抗精神病药早期疗效及对预后的预测研究

目的验证抗精神病药的早期疗效及对预后的预测。方法对2007年10月至2009年10月在深圳市康宁医院住院治疗的精神分裂症患者筛选入组,分别给予氯丙嗪、利培酮、奥氮平、喹硫平治疗,在入组基线和第1、2、3、4、6、8周末评定PANSS量表,计算分析各周PANSS总分和各因子得分及其减分率,计算分析前3周PAN-SS总分减分率对第4周PANSS总分减分的预测敏感度、特异度、预测值、似然比,分析不同界值的预测效率。结果共入组216例,有效数据为1～4用资料180例;PANSS总分及大多数因子在入组第1、2周出现明显减分;前4周PANSS总分呈现非匀速减分,其中第2周减分幅度最大（占4周总减分值的40％）;阳性量表等5个因子减分显著,而激活性、抑郁减分不显著;以第2周20％或第3周40％作为PANSS总分减分率分界值预测第4周PANSS总分减分率预测效率最高。结论抗精神病药治疗存在早期疗效;其疗效显现在时间上呈现非线性特征,其中第2周为主要显效时间段;抗精神病药的疗效特征在第2周即已显现并对后期疗效有一定预测。     

A preliminary analysis of association between the down-regulation of microRNA-181b expression and symptomatology improvement in schizophrenia patients before and after antipsychotic treatment

Despite the growing evidences on the relation of altered expression of miRNAs and schizophrenia, most schizophrenia subjects have an extensive antipsychotic treatment history and the pharmacological effects on miRNA expression are largely unknown. This study aimed to investigate the change of plasma microRNA-181b level and improvement of symptomatology before and after six-week antipsychotic treatment in schizophrenia patients, and explore their association. A total of 20 schizophrenia patients absent of antipsychotics and 20 age-and gender-matched normal controls were enrolled, and tested for 9 schizophrenia-associated microRNA (miR-30e, miR-34a, miR-181b, miR-195, miR-346, miR-432, miR-7, miR-132 and miR-212) expression levels in plasma using quantitative RT-PCR and for symptomatology improvement using Positive And Negative Syndrome Scale (PANSS) before and after treatment (olanzapine, quetiapine, ziprasidone and risperidone) for the patients only. Compared with the normal control group, the expression levels of miRNA-181b, miRNA-30e, miRNA-34a and miRNA-7 of the patients group were significantly higher (p < 0.05). Compared with those before treatment in the patient group, the symptomatology scores were significantly lower (p < 0.001), and the expression level of microRNA-181b was significantly down-regulated after treatment (p < 0.05). The change of miRNA-181b expression was positively correlated with the improvement of negative symptoms and lack of response symptoms (r = 0.502 and 0.557, P < 0.05, accounting for 20.2% and 26.4% respectively), and their therapeutic effects with OR being 11.283 and 5.119 respectively. We conclude that miRNA-181b, miRNA-30e, miRNA-34a and miRNA-7 are probably involved in pathogenesis of SZ, and the significant down-regulation of miRNA-181b expression predicts improvement of negative symptoms to treatment, and thus can serve as a potential plasmamolecular marker for antipsychotic responses.     

Associations of serum brain-derived neurotrophic factor with cognitive impairments and negative symptoms in schizophrenia

Brain-derived neurotrophic factor (BDNF) may be involved in the pathophysiology of schizophrenia. The aim of this study was to examine the associations of serum BDNF levels with the cognition and clinical characteristics in patients with schizophrenia. Sixty-three patients with schizophrenia and 52 age- and sex-matched healthy controls were examined with neuropsychological tests. Serum BDNF levels were determined by enzyme-linked immunosorbent assay (ELISA). There were no significant differences in serum BDNF levels between normal controls and patients with schizophrenia. Serum BDNF levels of normal controls showed negative correlations with verbal working memory, but this was not the case with schizophrenic patients. Meanwhile, serum BDNF levels of schizophrenic patients showed positive correlations with the scores of the Scale for the Assessment of Negative Symptoms (SANS) and the Information subtest scores of Wechsler Adult Intelligence Scale Revised (WAIS-R). Serum BDNF levels are related with the impairment of verbal working memory and negative symptoms in patients with schizophrenia.     

齐拉西酮与利培酮治疗精神分裂症对照研究

目的评价齐拉西酮治疗精神分裂症的临床疗效和安全性。方法将70例精神分裂症患者随机分为两组各35例,研究组口服齐拉西酮治疗,对照组口服利培酮治疗,观察8w。于治疗前及治疗第2w、4w、8w末采用阳性与阴性症状量表、副反应量表评定临床疗效和不良反应。结果治疗8w末,两组总有效率均为88．57％;治疗第2w末起,两组阳性与阴性症状量表总分均较治疗前有显著性下降（P均〈0．01）,并随着治疗的延续呈持续性下降;同期两组间比较均无显著性差异（P均〉0．05）。研究组主要不良反应表现为锥体外系反应、头痛、嗜睡、心电图异常等,未出现体重增加、血糖增高、泌乳素改变等;对照组不良反应主要表现为泌乳素改变、锥体外系反应、体重增加、失眠等。治疗后两组副反应量表评分均无显著性差异（P〉0．05）。结论齐拉西酮与利培酮治疗精神分裂症疗效均显著,不良反应轻微,但齐拉西酮不引起体重增加、血糖增高和泌乳素的改变,适合于肥胖、血糖、血脂异常或女性患者。     

齐拉西酮与氯氮平治疗精神分裂症对照研究

目的评价齐拉西酮治疗精神分裂症患者的临床疗效及安全性。方法将61例首发精神分裂症患者随机分为两组,研究组31例,口服齐拉西酮治疗,对照组30例,口服氯氮平治疗,观察8w。于治疗前及治疗第1w、2w、4w、8w末采用阳性与阴性症状量表评定临床疗效,副反应量表评定不良反应。结果治疗8w末,研究组显效率为82．6％,对照组为85．13％,两组比较无显著性差异（P〉0．05）。阳性与阴性症状量表评分,两组治疗后总分及各因子分均较治疗前有极显著性下降（P均〈0．01）,并随着治疗的延续呈持续性下降;两组间同期评分比较均无显著性差异（P均〉0．05）。两组不良反应均较轻微,但研究组体重增加发生率显著低于对照组（P〈0．05）。结论齐拉西酮治疗首发精神分裂症疗效显著,总体疗效与氯氮平相当,但不良反应轻微,安全性更高,服药依从更好。