精神分裂症患者转录因子4基因mRNA水平的分析对照研究

目的:探讨首发未用药的精神分裂症患者治疗前后转录因子4(TCF4)的基因表达水平及其与精神分裂症症状之间的相关性。方法:于2013年4月至10月期间入组首发未用药的精神分裂症患者28例(研究组),接受非典型抗精神病药治疗12周,同时入组正常对照者40名。采用实时定量聚合酶链反应(RT-qPCR)比较研究组与正常对照组、研究组治疗前后外周血中TCF4基因mRNA水平,并进一步分析患者治疗前后TCF4基因表达水平的差异与阳性与阴性症状量表(PANSS)评分之间的相关性。结果:与正常对照组相比,研究组TCF4的基因表达水平显著增高(P=0.000);与治疗前相比,研究组治疗12周后TCF4的基因表达水平显著降低(P=0.007)。研究组治疗前后TCF4基因表达水平差异与PANSS的各个子项目得分及总分之间的差异均无显著相关(P均0.05)。结论:精神分裂症患者存在TCF4基因的过度表达;抗精神病药治疗能够显著降低其TCF4基因的表达水平。     

精神分裂症患者血清非编码小分子RNA-320a及RNA-320b表达的研究

目的:探讨精神分裂症患者血清非编码小分子RNA(miR)-320a、320b的表达。方法:应用实时荧光定量逆转录聚合酶链式反应技术(RT-PCR)检测30例首次发病的精神分裂症患者(发病组)、30例治疗后临床缓解的精神分裂症者(缓解组)和30名正常对照者(健康对照组)血清miR-320a及miR-320b表达水平。结果:发病组和缓解组血清miR-320a和miR-320b表达明显低于健康对照组(P均0.001),且发病组明显低于临床治愈组(P均0.05)。结论:精神分裂症患者血清miR-320b和miR-320a表达低,并与病情有关。     

双相障碍患者血浆微小RNA(miR)-34a、miR-181b及miR-137水平及临床意义

目的:检测双相障碍(BD)患者血浆微小RNA (miR)-34a、miR-181b及miR-137水平,并分析其临床意义。方法:选取2016年3月至2018年3月BD患者106例为研究对象,其中躁狂发作58例,抑郁发作48例,选取同期健康体检者100例为对照组。利用实时定量聚合酶链反应(qRT-PCR)法检测外周血中miR-34a、miR-181b、miR-137表达水平;利用蒙哥马利抑郁评定量表(MADRS)和杨氏躁狂评定量表(YMRS)对BD患者进行评分。结果:BD抑郁发作组与躁狂发作组患者血浆miR-34a、miR-181b水平均显著高于对照组,miR-137水平显著低于对照组(P0.05);躁狂组血浆miR-34a水平显著高于抑郁组(P0.05)。BD患者血浆miR-34a、miR-181b水平与MADRS、YMRS评分显著正相关(P0.05);miR-137水平与MADRS、YMRS评分呈负相关(P0.05)。血浆miR-34a、miR-181b、miR-137水平三者联合诊断预测BD发生的曲线下面积(AUC)为0.875,对应敏感度为87.00%,特异性为91.80%。结论:BD患者血浆miR-34a、miR-181b、miR-137水平异常,三者联合检测对BD具有较高诊断价值。     

1986年至2006年间4个年份唐山市精神分裂症住院患者抗精神病药物使用变化趋势

目的 分析近20年精神分裂症住院患者抗精神病药物治疗种类和剂量变化趋势.方法 调查1986年、1996年、2001年和2006年4个年份在唐山市6所精神病院出院的2 718例精神分裂症患者的3 195份住院病历,用专门设计的调查表记录患者的社会人口学资料、疾病特征以及患者出院时药物治疗信息.结果 ①治疗药物的变化:1986年、1996年、2001年和2006年最常使用的抗精神病药物分别是第一代抗精神病药物、氯氮平、氯氮平、除氯氮平外的第二代抗精神病药物,使用率分别为93.8%(396/422)、45%(285/634)、59.9%(557/930)、51.6%(623/1206).2006年氯氮平使用率达35.7%(431/1206).4个年份间患者出院时合并使用2种以上抗精神病药物治疗的比例旱升高趋势(趋势X~2=99.10,P＜0.001),从1986年的10.43%(44/422)渐升至2006年的26.29%(317/1209).②药物剂量变化:4个年份出院时患者服用抗精神病药物的氯丙嗪等效日剂量组间比较差异有统计学意义(Kruskal-Wallis X~2=43.32,P＜0.001),4个年份的出院患者日服药剂量随年份增长而呈下降趋势(Spearman R=-0.13,P＜0.001);抗精神病药的单一治疗日剂量低于合并治疗,差异有统计学意义(Kruskal-Wallis X~2=14.23,P＜0.001).③多元回归分析表明,患者出院时服用抗精神病药物的氯丙嗪等效剂量与抗精神病药物联合治疗(b=163.86,P＜0.001)、住院大数(b:25.76,P＜0.001)呈正相关;与使用第二代抗精神病药物(b=-114.92,P＜0.001)、发病年龄(b=-3.87,P＜0.001)呈负相关.结论 近20年第二代抗精神病药物已逐渐成为抗精神病治疗的主要用药,抗精神病药合并治疗的比例增加.临床实践中应考虑到氯氮平一直保持较高使用率的利弊和合并用药可能带来的药物不良反应.     

抗精神病药治疗对外周血单核细胞miRNA-92a-3p表达的影响

目的:探讨抗精神病药治疗对外周血单核细胞miRNA-92a-3p表达的影响。方法:给予26例汉族精神分裂症患者(患者组)非典型抗精神病药(奥氮平、喹硫平、氯氮平、利培酮、齐拉西酮、阿立哌唑)单药治疗12周;治疗前后使用阳性和阴性症状量表(PANSS)评估临床症状;采用实时定量荧光PCR检测外周血单核细胞内miRNA-92a-3p相对表达水平,并与48名正常者(对照组)比较;分析治疗前后PANSS评分与miRNA-92a-3p的相对表达量变化的关系。结果:患者组治疗前后外周血单核细胞内miRNA-92a-3p相对表达量明显高于对照组(P均0.01),且治疗后显著高于治疗前(P0.05);患者组治疗前后miRNA-92a-3p相对表达量变化与PANSS总分变化无相关性。结论:精神分裂症患者外周血单核细胞miRNA-92a-3p相对表达量增高,抗精神病药治疗进一步提高其表达水平。     

精神分裂症首发患者新型抗精神病药治疗前后认知功能的变化

目的:探讨首次发病的精神分裂症患者短期非典型抗精神病药治疗后认知功能的变化。方法:45例首次发作的精神分裂症患者(患者组)给与非典型抗精神病药单药治疗8周;治疗前后给予简明精神病评定量表(BPRS)、公认认知成套测验(MCCB)进行临床及认知功能评估,结果与48名人口学资料相匹配的健康对照者(正常对照组)比较。结果:患者组29例完成8周治疗,治疗后BPRS评分较治疗前显著降低(t=6.87,P0.01);治疗前MCCB中信息处理速度、注意/警觉、工作记忆、词语学习、视觉学习、推理与问题解决的得分显著低于正常对照组(t=2.33~4.45,P均0.05);治疗8周后MCCB中注意/警觉得分和工作记忆得分较治疗前明显提高(t=2.80,t=2.16,P均0.05)。结论:短期非典型抗精神病药治疗精神分裂症首发患者临床症状有明显缓解,但认知功能无明显改善。     

不同性别和年龄的精神分裂症患者服用抗精神病药的等效剂量比较分析

目的:探讨不同性别和不同年龄的精神分裂症患者服用抗精神病药等效剂量的差异性。方法:对1 552例精神分裂症住院患者的用药情况进行回顾性调查分析,按照服用的抗精神病药物分组,进行等效剂量换算,分别从性别和年龄对抗精神病药物治疗的等效剂量差异性进行分析。结果:性别分组结果显示女性精神分裂症患者的利培酮组、联合药物组以及氯氮平组的平均有效剂量分别为(10.53±2.57) mg、(18.45±7.08) mg、(6.54±2.58) mg,显著低于男性精神分裂症患者(P<0.01或P<0.05)。年龄分组结果显示55～66岁年龄段的平均有效剂量最低,16～55岁年龄段男性患者用药剂量显著高于女性患者,差异具有统计学意义(P<0.001或P=0.001)。结论:性别以及年龄因素均可能对精神分裂症患者抗精神病药治疗剂量产生影响。     

精神分裂症患者治疗前血清MCP-1水平预测利培酮疗效

背景:精神分裂症是一种慢性致残性疾病,其发病及治疗可能与炎性细胞因子有关.目前细胞因子预测抗精神病药物疗效的研究尚少.目的:研究细胞因子对抗精神病药物疗效的预测作用.方法:采用横断面与自然观察随访相结合的方法,(1)对比精神分裂症患者组(n=64)基线期和正常对照组(n=53)血清IL-1β、TNF-α和MCP-1水平;(2)探索基线期细胞因子水平对奥氮平或利培酮单药治疗效果的影响.结果:(1)精神分裂症患者治疗前血清MCP-1水平明显高于健康对照组(t=2.62,p=0.010),IL-1β(t=1.43,p=0.154)、TNF-α(t=0.79,p=0.434)未见变化;(2)精神分裂症患者治疗前MCP-1水平与利培酮单药治疗4周后PANSS量表一般病理评分的减少量呈显著负相关(r=-0.658;p﹤0.001),但在奥氮平组中则未发现(r=-0.031;p=0.855);(3)纳入性别、年龄、受教育年限和BMI后等影响因素后,多元线性回归分析发现,基线血清MCP-1水平可作为利培酮单药治疗效果的独立预测因子(校正R2=0.409,β=-0.658,p﹤0.001).结论:MCP-1可能参与精神分裂症的发生,治疗前血清MCP-1水平可能是利培酮疗效预测的生物标记物.     

3种非典型抗精神病药对精神分裂症患者心电图的影响

目的:探讨3种非典型抗精神病药对精神分裂症患者心电图的影响。:方法:将270例精神分裂症患者随机分成3组,分别给予利培酮、阿立哌唑和齐拉西酮治疗,于治疗前和治疗2、4、8周进行心电图检查。结果:利培酮组、阿立哌唑组和齐拉西酮组的心电图异常率分别为27.8%、26.7%和22.2%。其中利培酮组与阿立派唑组女性异常率显著高于男性(P<0.05)。心电图改变主要为T波改变、窦性心动过速、窦性心动过缓、室性期前收缩、不完全右束支传导阻滞。结论:3种非典型抗精神病药对精神分裂症患者心电图均有影响,但轻而可逆。     

精神分裂症患者治疗前血清MCP-1水平预测利培酮疗效（英文）

背景:精神分裂症是一种慢性致残性疾病,其发病及治疗可能与炎性细胞因子有关。目前细胞因子预测抗精神病药物疗效的研究尚少。目的:研究细胞因子对抗精神病药物疗效的预测作用。方法:采用横断面与自然观察随访相结合的方法,(1)对比精神分裂症患者组(n=64)基线期和正常对照组(n=53)血清IL-1β、TNF-α和MCP-1水平;(2)探索基线期细胞因子水平对奥氮平或利培酮单药治疗效果的影响。结果:(1)精神分裂症患者治疗前血清MCP-1水平明显高于健康对照组(t=2.62,p=0.010),IL-1β(t=1.43,p=0.154)、TNF-α(t=0.79,p=0.434)未见变化;(2)精神分裂症患者治疗前MCP-1水平与利培酮单药治疗4周后PANSS量表一般病理评分的减少量呈显著负相关(r=-0.658;p﹤0.001),但在奥氮平组中则未发现(r=-0.031;p=0.855);(3)纳入性别、年龄、受教育年限和BMI后等影响因素后,多元线性回归分析发现,基线血清MCP-1水平可作为利培酮单药治疗效果的独立预测因子(校正R2=0.409,β=-0.658,p﹤0.001)。结论:MCP-1可能参与精神分裂症的发生,治疗前血清MCP-1水平可能是利培酮疗效预测的生物标记物。     

MicroRNA-134 plasma levels before and after treatment for bipolar mania

Studies have previously documented that microRNAs (miRNAs), with their key roles in regulating both synaptic plasticity and brain development, are candidate genetic contributors to the etiopathology of bipolar disorder (BD). Moreover, miRNA identified as targets for the actions of chronic lithium and VPA are known to play diverse and intriguing roles in brain function. In particular, the brain specific miR-134 has recently been identified as a potential regulator of dendritic spine volume and synapse formation. Recently, circulating miRNAs have been reported as promising biomarkers for various pathologic conditions. We assessed the hypothesis that miRNA-134 may be present and detectable in circulating blood, and that miRNA-134 may serve as a biomarker of mania episodes in BD. In the present study, we recruited 21 bipolar I, manic (DSM-IV) patients and controls matched by sex and age for quantification of miR-134 level in plasma using real-time RT-PCR method. We found that: Plasma miR-134 levels in drug-free, 2-week medicated, and 4-week medicated bipolar mania patients were significantly decreased when compared with controls, and the level was increased on following medication. Decreased circulating miR-134 level both in drug-free and medicated patients did presented negative correlation with the clinical scales. Overall, these results suggest that the decreased plasma miR-134 levels may be directly associated with the pathophysiology and severity of manic symptoms in BD. Plasma miRNA-134 in BD may be considered as a potential peripheral marker that can respond to acute manic episodes and associate with effective mood stabilizers treatment.     

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.     

Reduced plasma nitric oxide metabolites before and after antipsychotic treatment in patients with schizophrenia compared to controls

BACKGROUND: Nitric oxide (NO) is believed to have a role in the pathophysiology of schizophrenia. We examined plasma levels of NO metabolites in patients with schizophrenia and normal controls. We also determined the impact of 6-week risperidone treatment on circulating NO metabolites in patients with schizophrenia. METHOD: Plasma NO metabolite (NO(x)) levels were measured in 55 schizophrenia patients before and after 6-week treatment with risperidone and in 55 normal controls. Severity of schizophrenia and response to treatment were assessed with the positive and negative syndrome scale (PANSS) for schizophrenia. NO(x) levels were estimated by the Griess method. RESULTS: Pre-treatment plasma NO(x) levels in schizophrenia patients (8.97+/-6.74 micromol/L) were lower than those of normal controls (14.51+/-6.30 micromol/L) (p<0.01). Schizophrenia patients had lower post-treatment NO(x) levels (10.99+/-8.31 micromol/L) than those of normal controls (p<0.01). There was marginal significant change between plasma NO(x) levels before and after 6-week treatment (p=0.056). Moreover, in 37 treatment responders (>/=30% improvement in PANSS score), post-treatment plasma NO(x) significantly increased in comparison to pre-treatment NO(x) (p=0.028). CONCLUSIONS: Plasma levels of NO(x) in patients with schizophrenia were significantly lower than normal controls both before and after the treatment. Our findings suggest that the improvement of psychiatric symptoms can lead to partially normalize a deficiency of NO after treatment in schizophrenia patients. Our findings support the hypothesis that the NO system is dampened in schizophrenia.     

Increased neurotrophin-3 in drug-free subjects with bipolar disorder during manic and depressive episodes

Bipolar disorder (BD) has been increasingly associated with abnormalities in neuroplasticity. Previous studies demonstrated that neurotrophin-3 (NT-3) plays a role in the pathophysiology of mood disorders. The influence of medication in these studies has been considered a limitation. Thus, studies with drug-free vs. medicated patients are necessary to evaluate the role of medication in serum NT-3 levels. About 10 manic and 10 depressive drug-free, and 10 manic and 10 depressive medicated patients with BD type I were matched with 20 controls for sex and age. Patients were assessed using SCID-I, YMRS and HDRS. Serum NT-3 levels in drug-free and medicated patients is increased when compared with controls (2.51 ± 0.59, 2.56 ± 0.44 and 1.97 ± 0.33, respectively, p < 0.001 for drug-free/medicated vs. control). Serum NT-3 levels do not differ between medicated and drug-free patients. When analyzing patients according to mood states, serum NT-3 levels are increased in both manic and depressive episodes, as compared with controls (2.47 ± 0.43, 2.60 ± 0.59 and 1.97 ± 0.33, respectively, p < 0.001 for manic/depressive patients vs. controls). There is no difference in serum BDNF between manic and depressive patients. Results suggest that increased serum NT-3 levels in BD are likely to be associated with the pathophysiology of manic and depressive symptoms.     

Decreased brain-derived neurotrophic factor in medicated and drug-free bipolar patients

Bipolar disorder (BD) has been associated with abnormalities in neuroplasticity and previous studies suggest an important role for BDNF in the pathophysiology of BD. The confounding effect of the use of medication in these studies has been considered a limitation. Thus, studies with both drug-free and medicated patients are necessary to assess the role of medication in serum BDNF levels. Twenty-two manic and depressed drug-free and 22 medicated BD type I patients were matched to 22 controls according to sex and age in a cross-sectional study. BDNF serum levels were assessed using sandwich-ELISA. Serum BDNF levels in drug-free (0.23 ± 0.09), and medicated (0.29 ± 0.19) BD patients were decreased when compared to controls (0.40 ± 0.12) - drug-free/medicated vs. control p < 0.001. The BDNF levels did not differ between medicated and drug-free BD patients. When analyzing patients according to mood states, serum BDNF levels were lower in BD patients during both manic (0.28 ± 0.11) and depressive episodes (0.22 ± 0.17), as compared with healthy controls (0.40 ± 0.12) - manic/depressed patients vs. controls p < 0.001. Results suggest that the association of lower serum BDNF and BD mood episodes is kept even in medicated patients, which strengthens the notion that BDNF serum levels may be considered a biomarker of mood episodes in BD.     

自由基代谢与精神分裂症临床症状和药物治疗的关系

目的：探讨自由基代谢与精神分裂症临床症状和药物治疗的关系。方法：是否治疗的慢性精神分裂症患者各４０例分别评定定阳性和阴性症状量表（ＰＡＮＳＳ）,并测定膜脂质过氧化物丙二醛（ＭＤＡ）含量、铜／锌超氧化物歧化酶（Ｇｕ－ＺｎＳＯＤ）和谷胱苷肽过氧化物酶（ＧＳＨ－Ｐｘ）活性。结果：与健康对照组相比,未治疗组患者ＭＤＡ含量和ＧＳＨ－Ｐｘ活性显著增加,治疗组患者无显著改变;而两组患者ＳＯＤ活性显著降低;未治疗     

Plasma S-100B protein in Chinese patients with schizophrenia: comparison with healthy controls and effect of antipsychotics treatment

PURPOSE: To examine the possibility that structural damage to the brain may play a role in the pathogenesis of schizophrenia by measuring the level of plasma S-100B, a calcium-binding protein found predominantly in the cytosol of glial cells. METHOD: Fifty-seven Chinese psychiatric inpatients who met DSM-IV diagnosis of schizophrenia and 60 healthy controls were enrolled in the study. Patients were assessed with the Positive and Negative Symptoms Scale (PANSS) at admission and at 12 weeks after treatment. Plasma samples were collected from patients and controls and S-100B protein was assayed using ELISA. RESULTS: (1) 29 of 57 patients (50.9%) showed increased S-100B level compared to the mean level of 60 healthy controls (p<0.005) vs. only 1 of 60 (1.67%) controls. The S-100B levels of unmedicated (0.119+/-0.059microg/L) and medicated patients (0.117+/-.0.057microg/L) were significantly higher than controls (0.067+/-0.022microg/L, both p<0.001), and S-100B levels of unmedicated patients were higher than those of medicated patients (p=0.024); (2) at admission, S-100B level was positively correlated with total score of PANSS (r=0.269, p=0.043), especially with negative subscore of PANSS (r=0.306, p=0.021), but the correlation was no longer present after patients were treated by anti-psychotic agents. CONCLUSION: The S-100B levels of patients with schizophrenia are significantly higher than that of healthy controls, and the S-100B level is associated with severity of psychopathology, particularly negative symptoms, indicating that patients with schizophrenia may suffer structural damage to central nervous system. The concentration of S-100B may also be associated with treatment progress.     

抗精神病药致血糖改变与体重体脂指标关系

目的：分析首次治疗的精神分裂症患者抗精神病药(APS)急性期治疗期间血糖改变及其与体重体脂指标间的关系方法：测定46例患者(男27例，女19例)APS单药治疗10周前后空腹血糖和餐后2h血糖；观察治疗前后体重指数(BMI)和腰臀比率(WHR)，并采用磁共振测定其中40例患者治疗前后腹部脂肪分布结果：患者治疗10周后餐后2h血糖明显增高，葡萄糖耐量低减(IGT)发生率增加。治疗前餐后2h血糖水平与体重体脂指标呈正相关；治疗10周后，餐后2h血糖水平与体重体脂指标无相关。结论：APS急性期治疗可致精神分裂症患者血糖异常；血糖水平改变与体重增加及体脂沉积有关。     

Changes in plasma homovanillic acid concentrations in schizophrenic patients following neuroleptic discontinuation.

Changes in plasma levels of the dopamine metabolite homovanillic acid have been reported to correlate with changes in the severity of schizophrenic symptoms during neuroleptic administration and after neuroleptic discontinuation. This study examined the effects of discontinuation of neuroleptic treatment on plasma homovanillic acid levels in 23 patients with chronic schizophrenia. It was hypothesized that clinical decompensation would be associated with increased plasma homovanillic acid levels. Plasma homovanillic acid was measured during administration of neuroleptic medication and during a subsequent 6-week drug-free period. Nine patients decompensated during the drug-free period and 14 patients did not. Following drug discontinuation, plasma homovanillic acid concentrations were higher in schizophrenic patients who decompensated than in those who did not. Furthermore, peak plasma homovanillic acid elevation after discontinuation of neuroleptic medication was significantly correlated with peak Brief Psychiatric Rating Scale increase. The data suggest that, in some schizophrenic patients, symptomatic decompensation after discontinuation of neuroleptic treatment is associated with increases in dopamine turnover.     

Platelet alpha 2-adrenergic receptors in schizophrenic patients before and after phenothiazine treatment

The specific binding to isolated platelet membranes of 3H-clonidine, an alpha 2-adrenergic receptor partial agonist, and 3H-yohimbine, an alpha 2-adrenergic receptor antagonist, was measured in male, drug-free schizophrenic patients. The maximum number of binding sites (Bmax) for 3H-yohimbine was significantly lower in these patients than in normal subjects. Treatment with chlorpromazine (CPZ) for 2 weeks further decreased the Bmax for both ligands. Plasma catecholamine levels were determined before and after treatment. Before treatment, levels of dopamine and norepinephrine (NE) were within a normal range, while epinephrine (E) levels were significantly elevated. CPZ treatment significantly increased plasma NE levels, but decreased E levels to a normal range. These observations suggest that schizophrenia might be associated with abnormal noradrenergic function that is reflected by a decreased number of platelet alpha 2-adrenergic receptors.