高频重复经颅磁刺激治疗精神分裂症难治性阴性症状的随机双盲对照试验

目的:探讨双背侧前额叶高频重复经颅磁刺激(repetitive transcranial magnetic stimulation,rTMS)治疗精神分裂症难治性阴性症状的疗效和安全性,并观察不良反应。方法:本研究为双盲随机对照临床试验。研究对象来源于2002年11月1日至2003年12月31日期间就诊于北京大学第六医院和北京安定医院的门诊和住院患者,符合美国精神疾病诊断与统计手册第4版(Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition,DSM-IV)中精神分裂症诊断标准。23例以难治性阴性症状为主的精神分裂症患者随机分为rTMS治疗组(n=12)和对照组(n=11),分别给予10次20Hz rTMS真刺激和伪刺激治疗,治疗期间维持原有抗精神病药种类及剂量不变。采用阳性和阴性症状量表(Positive and Negative Syndrome Scale,PANSS)评估临床症状,采用治疗中需处理的不良反应症状量表(Treatment Emergent Symptom Scale,TESS)及其他检查评估不良反应。结果:23例患者均完成治疗。治疗组有效率高于对照组(34%vs.17%,P<0.05)。未观察到明显不良反应。结论:抗精神病药合并20Hz双背侧前额叶重复经颅磁刺激治疗精神分裂症难治性阴性症状有效、安全。     

低频重复经颅磁刺激治疗精神分裂症患者的顽固性幻听

目的:探讨左背外侧前额叶低频重复经颅磁刺激(rTMS)治疗精神分裂症患者顽固性幻听的临床疗效。方法:本研究为随机双盲对照研究。根据美国精神障碍诊断统计手册第4版(DSM-Ⅳ)的诊断标准,选取122例伴顽固性幻听的精神分裂症患者按2∶1随机分为治疗组(n=88)和对照组(n=34)。治疗组共接受6周的rTMS治疗,对照组接受伪刺激治疗。采用阳性和阴性症状量表(PANSS)、幻听量表(AHRS)、临床疗效总印象量表(CGI)评定临床症状,采用UKU副作用量表评估不良反应。对治疗组于治疗结束后在1、3、6个月进行随访。结果:共有108例(88.5%)患者完成治疗。两组间治疗6周末PANSS、AHRS、CGI量表得分差异无统计学意义(均P0.05)。但治疗组病程≤10年、病程10～20年的患者AHRS评分低于同病程的对照组(均P0.05),病程在20年以上的治疗组和对照组间差异无统计学意义(P=0.929,F=0.008)。治疗组除4例患者治疗时出现头痛外,余无不适主诉。结论:1Hz左背外侧前额叶低频rTMS治疗能减轻病程20年内的精神分裂症患者的顽固性幻听,可作为一种有效的安全性好的治疗手段。     

低频重复经颅磁刺激治疗左右利手精神分裂症幻听对照研究

目的:探讨低频重复经颅磁刺激治疗左、右利手精神分裂症幻听的疗效及安全性。方法:95例精神分裂症幻听按左、右利手分为两组,右利手组(72例)和左利手组(23例),均在原来抗精神病药治疗的基础上给予低频重复经颅磁刺激治疗共4周。治疗前及治疗后2、4周末分别用幻听评定量表(AHRS)评定幻听治疗效果,用阳性和阴性症状量表(PANSS)评定临床疗效,用副反应量表(TESS)评定不良反应。结果:治疗中左、右利手组各有1例脱落。4周末右利手组与左利手组AHRS比较有显著性差异(t=2.12,P0.05),右利手组减分高于左利手组。PANSS评分两组比较有显著性差异(t=2.30,P0.05)。不良反应两组间比较无显著性差异。结论:低频重复经颅磁刺激治疗右利手精神分裂症幻听好于左利手者。     

低频重复经颅磁刺激治疗精神分裂症幻听症状疗效的Meta分析

目的研究低频重复经颅磁刺激(rTMS)治疗精神分裂症幻听症状的疗效。方法计算机检索Pubmed、EMbase、Cochrane图书馆、CNKI、万方数据库、维普中文期刊数据库(VIP),收集1995-2014年2月关于rTMS治疗精神分裂症幻听症状的随机对照研究(RCTs)。主要研究指标为阳性与阴性症状量表(PANSS)的幻听评分及幻听评定量表(AHRS)。文献筛选、资料提取和方法学质量评价由两位研究者独立进行,以RevMan 5.1软件进行Meta分析。结果 17篇RCTs满足纳入标准,共包括786名受试者。Meta分析结果显示,两组之间的PANSS的幻听评分比较,均数差为-1.10,95%CI为[-1.65,-0.54],差异有统计学意义(Z=3.89,P=0.0001);两组之间的AHRS比较,均数差为-3.89,95%CI为[-5.72,-2.06],差异有统计学意义[Z=4.17,P0.00001]。结论低频rTMS对精神分裂症的幻听症状有效。     

低频重复经颅磁刺激对精神分裂症认知功能影响的随机双盲对照研究

目的评价低频重复经颅磁刺激(rTMS)对精神分裂症患者认知功能的影响及其安全性。方法 31例幻听症状突出的精神分裂症患者随机分组,治疗组21例接受真刺激联合药物治疗,对照组10例接受伪刺激联合药物治疗。用威斯康星卡片分类测验(WCST)、可反复测查的成套神经心理状态评估工具(RBANS)、持续操作测验(CPT)、Stroop字色干扰测验评价认知功能。治疗前后进行脑电图、心电图、血常规及生化检查,记录不良反应。采用重复测量方差分析比较两组各量表得分在6周内变化趋势的差异。结果治疗组与对照组相比,治疗10次后WCST的正确应答数显著提高(F=8.06,P0.01);RBANS的视觉广度分值显著改善(F=6.46,P0.05),言语功能分值也显著改善(F=6.24,P0.05)。治疗20次后WCST的正确应答数显著提高(F=3.36,P0.05),完成分类数(F=3.57,P0.05)也显著提高;RBANS的即刻记忆分值显著改善(F=4.50,P0.05),言语功能分值亦显著改善(F=6.67,P0.01)。rTMS治疗后脑电图无异常变化,未发现明显不良反应。结论低频rTMS可改善精神分裂症执行、记忆和言语功能且安全性好。     

重复经颅磁刺激治疗精神分裂症阴性症状的疗效分析

目的：探讨重复经颅磁刺激（rTMS）治疗精神分裂症阴性症状的效果和安全性。方法：25例以阴性症状为主的精神分裂症患者随机分为真刺激及伪刺激治疗组，共接受20次rTMS治疗。治疗开始及疗程结束时使用阳性和阴性症状量表（PANSS）及Anderson的阴性症状量表（SANS）评定疗效。结果：治疗结束后，真刺激组SANS总分减分率为52．38±14．48％，伪刺激组SANS总分减分率为1．84±3．34％，两组阴性症状的改善状况差异明显（P〈0．01）。治疗前后，rTMS真刺激组的PANSS总分和N分减分率也明显高于伪刺激组（P〈0．01）。结论：抗精神病药物治疗合并rTMS治疗对精神分裂症阴性症状有效。     

rTMS联合常规药物治疗精神分裂症伴强迫症的临床观察

目的:探讨rTMS联合常规药物治疗精神分裂症伴强迫症的影响。方法:选取我院2013年3月-2016年3月72例精神分裂症伴强迫症患者为研究对象,将纳入患者随机抽签分为观察组与对照组,每组36例。对照组在抗精神病治疗基础上加用氟西汀,观察组在对照组基础上给予高频率重复经颅磁刺激,比较血清素、磁共振氢质子波谱、事件相关电位P300、精神症状、强迫症状、不良反应。结果:观察组治疗4周后额叶氮-乙酰天门冬氨酸(NAA)/肌酸(Cr)、N1波幅、P3波幅显著高于对照组(t=2.436,3.201,4.774;P0.05)。观察组治疗4周后精神症状总分(PANSS)、强迫症状总分(DY-BOCS)显著低于对照组的(t=7.236,3.721;P0.01)。结论:高频率重复经颅磁刺激可以提高大脑皮质兴奋性,联合氟西汀可以有效改善精神分裂症状与强迫症状。     

重复经颅磁刺激和无抽搐电痉挛治疗抑郁症的初步比较

目的探讨重复经颅磁刺激和无抽搐电痉挛治疗抗抑郁疗效的差异。方法纳入分别接受重复经颅磁刺激治疗(rTMS组)和无抽搐电痉挛治疗(MECT组)的难治性抑郁症患者各30例,采用汉密尔顿抑郁量表在治疗前和治疗结束时评估患者临床症状,比较两组患者的疗效差异。结果 rTMS和MECT均能显著改善患者抑郁症状(rTMS组:t=0.34,P=0.02;MECT组:t=0.23,P=0.00)。rTMS组在汉密尔顿量表睡眠障碍因子分改善方面显著高于MECT组,差异有显著统计学意义(t=7.88,P=0.01),MECT在改善自杀因子方面优于rTMS,差异有显著统计学意义(t=3.87,P=0.00)。结论 rTMS和ECT在短期内均能有效改善抑郁症状,MECT的抗抑郁作用强于rTMS。在改善睡眠障碍方面,rTMS优于MECT;在改善自杀因子方面,MECT组作用更强。     

低频重复经颅磁刺激对重性抑郁症患者疗效分析

目的:探讨低频重复经颅磁刺激(rT MS)对重性抑郁症患者的疗效。方法:将60例艾司西酞普兰治疗的重性抑郁症患者随机分组,真刺激组(n=30)予右侧前额叶低频rT MS治疗,伪刺激组(n=30)予右侧前额叶伪刺激治疗。在治疗前及治疗4周末对两组评定汉密尔顿抑郁量表(HAMD)、副反应量表(TESS)。结果:治疗4周末,真刺激组、伪刺激组HAMD评分均较治疗前显著降低(t=20.629,17.970;P0.001)。治疗4周后,真刺激组HAMD分值低于伪刺激组(t=-2.580,P=0.012),真刺激组HAMD减分率(65%±11%)高于伪刺激组(54%±9%)(t=4.277,P=0.000)。真刺激组治愈率(36.7%)高于伪刺激组(13.3%),差异有统计学意义(χ2=4.356,P=0.037)。治疗过程中,真、伪刺激组的副反应发生率无显著差异。结论:低频rT MS可以安全有效地改善重性抑郁症患者的症状及提高临床治愈率。     

20Hz重复经颅磁刺激治疗改善难治性精神分裂症注意和执行功能的损害

目的探讨20Hz高频重复经颅磁刺激(rTMS)治疗对难治性精神分裂症患者认知功能的影响。方法 32例难治性精神分裂症患者随机分为两组,分别接受20Hz高频重复经颅磁刺激治疗(治疗组)与伪刺激治疗(对照组)2周。在治疗前和治疗结束时采用持续操作测验(CPT)和Wisconsin卡片分类测验(WCST)测定患者认知功能。结果 32例患者均完成治疗。治疗后与治疗前相比,CPT各项指标比较差异无显著性;20Hz rTMS对WCST各项指标的影响与空白对照组相比,WCST5(完成的分类数)治疗组治疗后增加,而对照组治疗后降低,两组相比有显著统计学意义(F=6.215,P=0.022)。结论 20Hz高频重复经颅磁刺激治疗可改善难治性精神分裂症患者的执行功能。     

Association between HLA-A1 allele and schizophrenia gene(s) in patients refractory to conventional neuroleptics but responsive to clozapine medication

Abstract: We report an association between HLA-A1 allele and a subgroup of schizophrenic patients refractory to conventional neuroleptic treatment but responsive to clozapine. The frequency of HLA-A1 was 58% among the schizophrenic patients not responding to conventional treatment but responsive to clozapine but only 10.5% among the patients responding to conventional neuroleptics. The HLA-A1 occurs in 20% of the random Finnish population. Our results indicate that HLA-A1 defines a subgroup of schizophrenic patients with a selective response to neuroleptics.     

Depressed Natural Killer Cell Activity in Schizophrenic Patients

Factors that suppress natural killer (NK) cell activity were examined in a random sample of 73 schizophrenic patients. NK activity in these patients were compared with 25 healthy age, sex and race matched controls. The mean percent of NK activity was 21% in the schizophrenic group compared with 30% percent in the controls. The difference between these two groups was statistically significant. The mean percent of NK activity in the chronic undifferentiated schizophrenic subgroup and schizoaffective subgroup were 20% and 22% respectively. The degree of suppression of NK activity in the chronic undifferentiated subgroup was higher than in the schizoaffective one, but the difference was not statistically significant. The two subgroups were comparable regarding other immune related variables such as total white cell count, neutrophils, lymphocytes, total protein, albumin, globulin, immunoglobulins and stress. The lower impairment of NK activity in the schizoaffective subgroup may be due to their exposure to lithium which can enhance immune functions. Factors associated with significant suppression of NK activity in schizophrenic patients were physical restraint, number of psychotropic medications, number of chronic non-psychiatric diagnoses and race. Psychosocial stressors were associated with suppression of NK activity but it was not statistically significant. Our results identify factors associated with reduced NK activity observed in certain schizophrenic patients and NK activity in these patients may be the result of interaction between various factors.     

Depressed Natural Killer Cell Activity in Schizophrenic Patients

Factors that suppress natural killer (NK) cell activity were examined in a random sample of 73 schizophrenic patients. NK activity in these patients were compared with 25 healthy age, sex and race matched controls. The mean percent of NK activity was 21% in the schizophrenic group compared with 30% percent in the controls. The difference between these two groups was statistically significant. The mean percent of NK activity in the chronic undifferentiated schizophrenic subgroup and schizoaffective subgroup were 20% and 22% respectively. The degree of suppression of NK activity in the chronic undifferentiated subgroup was higher than in the schizoaffective one, but the difference was not statistically significant. The two subgroups were comparable regarding other immune related variables such as total white cell count, neutrophils, lymphocytes, total protein, albumin, globulin, immunoglobulins and stress. The lower impairment of NK activity in the schizoaffective subgroup may be due to their exposure to lithium which can enhance immune functions. Factors associated with significant suppression of NK activity in schizophrenic patients were physical restraint, number of psychotropic medications, number of chronic non-psychiatric diagnoses and race. Psychosocial stressors were associated with suppression of NK activity but it was not statistically significant. Our results identify factors associated with reduced NK activity observed in certain schizophrenic patients and NK activity in these patients may be the result of interaction between various factors.     

Theory of mind impairments in schizophrenia: symptomatology, severity and specificity

BACKGROUND: Several studies have examined the ability of schizophrenic patients to represent mental states ('theory of mind': ToM). There is consensus that some patients have impaired ToM, but there is disagreement about the relation between ToM and symptomatology, and about the severity and specificity of the deficit. METHODS: Two first-order and one second-order false belief tests of ToM were given to groups of schizophrenic patients and psychiatric and normal controls. The relation between ToM and symptomatology was explored using regression and symptom subgroup analyses. Severity was investigated by using the same task methodology as in autism research, to enable direct comparison with that disorder. Specificity was investigated using matched control tasks which were as difficult as the ToM tasks, but did not require ToM. RESULTS: Symptom subgroup analysis showed that schizophrenic patients with behavioural signs were impaired relative to controls on ToM, and that remitted patients and a single case with passivity symptoms performed as well as controls. Regression analysis showed that ratings of behavioural signs predicted impaired ToM in schizophrenia. There was weak evidence that a subgroup with paranoid symptoms had ToM impairments, although these were associated with low IQ. Schizophrenic patients only showed ToM deficits on the second-order task. No impairments appeared on the matched control tasks which did not require ToM. CONCLUSIONS: There is a clear association between ToM impairment and behavioural signs in schizophrenia. Deficits in paranoid patients are harder to detect with current tasks and may be compensated for by IQ-dependent problem-solving skills. ToM impairments in schizophrenia are less severe than in autism, but are specific and not a reflection of general cognitive deficits.     

Dopamine transporter gene polymorphism and psychiatric symptoms seen in schizophrenic patients at their first episode

To investigate the possible role of the dopamine transporter (DAT) gene in determining the phenotype in human subjects, allele frequencies for the 40-bp variable number of tandem repeats (VNTR) polymorphism at this site were compared between 117 Japanese normal controls and 118 schizophrenic patients, including six subgroups: early-onset, those with a family history, and those suffering from one of the following psychiatric symptoms at their first episode: delusion and hallucination; disorganization; bizarre behavior; and negative symptoms. No significant differences were observed between the group as a whole or any subgroup of schizophrenic patients and controls. The results indicate that VNTR polymorphism in the DAT gene is unlikely to be a major contributor to any of the psychiatric parameters examined in the present population of schizophrenic subjects. © 1996 Wiley-Liss, Inc.     

Measuring IQ in schizophrenia research: an update of the Quick Test in estimating IQ decline

The WAIS-R measurement of IQ in schizophrenic patients is problematic: the Quick Test of Ammons and Ammons has been used as an alternative despite variability in the accuracy of its estimation of IQ in other groups. We have updated the Quick Test and compared our new version with the original in 44 schizophrenic patients, and both versions with the WAIS-R in a subgroup of 15 patients. Improving the Quick Test materials led to improvement in performance independent of long-term memory function: both versions overestimated WAISR IQ. A previous finding of very high correlation between WAIS-R IQ and Quick Test IQ estimate in schizophrenic patients was not replicated. IQ decline measured with the NART and the Quick Test was less than that using the NART and the WAIS-R. We conclude that the Quick Test has serious limitations as an estimate of IQ in schizophrenic patients, and will bias the assessment of IQ decline so that its extent is apparently less than in reality.     

Hla, and the response to treatment with gamma-type endorphins in schizophrenia

In order to investigate whether genetic factors are involved in the response of schizophrenic patients to treatment with gamma-type endorphins, we typed 32 Dutch schizophrenic patients for the HLA-A, -B, -C and -DR antigens. The total patient group showed an increase of HLA-Bw4 and HLA-Cw1. A subgroup of 20 paranoid patients showed an increase of HLA-Cw1 and a significant heterogeneity for the HLA-C locus. In 16 patients who responded moderately or markedly to treatment with gamma-type endorphins, an increase of HLA-B15/Cw3 and a decrease of HLA-B17 were found as compared to 16 patients with no or a slight response. Moreover, HLA-B15 was particularly increased in those patients who responded markedly and remained free of psychotic symptoms for a period of at least 6 months after treatment with gamma-type endorphins (RR = 24.6, Puncorr. = 0.0015). Our results suggest that genetic factors coded for within the HLA region are associated with paranoid schizophrenia, and that HLA-B15/Cw3 is associated with a marked and prolonged response to treatment with gamma-type endorphins.     

Monoamine oxidase, phenylethylamine, norepinephrine and schizophrenia

The chain of events from decreased MAO activity in the peripheral blood of certain schizophrenic patients, particularly paranoid patients, to in creased concentrations of PEA, to increased NE and NE turnover in the brain of schizophrenic patients, may prove not to be as closely linked as the current hypothesis and available data suggest. Nevertheless, the notion that this chain exists is testable and provides an integrated hypothesis of etiology for a subgroup of schizophrenic patients.     

Neuropsychological test performances of paranoid schizophrenic and brain-damaged patients.

Predicted that simple tests that require attention and motor speed would be able to differentiate paranoid schizophrenics from brain-damaged patients better than more complex, problem-solving neuropsychological tests. The strategy was to improve discrimination between schizophrenic and brain-damaged patients by selecting a schizophrenic subgroup with a recognized cognitive strong point. Fourteen organic, 14 paranoid schizophrenic, and 14 nonpsychotic psychiatric patients matched for sex, education, and IQ were tested. As predicted, the attention and speed measures differentiated the brain-damaged and paranoid groups, while the four more complex measures from the Halstead-Reitan Battery did not separate the groups. There were no significant differences between the two psychiatric groups.