重复经颅磁刺激治疗精神分裂症阴性症状的随机双盲研究

目的探讨重复经颅磁刺激（rTMS）治疗精神分裂症阴性症状的疗效。方法 30例精神分裂症患者被随机分为rTMS真刺激组（治疗组,15例）和rTMS伪刺激组（对照组,15例）,采用θ短阵快速脉冲刺激（TBS）模式刺激左侧前额叶背外侧皮质（DLPFC）,每周5次,共干预20次。于基线、治疗2周及治疗4周时应用阳性与阴性症状量表（PANSS）的阴性因子分和阴性症状量表（SANS）进行疗效评定。结果共有27例患者完成研究,对照组有3例脱落。经rTMS干预4周后,治疗组与对照组的PANSS阴性因子分减分值分别为（4.67±2.47）分和（2.33±1.87）分,两组比较有统计学差异（z=-2.41,P=0.016）;SANS总分减分值分别为（11.87±8.04）分和（5.92±6.47）分,两组比较有统计学差异（z=2.08,P=0.038）。根据PANSS阴性因子分评定,治疗组的有效率达到46.7%,对照组的有效率为16.7%;根据SANS总分评定治疗组的有效率达到46.7%,而对照组的有效率为8.3%;阴性症状的组间疗效差异有统计学意义（P〈0.05）。除了轻微的一过性头痛和入睡困难,未见有其他严重不良反应。结论 TBS模式可改善精神分裂症患者的阴性症状。     

重复经颅磁刺激对精神分裂症患者事件相关电位N400及血清脑源性神经营养因子水平的影响

目的:探讨重复经颅磁刺激(rTMS)对精神分裂症患者(患者组)事件相关脑电位(ERP)N400及血清脑源性神经营养因子(BDNF)的影响。方法:70例接受利培酮治疗的精神分裂症患者以随机数字表法分组,给予真刺激组(n=35)左侧背外侧前额叶rTMS治疗,伪刺激组(n=35)相应部位伪刺激治疗。采用酶联夹心免疫吸附法测定基线时及治疗5周的血清BDNF浓度,进行事件相关电位检测N400的潜伏期及波幅;并给予阳性与阴性症状量表(PANSS)及阴性症状量表(SANS)评估。结果:与治疗前相比,患者PANSS的阴性症状分、一般精神病理症状分及SANS分均明显下降(P均0.01)。与治疗前相比,治疗5周末2组(真刺激组和伪刺激组)血清BDNF水平显著升高(P0.05)。BDNF水平变化值与PANSS总分及各因子分变化值均无统计学相关性(P0.05)。治疗后真刺激组在额区N400中同音异形异义波幅和异音异形异义波幅,较治疗前显著提高(P均0.05)。结论:rTMS治疗可提高精神分裂症患者血清BDNF浓度,并有可能改善患者的认知功能。     

丁螺环酮辅助治疗慢性精神分裂症患者阴性症状的对照研究

目的:观察丁螺环酮辅助治疗慢性精神分裂症阴性症状的疗效及安全性。方法:将60例以阴性症状为主的慢性精神分裂症患者随机分为两组,在原抗精神病药基础上,分别联用丁螺环酮或安慰剂,疗程12周。在治疗前和治疗第4、8、12周末采用阳性和阴性症状量表(PANSS)及阴性症状量表(SANS)评估疗效,治疗中出现的症状量表(TESS)评估安全性。结果:研究组PANSS阴性因子总分、阴性因子各项症状分(除抽象思维困难和刻板思维)及SANS总分、各项分量表综合评价总分、分量表综合评价分(除思维贫乏)均在第12周末显著低于对照组(P0.05或P0.01);PANSS阴性因子总分、阴性因子各项症状分及SANS总分、各项分量表综合评价总分、分量表综合评价分从第8周末开始显著低于治疗前(P0.05或P0.01)。两组间不良反应差异无统计学意义(P0.05)。结论:联用丁螺环酮对治疗慢性精神分裂症阴性症状有增效作用,安全性好。     

文拉法辛对慢性精神分裂症的辅助治疗作用

目的:评价阿立哌唑合并文拉法辛缓释剂治疗慢性精神分裂症阴性症状的疗效和不良反应。方法:将78例慢性精神分裂症患者随机分为合用组(阿立哌唑合并文拉法辛缓释剂)和单用组(阿立哌唑),采用阳性症状和阴性症状量表(PANSS)、阴性症状量表(SANS)和治疗中出现的症状量表(TESS)于治疗前、治疗4、8、12周进行疗效及不良反应评定。结果:治疗8周合用组PANSS总分、阴性因子分,SANS总分及分量表分均比治疗前明显下降,且阴性因子分显著低于单用组。治疗后4、8、12周TESS评分,合用组低于单用组。结论:阿立哌唑合并文拉法辛缓释剂能明显改善慢性精神分裂症的阴性症状,且不良反应较少。     

重复经颅磁刺激对精神分裂症患者阴性症状和认知功能的疗效及安全性研究

目的:探讨重复经颅磁刺激(rTMS)改善精神分裂症患者阴性症状及认知功能的疗效及安全性。方法:入组2018年1月至2019年6月上海市民政第三精神卫生中心就诊的90例病程5年以下精神分裂症患者,给予利培酮药物维持治疗,后随机分为rTMS组(n=47)和伪刺激组(n=43),分别于治疗前、治疗4周末、治疗8周末对研究对象行阳性和阴性综合量表(PANSS)、神经心理状态评定量表(RBANS)测试,比较两组间各变量治疗前后的差异。结果:治疗4周后,rTMS组PANSS量表总分和阴性症状分均低于治疗前,且均低于伪刺激组,差异有统计学意义(P均<0.01)。对分组主效应方差分析发现rTMS组和伪刺激组在PANSS量表阴性分、总分2项和RBANS量表即刻记忆、视空间结构、语言功能、注意力、延迟记忆及RBANS总分6项有统计学差异(P均<0.01)。结论:rTMS治疗对精神分裂症患者阴性症状及认知功能具有改善作用,且疗效有持续效应,安全性好。     

奥氮平联用氟西汀治疗精神分裂症阴性症状的对照研究

目的 探讨奥氮平合并氟西汀治疗精神分裂症阴性症状的疗效和安全性.方法 将59例以阴性症状为主的精神分裂症患者随机分为研究组(奥氮平合用氟西汀治疗,30例)和对照组(单用奥氮平治疗,29例),于治疗前和治疗后第2、4、8、12周末使用阳性和阴性综合征量表(PANSS)和阴性症状量表(SANS)评定两组的疗效,药物治疗中需处理的不良反应症状量表(TESS)评定两组的不良反应.结果 治疗后第2周末研究组PANSS总分、阴性因子分较治疗前降低,差异有统计学意义(P＜0.05),治疗后第4周末研究组PANSS总分、阴性因子分及SANS总分、情感平淡因子分明显低于对照组,差异有统计学意义(P＜0.05,P＜0.01).两组TESS评分体质量改变差异有统计学意义(P＜0.05),余无明显差异.结论 奥氮平合并氟西汀能显著改善精神分裂症患者的阴性症状,且安全性好.     

20 Hz与10 Hz经颅磁刺激治疗精神分裂症阴性症状的研究

目的:比较20 Hz及10 Hz两种频率重复经颅磁刺激(rTMS)对精神分裂症阴性症状疗效及安全性。方法:以阴性症状为主住院精神分裂症患者62例，随机分为20 Hz组(32例)和10 Hz组(30例)。两组分别给予20 Hz和10 Hz rTMS刺激治疗4周，研究期间抗精神药种类及剂量不变。应用阳性和阴性症状量表(PANSS)在治疗前和治疗4周进行临床症状评定，治疗结束后第4、8、12周进行随访。应用治疗时出现的症状量表(TESS)在治疗2、4周进行不良反应评定。结果:治疗4周，两组PANSS总分及阴性症状分，阴性症状分中情感迟钝、情感退缩、情感交流障碍分明显低于治疗前(P<0.05)。治疗4周20 Hz组PANSS总分及阴性症状分较10 Hz组下降明显(P<0.05); 20 Hz组有效率高于10 Hz组(χ²=4.993,P=0.025)。治疗结束时及治疗结束后第4、8、12周两组PANSS总分及阴性症状分差异无统计学意义(P>0.05)。两组在治疗4周期间出现的不良反应均为轻度，患者均能耐受；20 Hz组发生率高于10 Hz组(χ^...     

重复经颅磁刺激治疗精神分裂症顽固性幻听对照研究

目的研究重复经颅磁刺激治疗精神分裂症幻听的临床疗效和安全性。方法伴顽固性幻听的精神分裂症患者随机分为研究组(n=60)和对照组(n=60)。在维持原抗精神病药物治疗基础上,研究组给予6周左侧颞顶叶的rTMS治疗,对照组给予伪刺激治疗。采用幻听量表(AHRS)、阳性症状和阴性症状量表(PANSS)、幻听量表(AHRS)评定临床疗效,采用不良反应量表(TESS)评估不良反应。结果 6周治疗后,研究组治疗幻听的有效率高于对照组(P<0.01),研究组AHRS、PANSS的总分和分量表评分均低于对照组,差异有统计学意义(P<0.05或0.01)。治疗中未见明显不良反应。结论左侧颞顶叶rTMS治疗能减轻精神分裂症患者的顽固性幻听。     

齐拉西酮治疗单纯型精神分裂症的对照研究

目的:比较齐拉西酮与利培酮治疗单纯型精神分裂症的疗效与不良反应.方法:将68例单纯型精神分裂症患者随机分成齐拉西酮与利培酮治疗组,疗程为12周,采用阳性与阴性症状量表(PANSS),阴性症状量表(SANS)临床疗效总评量表(CGI-GI)和在治疗中出现的症状鼍表(TESS)评定疗效和不良反应.结果:两组疗效相当,齐拉西酮不良反应明显低于利培酮.结论:齐拉西酮治疗单纯型精神分裂症疗效确切,不良反应轻微.     

利培酮合并舍曲林治疗慢性精神分裂症的对照研究

目的评价利培酮合并舍曲林治疗慢性精神分裂症阴性症状和副作用。方法将64例慢性精神分裂症患者随机分为单用组（利培酮组）与合用组（利培酮十舍曲林组）,采用阳性症状和阴性症状量表（PANSS）、阴性症状量表（SANS）和副反应量表（TESS）分别于治疗前、治疗后4、8、12周进行疗效及副反应评定。结果治疗8周后合用组PANSS总分、阴性因子分、SANS总分及分量表分均比治疗前明显下降,且阴性因子分显著低于单用组。治疗后4、8、12周TESS评分,合用组低于单用组。结论利培酮合并舍曲林能明显改善慢性分裂症,且副作用较少。     

Treatment of negative symptoms of schizophrenia using repetitive transcranial magnetic stimulation in a double-blind, randomized controlled study

OBJECTIVE: To verify whether high-frequency rTMS applied above the area of the left prefrontal cortex in 15 stimulation sessions with maximum stimulation intensity is able to modify negative symptoms of schizophrenia in a double-blind, randomized controlled study. METHODS: Twenty-two patients with schizophrenia stabilized on antipsychotic medication with prominent negative symptoms were included in the trial. They were divided into two groups: eleven were treated with effective rTMS and eleven with ineffective "sham" rTMS. The ineffectiveness of the sham rTMS was achieved through the stimulation coil position. Stimulation was applied to the left dorsolateral prefrontal cortex. The stimulation frequency was 10 Hz. Stimulation intensity was 110% of the motor threshold intensity. Each patient received 15 rTMS sessions on 15 consecutive working days. Each daily session consisted of 15 applications of 10-second duration and 30-second intervals between sequences. There were 1500 stimuli per session. RESULTS: During real rTMS treatment a statistically significant decrease of negative symptoms was found (approximately 29% reduction in the PANSS negative symptom subscale and 50% reduction in the SANS). No adverse events occurred during therapy except for a mild headaches. In sham rTMS treatment a decrease of negative symptoms was also identified, but to a lesser extent than in real rTMS (about 7% in negative subscale PANSS and 13% in SANS). The change in SANS achieved statistical significance. Mutual comparison revealed a greater decrease of negative symptoms in favor of real rTMS in contrast to sham rTMS. CONCLUSION: The augmentation of rTMS enabled patients to experience a significant decrease in the severity of the negative symptoms. Our results support the therapeutic potential of rTMS at higher frequency for negative symptoms of schizophrenia.     

Adjunctive memantine therapy for cognitive impairment in chronic schizophrenia: a placebo-controlled pilot study

Objective

To investigate the effects of memantine, an N-methyl-d-aspartate (NMDA) receptor antagonist, on cognitive impairments in patients with chronic schizophrenia.

Methods

A 12-week, placebo-controlled trial was conducted to determine the effectiveness of memantine as an adjunctive treatment with conventional antipsychotic medications in 26 patients with chronic schizophrenia. The subjects were evaluated with the Korean version of the Mini-Mental State Examination (K-MMSE), the Positive and Negative Syndrome Scale (PANSS), the Hamilton Rating Scale for Depression (HAM-D), and a standard neuropsychological screening test.

Results

Memantine treatment was not associated with significantly improved cognitive test scores compared with the placebo control treatment. An improvement in the scores on the PANSS negative subscale was noted with memantine, but it was not significant.

Conclusion

Adjunctive memantine treatment did not improve cognitive functioning or affect psychopathology in patients with chronic schizophrenia in the present study. Memantine, however, was tolerated well and did not exacerbate positive symptoms in patients with chronic schizophrenia.     

Phase 2 Trial of an Alpha-7 Nicotinic Receptor Agonist (TC-5619) in Negative and Cognitive Symptoms of Schizophrenia

Objectives:

This trial was conducted to test the effects of an alpha7 nicotinic receptor full agonist, TC-5619, on negative and cognitive symptoms in subjects with schizophrenia.

Methods:

In 64 sites in the United States, Russia, Ukraine, Hungary, Romania, and Serbia, 477 outpatients (18–65 years; male 62%; 55% tobacco users) with schizophrenia, treated with a new-generation antipsychotic, were randomized to 24 weeks of placebo (n = 235), TC-5619, 5mg (n = 121), or TC-5619, 50mg (n = 121), administered orally once daily. The primary efficacy measure was the Scale for the Assessment of Negative Symptoms (SANS) composite score. Key secondary measures were the Cogstate Schizophrenia Battery (CSB) composite score and the University of California San Diego Performance-Based Skills Assessment-Brief Version (UPSA-B) total score. Secondary measures included: Positive and Negative Syndrome Scale in Schizophrenia (PANSS) total and subscale scores, SANS domain scores, CSB item scores, Clinical Global Impression-Global Improvement (CGI-I) score, CGI-Severity (CGI-S) score, and Subject Global Impression-Cognition (SGI-Cog) total score.

Results:

SANS score showed no statistical benefit for TC-5619 vs placebo at week 24 (5mg, 2-tailed P = .159; 50mg, P = .689). Likewise, no scores of CSB, UPSA-B, PANSS, CGI-I, CGI-S, or SGI-Cog favored TC-5619 (P > .05). Sporadic statistical benefit favoring TC-5619 in some of these outcome measures were observed in tobacco users, but these benefits did not show concordance by dose, country, gender, or other relevant measures. TC-5619 was generally well tolerated.

Conclusion:

These results do not support a benefit of TC-5619 for negative or cognitive symptoms in schizophrenia.Key words: schizophrenia, negative symptoms, cognition     

脑源性神经营养因子C270T基因多态性与精神分裂症精神病理症状和认知功能的关系

Background

Findings from previous studies linking brain-derived neurotrophic factor (BDNF) and schizophrenia are inconsistent and few studies have assessed the relationship between BDNF C270T gene polymorphisms and the clinical and cognitive symptoms of schizophrenia.

Aim

Compare the prevalence of the BDNF C270T gene polymorphisms between patients with schizophrenia and controls and, in the patients, assess the relationship of genotypes to the severity of symptoms.

Methods

BDNF C270T genotype and allele frequency were measured using Polymerase Chain Reaction methods in 224 drug-free patients with schizophrenia and 220 controls. Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), and cognitive functioning was assessed using the Wisconsin Card Sorting Test (WCST) and the Trail Making Test (TMT). In the patient group, differences in severity of symptoms across the three genotypes (i.e., C/C, C/T, and T/T) of C270T were assessed using one-way analysis of variance.

Results

The frequency of the T allele was much higher in patients than in controls (15.6% vs. 4.3%, χ²=31.47, p<0.001) and the C/T genotype was more common among patients than controls (27.7% vs. 7.7%, χ²=34.93, p<0.001). Compared to controls, patients performed poorly on all the cognitive tests, but there were no significant differences in the cognitive measures between patients with the three different genotypes. The total PANSS score, the PANSS negative symptoms subscale score, and the PANSS general psychopathology subscale score were not significantly different between the three groups of patients. However, the PANSS positive symptoms subscale score showed a small, statistically significant elevation in the severity of positive symptoms in the C/T genotype compared to the C/C genotype.

Conclusion

We confirm previous findings about differences in the prevalence of the BDNF C270T gene polymorphisms in schizophrenia, but do not find strong evidence of a relationship between different genotypes and the severity of the clinical or cognitive symptoms of schizophrenia. Clinical and cognitive symptoms in schizophrenia fluctuate over the course of the illness and with treatment, so stable, individual-specific measures of these parameters (that is, traits) need to be identified before it will be possible to definitively assess their relationship to different genotypes.     

Adjunctive treatment with high frequency repetitive transcranial magnetic stimulation for the behavioral and psychological symptoms of patients with Alzheimer's disease: a randomized,double-blind,sham-controlled study

Background

Behavioral and psychological symptoms of dementia (BPSD) occur in 70-90% of patients at different stages of Alzheimer’s Disease (AD), but the available methods for managing these problems are of limited effectiveness.

Aim

Assess the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS), applied over the left dorsolateral prefrontal cortex (DLPFC), on BPSD and cognitive function in persons with AD.

Methods

Fifty-four patients with AD and accompanying BPSD were randomly divided into an intervention group (n=27) and a control group (n=27). In addition to standard antipsychotic treatment, the intervention group was treated with 20Hz rTMS five days a week for four weeks, while the control group was treated with sham rTMS.The Behavioral Pathology in Alzheimer''s Disease Rating Scale (BEHAVE-AD), the Alzheimer''s Disease Assessment Scale-Cognitive (ADAS-Cog), and the Treatment Emergent Symptom Scale (TESS) were administered by raters who were blind to the group assignment of patients before and after four weeks of treatment.

Results

Twenty-six subjects from each group completed the study. After four weeks of antipsychotic treatment with adjunctive real or sham rTMS treatment, the mean (sd) total BEHAVE-AD scores and mean total ADAS-Cog scores of both groups significantly decreased from baseline. After adjusting for baseline values, the intervention group had significantly lower scores (i.e., greater improvement) than the control group on the BEHAVE-AD total score, on five of the seven BEHAVE-AD factor scores (activity disturbances, diurnal rhythm, aggressiveness, affective disturbances, anxieties and phobias), on the ADAS-Cog total score, and on all four ADAS-Cog factor scores (memory, language, constructional praxis, and attention). The proportion of individuals whose behavioral symptoms met a predetermined level of improvement (i.e., a drop in BEHAVE-AD total score of > 30% from baseline) in the intervention group was greater than that in the control group (73.1% vs.42.3%, X²=5.04, p=0.025).

Conclusion

Compared to treatment of AD with low-dose antipsychotic medications alone, the combination of low-dose antipsychotic medication with adjunctive treatment with high frequency rTMS can significantly improve both cognitive functioning and the behavioral and psychological symptoms that often accompany AD.     

Deficits in facial emotion recognition in schizophrenia: a replication study with korean subjects

Objective

We investigated the deficit in the recognition of facial emotions in a sample of medicated, stable Korean patients with schizophrenia using Korean facial emotion pictures and examined whether the possible impairments would corroborate previous findings.

Methods

Fifty-five patients with schizophrenia and 62 healthy control subjects completed the Facial Affect Identification Test with a new set of 44 colored photographs of Korean faces including the six universal emotions as well as neutral faces.

Results

Korean patients with schizophrenia showed impairments in the recognition of sad, fearful, and angry faces [F(1,114)=6.26, p=0.014; F(1,114)=6.18, p=0.014; F(1,114)=9.28, p=0.003, respectively], but their accuracy was no different from that of controls in the recognition of happy emotions. Higher total and three subscale scores of the Positive and Negative Syndrome Scale (PANSS) correlated with worse performance on both angry and neutral faces. Correct responses on happy stimuli were negatively correlated with negative symptom scores of the PANSS. Patients with schizophrenia also exhibited different patterns of misidentification relative to normal controls.

Conclusion

These findings were consistent with previous studies carried out with different ethnic groups, suggesting cross-cultural similarities in facial recognition impairment in schizophrenia.     

Revisiting the therapeutic effect of rTMS on negative symptoms in schizophrenia: A meta-analysis

This study sought to determine the moderators in the treatment effect of repetitive transcranial magnetic stimulation (rTMS) on negative symptoms in schizophrenia. We performed a meta-analysis of prospective studies on the therapeutic application of rTMS in schizophrenia assessing the effects of both low-frequency and high-frequency rTMS on negative symptoms. Results indicate that rTMS is effective in alleviating negative symptoms in schizophrenia. The effect size was moderate (0.63 and 0.53, respectively). The effect size of rTMS on negative symptoms in sham-controlled trials was 0.80 as measured by the SANS and 0.41 as measured by the PANSS. A longer duration of illness was associated with poorer efficacy of rTMS on negative symptoms. A 10 Hz setting, at least 3 consecutive weeks of treatment, treatment site at the left dorsolateral prefrontal cortex (DLPFC) and a 110% motor threshold (MT) were found to be the best rTMS parameters for the treatment of negative symptoms. The results of our meta-analysis suggest that rTMS is an effective treatment option for negative symptoms in schizophrenia. The moderators of rTMS on negative symptoms included duration of illness, stimulus frequency, duration of illness, position and intensity of treatment as well as the type of outcome measures used.     

Repetitive transcranial magnetic stimulation of the right parietal cortex for comorbid generalized anxiety disorder and insomnia: A randomized,double-blind,sham-controlled pilot study

Background

Repetitive transcranial magnetic stimulation (rTMS) has been considered to be a promising technique for the treatment of neuropsychiatric disorders. However, little is known about the effectiveness of rTMS in the treatment of generalized anxiety disorder (GAD). Moreover, treatment data on comorbid GAD and insomnia remain lacking. The aim of this study was to examine the therapeutic effects of 1?Hz rTMS applied over the right parietal lobe on both anxiety and insomnia symptoms in patients with comorbid GAD and insomnia.

Adjunctive treatment of bimodal repetitive transcranial magnetic stimulation (rTMS) in pharmacologically non-responsive patients with schizophrenia: a preliminary study

Objectives

We evaluated the efficacy of bimodal repetitive transcranial magnetic stimulation (rTMS) in treating pharmacologically non-responsive patients with schizophrenia.

Methods

Ten patients with DSM-IV schizophrenia, unresponsive to pharmacological treatment, underwent treatment with 15 rTMS sessions, as an adjunctive therapy, for three weeks. Each session comprised 40 trains, beginning every 30 s: 20 trains of 10 Hz rTMS to the left dorsolateral prefrontal cortex (DLPFC) with a 3-s duration and 20 trains of 1 Hz rTMS to the left temporoparietal cortex (TPC) with a 30-s duration. We assessed patients via the Positive and Negative Syndrome Scale (PANSS) and Korean Version of the Calgary Depression Scale for Schizophrenia (K-CDSS), at five time points: baseline, Days 8, 15, and 22, and 1 week after final treatment (Day 29). Patients who agreed to take neurocognitive tests underwent neurocognitive function evaluations at baseline and 1 week after final treatment.

Results

At Day 29, all PANSS subscale scores in had decreased significantly compared to baseline (Z = − 2.214, p = 0.027, positive; Z = − 2.132, p = 0.033, negative; Z = − 2.023, p = 0.043, general pathology; Z = − 2.371, p = 0.018, total). Effect over time was significant for the PANSS positive and negative subscale scores and total score (χ² = 13.35, p = 0.010; χ² = 10.27, p = 0.036; and χ² = 16.50, p = 0.002, respectively) but not for the general pathology subscale. Among the neurocognitive tests, the fourth and fifth trials and total K-AVLT scores showed significant increases (Z = − 2.041, p = 0.041; Z = − 2.251, p = 0.024; and Z = − 2.201, p = 0.028, respectively), suggesting improvement in short-term auditory verbal memory.

Conclusions

Bimodal rTMS stimulation of left DLPFC and left TPC induced clinical improvement in pharmacologically non-responsive schizophrenia patients and may have improved their short-term verbal memories.