of AVHs. Receiver operating characteristic analysis was used to evaluate the diagnostic performance of these brain function measures. Results Independent component analysis demonstrated symptom-specific abnormal disrupted coactivation within the auditory, default mode, executive, motor, and frontoparietal networks and was pronounced in the auditory cortex, supramarginal gyrus, insula, putamen, dorsolateral prefrontal cortex, angular gyrus, precuneus, and thalamus (P < .05 with false discovery rate correction). Amplitude of low-frequency fluctuation analysis demonstrated similar patterns within these RSNs (P < .05 with false discovery rate correction). Furthermore, a positive correlation between the degree of coactivation within the motor network and the severity of AVHs was observed in patients with SZ with AVHs (r = 0.67, P = .003). The area under the receiver operating characteristic curve was 0.76-0.90 for all RSNs. Conclusion These findings indicate that dysfunctional brain regions are involved in auditory processing, language production and monitoring, and sensory information filtering in patients with SZ with AVHs, which may be helpful in furthering the understanding of pathophysiological correlates of AVHs in SZ. Online supplemental material is available for this article.
目的 探讨利培酮联合重复经颅磁刺激(rTMS)治疗首发精神分裂症的临床疗效,并观察其安全性及不良反应.方法 将60例首发精神分裂症患者随机分成研究组和对照组,研究组在利培酮基础上联合rTMS真刺激,对照组在利培酮基础上联合rTMS假刺激干预.分别于治疗前、治疗1周、2周及4周应用阳性和阴性症状量表(PANSS)评定临床疗效,采用不良反应量表(TESS)、生命体征、体格检查、临床实验室检查、心电图、脑电图评价安全性.结果 研究组和对照组PANSS总分及各因子分在治疗1周、2周及4周均显著下降(P<0.01);研究组的有效率在治疗2周时即高于对照组,差异具有统计学意义(P<0.01),而两组有效率在4周时差异无统计学意义(P=0.127);研究组阳性症状因子评分在治疗2周时即显著低于对照组(P<0.05),在4周末时差异有统计学显著性(P<0.01).研究组和对照组在治疗中均无严重不良反应发生,两组不良反应差异无统计学意义.结论 重复经颅磁刺激具有很好的安全性,联合利培酮使用可以提高治疗首发精神分裂症的疗效,尤其有助于改善阳性症状.