舍曲林联合重复经颅磁刺激治疗难治性抑郁症对照研究

目的 探讨抗抑郁剂联合重复经颅磁刺激治疗难治性抑郁症的临床疗效及安全性.方法将88例难治性抑郁症患者随机分为实验组45例,对照组43例,两组均口服舍曲林100 mg·d.治疗,实验组联合重复经颅磁刺激治疗,对照组联合无抽搐电休克治疗,观察4周.于治疗前及治疗4周末采用汉密顿抑郁量表评定临床疗效,并记录起效时间、脱落率、...     

氟西汀联合喹硫平治疗难治性抑郁症对照研究

目的 探讨氟西汀联合喹硫平治疗难治性抑郁症的l临床疗效与安全性.方法将58例难治性抑郁症患者随机分为研究组30例,对照组28例,两组均口服氟西汀治疗,研究组联合喹硫平治疗,对照组联合利培酮治疗,观察8周.于治疗前及治疗第2周、4周、6周,8周末采用汉密顿抑郁量表、临床总体印象量表评定临床疗效,副反应量表评定不良反应.结...     

舍曲林联合喹硫平治疗难治性抑郁症对照研究

目的 探讨舍曲林联合喹硫平治疗难治性抑郁症的临床疗效和安全性.方法 将58例难治性抑郁症患者随机分为两组,每组29例.两组均口服舍曲林治疗,在此基础上研究组联合喹硫平治疗,观察12周.于治疗前及治疗1周、2周、4周、6周、12周末采用汉密顿抑郁量表及汉密顿焦虑量表评定临床疗效,副反应量表评定不良反应.结果 治疗后两组汉密顿抑郁量表及汉密顿焦虑量表评分均较治疗前有显著性下降(P＜0.01),同期研究组均较对照组下降显著(P＜0.05或0.01);治疗12周末,研究组有效率65.5%,对照组为37.9%,研究组显著高于对照组(χ2=4.419,P＜0.05).研究组不良反应发生率为41.4%,对照组为34.5%,两组不良反应程度均较轻,同期副反应量表评分差异无显著性(P＞0.05).结论喹硫平对治疗难治性抑郁症具有增效作用;舍曲林联合喹硫平治疗难治性抑郁症疗效显著,起效快,安全性高,依从性好,显著优于单用舍曲林治疗.     

度洛西汀联合阿立哌唑治疗难治性抑郁症对照研究

目的：探讨度洛西汀联合阿立哌唑治疗难治性抑郁症的临床疗效和安全性。方法将93例难治性抑郁症患者随机分为两组,研究组口服度洛西汀联合阿立哌唑治疗,对照组单用度洛西汀治疗,观察8周。采用汉密顿抑郁量表评定临床疗效,副反应量表评定不良反应。结果治疗8周末研究组显效率59．1％、有效率77．3％,对照组分别为31．1％、42．2％,研究组显效率、有效率均显著高于对照组（χ^2＝7．04、11．35,P＜0．01）。两组不良反应较轻微,发生率比较差异无显著性（P＞0．05）。结论度洛西汀联合阿立哌唑治疗难治性抑郁症起效快,疗效显著,安全性高,显著优于单用度洛西汀治疗。     

Serotonin transporter gene polymorphisms and treatment-resistant depression

Major Depression Disorder (MDD) is a serious mental illness that is one of the most disabling diseases worldwide. In addition, approximately 15% of depression patients are defined treatment-resistant (TRD). Preclinical and genetic studies show that serotonin modulation dysfunction exists in patients with TRD. Some polymorphisms in the promoter region of the serotonin transporter gene (SLC6A4) are likely to be involved in the pathogenesis/treatment of MDD; however, no data are available concerning TRD.     

Pregnancy-associated glycoprotein (PAG) family localized in chorionic cells within the epitheliochorial/diffuse placenta of the alpaca (Lama pacos)

Pregnancy-associated glycoproteins (PAGs) are abundant embryo-originated products expressed in the pre-placental trophoblast and later in the post-implantational chorionic epithelium of some ungulate species. This paper describes the cellular immunolocalization of the chorionic PAG family in the epitheliochorial placenta type of the alpaca (Lama pacos—Lp), in which the PAGs were named ‘LpPAGs’. Placental Lp sections (5 μm) of different females near mid-pregnancy (150 days post coitum; dpc), advanced pregnancy (244-263 dpc) and late pregnancy (347 dpc) were used for cross-species (heterologous—ht) double fluorescent immunohistochemistry (htdF-IHC). The htdF-IHC was performed with primary rabbit polyvalent anti-porcine PAG polyclonals. The LpPAG immuno-complexes were visualized with secondary goat anti-rabbit immunoglobulins-conjugated with Alexa 488 fluorophore (green), among all nuclei of placental cells stained with propidium iodide (red). This is the first study reporting the immunolocalization of the LpPAG family identified by htdF-IHC at the feto/maternal interface during different pregnancy stages of the alpaca. The most dominant and strongest immune-positive LpPAG signals were found in the well-developed chorionic cell layer. Our htdF-IHC indicated relatively high epitope resemblance to that of the PAGs in camelids and pigs. These data increase our general knowledge of chorionic PAG localization during pregnancy-stage dependent development of the epitheliochorial diffuse placenta type in the alpaca.     

Can we increase the speed and efficacy of antidepressant treatments? Part II. Glutamatergic and RNA interference strategies

In the second part we focus on two treatment strategies that may overcome the main limitations of current antidepressant drugs. First, we review the experimental and clinical evidence supporting the use of glutamatergic drugs as fast-acting antidepressants. Secondly, we review the involvement of microRNAs (miRNAs) in the pathophysiology of major depressive disorder (MDD) and the use of small RNAs (e.g.., small interfering RNAs or siRNAs) to knockdown genes in monoaminergic and non-monoaminergic neurons and induce antidepressant-like responses in experimental animals.The development of glutamatergic agents is a promising venue for antidepressant drug development, given the antidepressant properties of the non-competitive NMDA receptor antagonist ketamine. Its unique properties appear to result from the activation of AMPA receptors by a metabolite [(2 S,6 S;2 R,6 R)-hydroxynorketamine (HNK)] and mTOR signaling. These effects increase synaptogenesis in prefrontal cortical pyramidal neurons and enhance serotonergic neurotransmission via descending inputs to the raphe nuclei. This view is supported by the cancellation of ketamine's antidepressant-like effects by inhibition of serotonin synthesis.We also review existing evidence supporting the involvement of miRNAs in MDD and the preclinical use of RNA interference (RNAi) strategies to target genes involved in antidepressant response. Many miRNAs have been associated to MDD, some of which e.g., miR-135 targets genes involved in antidepressant actions. Likewise, SSRI-conjugated siRNA evokes faster and/or more effective antidepressant-like responses. Intranasal application of sertraline-conjugated siRNAs directed to 5-HT_1A receptors and SERT evoked much faster changes of pre- and postsynaptic antidepressant markers than those produced by fluoxetine.     

合用新型抗精神病药治疗难治性抑郁症的疗效

难治性抑郁症用抗抑郁药合并新型抗精神病药治疗作为增效手段,是当前研究热点之一。新型抗精神病药利培酮、奥氮平、喹硫平、齐拉西酮、阿立哌唑分别与抗抑郁药西酞普兰、舍曲林、帕罗西汀、艾司西酞普兰及氟伏沙明合用治疗难治性抑郁症,均采用汉密尔顿抑郁量表(HAMD-17)评定治疗效果,治疗结束后两组HAMD评分均显著降低,以研究组疗效较好而快,显示抗抑郁药合用新型抗精神病药治疗难治性抑郁症优于单用抗抑郁药。其机制与新型抗精神病药对5-羟色胺受体的阻断作用或对多巴胺及去甲肾上腺素的影响有关。作者对近年来国内外有关合用新型抗精神病药治疗难治性抑郁症的部分报道综述如下。     

氯胺酮联合无抽搐电休克在治疗难治性抑郁症中对血清脑源性神经营养因子和认知功能的影响

目的 探讨以氯胺酮为麻醉剂,联合无抽搐电休克治疗(MECT)对难治性抑郁症病人血清脑源性神经营养因子和认知功能的影响.方法 将62例难治性抑郁症病人,按照入院时间顺序随机分成异丙酚组和氯胺酮组,每组31例.异丙酚组使用异丙酚为麻醉剂进行MECT治疗,氯胺酮组使用氯胺酮为麻醉剂进行MECT治疗.记录两组病人治疗前及治疗1~8次后的临床指标,制作并比较两组病人的汉密尔顿抑郁测量(HAMD),认知功能表包括威斯康星卡片分类(WCST)与汉诺塔(TOH)测验,以及血清脑源性神经营养因子(BDNF)浓度水平.结果 两组病人进行治疗2次后血清中BDNF无明显变化;在第4次治疗后氯胺酮组BDNF的水平较异丙酚组高(P<0.05);在第8次治疗后,两组病人BDNF水平均有升高,其中氯胺酮组显著高于异丙酚组(P<0.05);氯胺酮组病人WCST评分完成分类数高于异丙酚组,异丙酚组病人总错误数高于氯胺酮组(P<0.05);TOH评分两组各项分类数据均差异无统计学意义(P>0.05);进行治疗后两组病人HAMD评分值均有降低,氯胺酮组病人HAMD分值均低于异丙酚组(P<0.05).结论 在MECT中使用氯胺酮为麻醉剂治疗难治性抑郁症病人可提高病人血清中BDNF浓度水平,快速降低病人HAMD评分,能有效提高病人认知功能,适合临床推广.