Evidence in primates supporting the use of chemogenetics for the treatment of human refractory neuropsychiatric disorders

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阿立哌唑与氯氮平对精神分裂症患者生活质量的影响

目的研究阿立哌唑与氯氮平对精神分裂症患者生活质量的影响。方法将80例精神分裂症患者随机分为两组各40例,研究组口服阿立哌唑治疗,对照组口服氯氮平治疗,疗程12w。于治疗前及治疗第12w末采用潘氏量表评定临床疗效,生活质量综合评定问卷评定生活质量,副反应量表评定不良反应。结果治疗12w末两组总有效率相当,但研究组显效率显著高于对照组(P<0.05)。潘氏量表评分两组治疗12w末总分及各因子分均较治疗前有极显著性下降(P<0.01);研究组总分及阴性症状因子分较对照组下降显著(P<0.05或0.01)。生活质量综合评定问卷评分研究组除物质生活维度无显著变化外,其它各维度分均较治疗前有显著性提高(P<0.05),躯体健康、心理健康、社会功能维度分均显著高于对照组(P<0.05)。研究组不良反应发生率较对照组低,且程度较轻。结论阿立哌唑治疗精神分裂症疗效显著,改善患者的阴性症状及生活质量明显优于氯氮平,安全性高,依从性好,有利于患者重返社会。     

磁石枕治疗顽固性幻听疗效与脑电地形图变化的关系

目的磁石枕治疗顽固性幻听疗效与脑电地形图变化的关系。方法磁石枕、氯氮平两组患者在入组前及治疗3个月后的脑电地形图检测对比。结果顽固性幻听患者在入组前脑电地形图θ、δ、β频域在各脑区功率值明显增高,而α频域则明显降低,经磁石枕3个月治疗后,各频域、各脑区的功率值趋于正常。氯氮平组治疗3个月后,θ、δ、β各频域、各脑区的功率值变化不明显,可是α频域的功率值则明显增高。结论磁石枕的疗效与脑电地形图的改善有密切关系,α频域的增高与氯氮平的副作用有关。     

电针联合氯氮平治疗难治性精神分裂症的疗效观察

目的研究电针联合氯氮平治疗难治性精神分裂症的疗效。方法选取2017年2月至2019年3月本院收治的60例难治性精神分裂症患者作为研究对象,根据单双数分组方式分为对照组和观察组,各30例。对照组采用氯氮平药物治疗,观察组采用电针联合氯氮平治疗,比较两组临床症状、临床疗效及不良反应发生率。结果治疗后2、4、8周,观察组PANSS评分均优于对照组,差异有统计学意义(P<0.05)。观察组治疗总有效率为90.00%,高于对照组的66.67%,差异有统计学意义(P<0.05)。观察组不良反应发生率为10.00%,低于对照组的33.33%,差异有统计学意义(P<0.05)。结论电针联合氯氮平治疗难治性精神分裂症临床疗效显著,能有效改善患者的病情症状,降低不良反应发生率,促使患者康复。     

丙戊酸钠与改良型无抽搐电休克治疗对氯氮平抵抗的难治性精神分裂症疗效和安全性比较

目的比较丙戊酸钠与改良型无抽搐电休克治疗（modified electroconvulsive therapy, MECT）对氯氮平抵抗的难治性精神分裂症（Clozapine-resistant schizophrenia, CRS）疗效和安全性的差异。方法本研究招募了90例CRS患者,进行为期8周随机对照试验,最终78例完成试验,脱落12例。将患者随机分为3组： (1) MECT联合氯氮平组(MC组)30例,完成28例、脱落2例;(2) 丙戊酸钠联合氯氮平组(VC组)30例,完成27例、脱落3例;（3） 维持原治疗组（对照组）30例,完成23例、脱落7例。采用阳性与阴性症状量表(The Positive and Negative Syndrome Scale, PANSS)评定临床疗效,采用血常规、血生化指标、体格检查及心电图评估安全性。结果在治疗4周和8周后MC组PANSS精神病理分和PANSS总分均较入组前显著下降（P<0.05）,而VC组和对照组均没有这种差异。PANSS阳性量表分和PANSS总分,干预与时间存在交互效应,简单效应分析发现只有PANSS总分存在组间差异。PANSS精神病理分存在组间差异（F=3.89,P=0.025）。同期组间对照比较发现治疗4周和8周的PANSS精神病理分以及治疗8周的PANSS总分减分幅度大于VC组和对照组（P<0.05）。3组间安全性比较差异无统计学意义(P均>0.05)。结论MECT联合治疗方案对CRS的疗效优于丙戊酸钠,且具有较好的安全性。     

睡眠宝胶囊中非法掺入化学药品的检测方法研究

目的 建立薄层色谱结合超高压液相色谱-质谱联用法快速筛查及鉴定睡眠宝胶囊中非法掺加的氯氮平、地西泮、艾司唑仑。方法 采用硅胶GF254板,乙酸乙酯-无水乙醇-氨水(50∶2∶0.5)为展开剂,在254 nm下检视。色谱条件为：Aglient ZORBAX SB C₁₈柱(100 mm×2.1 mm,1.8 μm),流动相20 mmol·L^-1醋酸铵溶液-甲醇(50∶50),流速0.3 mL·min^-1,检测波长225 nm,柱温35 ℃,正离子扫描检测。结果 睡眠宝胶囊非法掺入氯氮平、地西泮、艾司唑仑在254 nm下显明显的斑点,通过UPLC-PDA-Q TOF MS可进一步快速确证。结论 本方法操作简便,结果可靠,可用于快速筛查及确证睡眠宝胶囊中非法掺入氯氮平、地西泮及艾司唑仑。     

Cannabidiol Attenuates Sensorimotor Gating Disruption and Molecular Changes Induced by Chronic Antagonism of NMDA receptors in Mice

Background:

Preclinical and clinical data suggest that cannabidiol (CBD), a major non-psychotomimetic compound from Cannabis sativa, induces antipsychotic-like effects. However, the antipsychotic properties of repeated CBD treatment have been poorly investigated. Behavioral changes induced by repeated treatment with glutamate N-methyl-D-aspartate receptor (NMDAR) antagonists have been proposed as an animal model of schizophrenia-like signs. In the present study, we evaluated if repeated treatment with CBD would attenuate the behavioral and molecular modifications induced by chronic administration of one of these antagonists, MK-801.

Methods:

Male C57BL/6J mice received daily i.p. injections of MK-801 (0.1, 0.5, or 1mg/kg) for 14, 21, or 28 days. Twenty-four hours after the last injection, animals were submitted to the prepulse inhibition (PPI) test. After that, we investigated if repeated treatment with CBD (15, 30, and 60mg/kg) would attenuate the PPI impairment induced by chronic treatment with MK-801 (1mg/kg; 28 days). CBD treatment began on the 6th day after the start of MK-801 administration and continued until the end of the treatment. Immediately after the PPI, the mice brains were removed and processed to evaluate the molecular changes. We measured changes in FosB/ΔFosB and parvalbumin (PV) expression, a marker of neuronal activity and a calcium-binding protein expressed in a subclass of GABAergic interneurons, respectively. Changes in mRNA expression of the NMDAR GluN1 subunit gene (GRN1) were also evaluated. CBD effects were compared to those induced by the atypical antipsychotic clozapine.

Results:

MK-801 administration at the dose of 1mg/kg for 28 days impaired PPI responses. Chronic treatment with CBD (30 and 60mg/kg) attenuated PPI impairment. MK-801 treatment increased FosB/ΔFosB expression and decreased PV expression in the medial prefrontal cortex. A decreased mRNA level of GRN1 in the hippocampus was also observed. All the molecular changes were attenuated by CBD. CBD by itself did not induce any effect. Moreover, CBD effects were similar to those induced by repeated clozapine treatment.

Conclusions:

These results indicate that repeated treatment with CBD, similar to clozapine, reverses the psychotomimetic-like effects and attenuates molecular changes observed after chronic administration of an NMDAR antagonist. These data support the view that CBD may have antipsychotic properties.