帕罗西汀对慢性不可预见应激大鼠惊跳反射和弱刺激抑制影响的初步研究

目的 探讨慢性不可预见应激大鼠的听觉惊跳反射和弱刺激抑制变化情况以及帕罗西汀对其的影响.方法 将24只大鼠按随机数字表法分为阴性对照组(8只)、慢性不可预见应激组(8只)和帕罗西汀组(8只).阴性对照组:静养21 d后给予蒸馏水灌胃;慢性不可预见应激组:先给予慢性不可预见应激21d后再给予蒸馏水灌胃21 d;帕罗西汀组:先给予慢性不可预见应激21 d后再给予帕罗西汀灌胃21 d.3组大鼠均接受体质量测量、自发活动、糖水偏好、惊跳反射和弱刺激抑制测试.结果 (1)慢性不可预见应激组大鼠体质量[(380.50±22.23)g]、10 min旷场自发活动[ (5765.57 ±2942.28) mm]、糖水摄入量[(19.09 ±7.16) ml/kg]均低于阴性对照组[(426.38±33.73)g、(12 272.15±2343.02) mm(42.58±11.68) ml/kg,P＜0.01];帕罗西汀组体质量[ (353.62 ±29.37)g]低于阴性对照组(P＜0.01).(2)惊跳反射实验结果3组大鼠之间差异无统计学意义(P＞0.05).(3)慢性不可预见应激组大鼠弱刺激抑制[( 30.50±14.84)％]小于阴性对照组和帕罗西汀组[ (57.80±13.32)％、(42.32±15.82)％],帕罗西汀组弱刺激抑制小于阴性对照组,差异均有统计学意义(P ＜0.01);82 dB时的弱刺激抑制高于70、64、58 dB时的弱刺激抑制(P＜0.01);76 dB时的弱刺激抑制高于64、58 dB时的弱刺激抑制(P ＜0.01);70 dB时的弱刺激抑制高于58 dB时的弱刺激抑制(P＜0.05).结论 随着弱刺激强度增加,弱刺激抑制逐渐增加;慢性不可预见应激大鼠存在弱刺激抑制的缺失,帕罗西汀能够缓解这一状况.     

惊跳反射弱刺激抑制及P50在精神分裂症中的应用

目的 探讨精神分裂症患者的惊跳反射弱刺激抑制(PPI)的特点.方法 应用美国Nicolet Bravo脑电生理仪,采用听觉感觉刺激模式对30例精神分裂症患者和28名正常人做听觉PPI及P50检测.结果 病例组PPI低于正常对照组;病例组的S1-P50降低、S2-P50增高、P50抑制明显减弱、S1-S2和100 (1-S2/S1)均下降.结论 精神分裂症患者存在感觉运动门控缺陷,PPI可作为一项实验室指标用于临床.     

精神分裂症感觉运动门控及惊跳反射弱刺激抑制的研究

大脑对信息加工过程的异常是精神分裂症的主要特征，而感觉运动门控(sensorimotor gating SG；又称为感觉门控，sensory gating)的缺损是导致该异常的重要机制之一。SG是大脑一种正常功能，指大脑对感觉刺激反应的调节能力。SG缺损可导致大脑处于感觉淹没状态(即大脑接受了大量的感觉刺激但不能正常地对其进行加工的非正常状态)，使其认知破裂，乃至出现精神症状”。现有2种较为成熟的定量测定感觉滤过量(感觉门控的大小)的方法，     

惊跳反射弱刺激抑制(PPI)实验方法的建立与应用——附78例健康成人分析

目的利用惊跳反射弱刺激抑制(PPI)新技术探讨健康成人感觉门控(SG)的特征。方法应用德国Brain Products公司的脑电生理仪,对78名18~55岁健康成人受试者(男性43名,女性35名),作PPI测定,并于28天后随机抽取21名受试者重复测试PPI。结果 (1)21名受试者首次测试及28天后测试时PPI波幅及潜伏期比较差异不明显(P0.05);(2)本研究中健康成人PPI数值为61±29%;(3)PPI男女性别比较差异未达显著性(P0.05)。结论健康成人PPI可由弱-强刺激结合的被动注意PPI范式诱发,间隔一定时间后仍波形稳定,未发现明显性别差异。     

男性慢性精神分裂症患者血清同型半胱氨酸水平研究

<正>我们探索随着病程迁延血清Hcy水平在早发及非早发精神分裂症患者中变化及影响其关联因素,报告如下。1对象和方法为2011年10月在我院住院且长期服用抗精神药物治疗的男性慢性精神分裂症患者,共77例。入组标准:1符合国际疾病分类第10版精神分裂症诊断标准;2病程≥2年,且服药≥6个月,近期病情稳定;3年龄18~66岁。排除1心脏、肝脏、肾脏、内分泌、风湿、血液、消化道系统、营养不良     

精神分裂症患者听觉P300的初步观察

采用听觉识别法对24例精神分裂症患者与24名正常人进行事件相关电位P300对照研究。发现患者的P300潜伏期明显延长、且与思维障碍和敌对猜疑症状呈显著的正相关,波幅明显减低、与缺乏活力呈显著的负相关。表明精神分裂症患者存在信息加工过程障碍。认为P300作为精神分裂症亚型的生物学标化,值得进一步探讨。     

男性精神分裂症患者视觉诱发磁场的初步研究

目的:以脑磁图(MEG)研究精神分裂症患者视觉诱发磁场(VEFs)的特点. 方法:20例男性精神分裂症患者(患者组)和13名正常人(对照组),给予右眼左半垂直视野黑白翻转格图形视觉刺激,记录受试者VEFs的M100波形、潜伏期、振幅及激活脑区的等电流偶极(ECD)的磁源性影像(MSI)的XYZ值. 结果:所有受试者VEFs的最基本波形为M100,位于距状裂两侧的皮质.与对照组比较,患者组VEFs的M100波形存在异常,潜伏期明显延长,振幅显著降低(P均<0.05);且ECD的XYZ值显示其M100反应的ECD位置在X轴上分布偏移. 结论:MEG可检测出精神分裂症患者VEFs存在异常,其视觉皮质中枢功能亦存在异常.     

精神分裂症患者听觉P50诱发电位的研究

目的探讨精神分裂症患者听觉P50诱发电位的特征和意义.方法比较33例精神分裂症患者与35名正常人P50对条件-试验听觉刺激反应的差异.结果精神分裂症组呈现①条件刺激P50波幅为(2.94±1.7)μV,显著低于正常组(3.85±1.8)μV(P＜0.05).②P50抑制显著减弱,它包括试验/条件(T/C)比率显著增高,达0.83±0.2和试验刺激P50反应(T-P50)波幅升高,呈抑制显著不足.其P50抑制减弱与患者病程无关.结论精神分裂症患者存在感觉门能力不足,与对听觉刺激的神经非同步性反应有关,并造成感觉超载.它有可能成为精神分裂症心理生理学标记之一.     

住院男性慢性精神分裂症患者孤独感调查

目的 探讨住院男性慢性精神分裂症患者产生孤独感的相关因素,为住院慢性精神分裂症患者孤独感的预防提供参考.方法 对106例住院慢性男性精神分裂症患者进行UCLA、ESLI问卷调查.对产生孤独感的相关因素进行积差相关分析,方差分析,筛选产生孤独感的危险因素.结果 患者UCLA、ESLI得分较高,病程长、阴性症状重、疾病分型单纯型、自我效能差是孤独的主要相关危险因素.结论 住院慢性男性精神分裂症患者孤独感严重,应采取积极有效的防治措施,改善阴性症状,提高自我效能,以改善孤独感.     

高频重复经颅磁刺激对慢性精神分裂症患者认知功能的影响

目的：探讨高频重复经颅磁刺激（rTMS ）对慢性精神分裂症患者认知功能的影响。方法本研究为随机假刺激对照双盲随访临床试验。47例以阴性症状为主的慢性精神分裂症患者按随机数字表分为研究组（n ＝25）和对照组（n ＝22）,分别给予每周5次持续4周的10 Hz 110％ M T 的rTMS 真刺激和假刺激治疗;在基线期、4周末、8周末用阴性症状量表（SANS）、图形识别记忆（PRM ）分别评定患者阴性症状与认知功能,采用治疗不良反应量表（TESS）评估不良反应。结果研究组经治疗后 SANS 总分及各因子分均较基线时下降,而对照组仅 SANS 总分、情感平淡因子分及注意障碍因子分较基线时下降,差异有统计学意义（P ＜0．05）;且第8周末研究组 SANS 总分及除情感平淡因子分以外的其他因子分较第4周末相比下降,差异均有统计学意义（P ＜0．05）。研究组在治疗8周末时正确题数明显提高,选择时间和间隔时间同时明显缩短,组间不同时间点比较差异有统计学意义（P ＜0.05）,而对照组各时间点比较差异均无统计学意义（P ＞0．05）。结论 rTMS 辅助治疗可以改善慢性精神分裂症患者的认知功能,且效应延迟出现。     

Prepulse inhibition of the startle reflex in schizophrenia remains stable with short-term quetiapine

Purpose

To study the short-term effect of treatment with quetiapine on prepulse inhibition (PPI) deficits of the startle reflex in schizophrenia patients.

Subjects and methods

Using PPI, we studied a group of 21 schizophrenia patients and 16 controls. Seventeen of the patients were re-tested with PPI after 21 days of treatment with quetiapine.

Results

At baseline, an almost significant decrease in PPI was found in the patients as compared to the controls. PPI measurements did not change in the patients after 21 days of treatment with quetiapine, despite their clinical improvement.

Conclusion

Our results suggest that short-term quetiapine treatment may not modify PPI measures in schizophrenia patients.     

Uncontrollable voices and their relationship to gating deficits in schizophrenia

BACKGROUND: Prepulse inhibition (PPI) of the startle response refers to the ability of a weak prestimulus to transiently inhibit the response to a closely following strong sensory stimulus. This effect is reduced in a number of disorders known to be associated with impaired gating of sensory, cognitive or motor information. The aim of this study was to investigate PPI deficit in relation to the dimensions of auditory hallucinations in patients with schizophrenia or schizoaffective disorder. METHOD: PPI of the acoustically elicited eye blink startle response was measured electromyographically in 62 patients with schizophrenia (n=55) or schizoaffective disorder (n=7) (26 of 62 with current auditory hallucinations) and 22 healthy participants matched, on average, to age and sex of the patient group. RESULTS: Patients, as a group, showed reduced PPI compared to healthy participants. The presence of auditory hallucinations was associated with a marked PPI deficit if the patients felt that they had no control over their occurrence and that they were unable to dismiss them. Hearing voices with a high degree of negative content was associated with high mean startle amplitude in patients with current auditory hallucinations. CONCLUSIONS: Although auditory hallucinations in patients with schizophrenia are theorised to result from impaired monitoring of inner speech, the inability to consciously ignore them appears to be associated with a gating deficit. Hearing voices with negative content is associated with hyper-startle responding, possibly because such voices are threatening and thus provoke anxiety.     

Assessment of excitability in brainstem circuits mediating the blink reflex and the startle reaction

Excitability is probably the concept that fits better with the definition of the role of neurophysiology in the study of brainstem functions and circuits. Neurophysiological techniques are likely the best suited of all paraclinical tests for documenting the eventual excitability changes that may occur in certain physiological states and in many neurological disorders. The best known test of brainstem excitability is the blink reflex. While a single stimulus can already indicate the readiness of the interneuronal path and the facial motoneurons to fire, pairs of stimuli (conditioning and test) are suited to analyze the degree of excitability recovery after a single discharge. Another brainstem reflex circuit, which excitability testing can be of interest for physiological and clinical exams is the one involved in the startle reaction. The size of the responses and their habituation are the typical measures of excitability of the startle reflex circuit. Prepulse inhibition is a method to modulate both, the blink reflex and the startle reaction. It is defined as the inhibitory effect caused by a stimulus of an intensity low enough not to induce a response by itself on the response elicited by a subsequent stimulus. The circuits of the blink reflex, startle reaction and prepulse inhibition share some commonalities but they are different enough for the three techniques to provide unique, clinically relevant, information in certain conditions. The role of neurophysiology is not limited to testing those functions. It is important also for the assessment of many other circuits, such as those implicated in eye movements, vestibular reflexes, arousal, sleep, breathing, or autonomic reactions, which are not considered in this review.     

Cortical grey matter volume and sensorimotor gating in schizophrenia

Prepulse inhibition (PPI) of the startle response, a cross-species measure of sensorimotor gating, provides a valuable tool to study the known inability of a large proportion of individuals with schizophrenia to effectively screen out irrelevant sensory input. The cortico-striato-pallido-thalamic circuitry is thought to be responsible for modulation of PPI in experimental animals. The involvement of this circuitry in human PPI is supported by observations of deficient PPI in a number of neuropsychiatric disorders that are characterised by abnormalities at some level in this circuitry, and findings of recent functional neuroimaging studies in healthy participants. The current study sought to investigate the structural neural correlates of PPI in a sample of 42 stable male outpatients with schizophrenia. Participants underwent magnetic resonance imaging (MRI) at 1.5T and were assessed (off-line) on acoustic PPI using electromyographic recordings of the orbicularis oculi muscle beneath the right eye. Optimised volumetric voxel-based morphometry implemented in SPM2 was used to investigate the relationship of PPI (prepulse onset-to-pulse onset interval 120msec) to regional grey matter (GM) volumes. Significant positive correlations were obtained between PPI and GM volume in the dorsolateral prefrontal, middle frontal and the orbital/medial prefrontal cortices. Our findings are consistent with (a) previous suggestions of susceptibility of PPI to cognitive processes controlled in a 'top down' manner by the cortex and (b) the hypothesis that compromised neural resources in the frontal cortex contribute to reduced PPI in schizophrenia.     

Startle response models of sensorimotor gating and habituation deficits in schizophrenia

Studies of prepulse inhibition and habituation of startle responses elicited by intense stimuli provide some unusual opportunities for cross-species explorations of attentional deficits characteristic of schizophrenic patients. Schizophrenic patients exhibit deficits in both the prepulse inhibition of startle and the habituation of startle. The behavioral plasticity of startle responses and the comparability of the test paradigms used in rats and humans greatly facilitates the development of animal models of specifiable behavioral abnormalities in schizophrenic patients. This review describes two such examples of parallel animal and human models, one involving sensorimotor gating and the other examining behavioral habituation. Evidence is presented supporting the involvement of mesolimbic dopaminergic systems in the modulation of prepulse inhibition or sensorimotor gating and the importance of central serotonergic systems in the habituation of startle.     

Affective modulation of the startle reflex in schizophrenic patients

Startle-elicited blinks were measured during the presentation of affective slides in order to investigate emotional responsiveness in 24 male healthy subjects and 34 male schizophrenic patients. Although the two groups did not differ with regard to their subjective and autonomic responses to the slide stimuli, there was a significant difference between the groups in their responses to the startle probes. Patients rated low in affective expression showed a linear response pattern comparable to that of normal controls with largest amplitudes during unpleasant slides and smallest during pleasant slides. Patients without apparent deficit in affective expression showed a quadratic relationship with smaller blink amplitudes during both pleasant and unpleasant slides. Diminished affective expression rated on the basis of a clinical interview is not associated with a general attenuation of the blink reflex or of its modulation by exposure to emotional slides. Thus, we found no indication of an impairment in the perception of affective stimuli nor of reduced appreciation of pleasant stimuli (anhedonia) in these patients.     

Lack of relationship between acoustic startle and cognitive variables in schizophrenia and control subjects

Measures of acoustic startle such as prepulse inhibition (PPI) and startle latency have been found to be impaired in schizophrenia, and are commonly thought to be related to cognitive deficits in this disease. However, findings about the relationship between startle variables and cognitive performance have been equivocal. In this study, we examined correlations between startle measures (baseline startle magnitude, latency, habituation and PPI) and cognitive performance (using the Benton Visual Retention Test, Conner's Continuous Performance Test, California Verbal Learning Test, Finger Tapping Test, and Wisconsin Card Sort Test) in 107 schizophrenia patients and 94 healthy controls. Overall, there was a lack of any significant relationship between these constructs in both populations when correcting for multiple comparisons. This suggests that alterations in startle measures seen in schizophrenia may not reflect elements of information processing that cause cognitive deficits in the disease.     

DOI disrupts prepulse inhibition of startle in rats via 5-HT2A receptors in the ventral pallidum

Serotonin (5-HT)_2A receptors are known to be involved in prepulse inhibition of the startle response (PPI), a measure of sensorimotor inhibition that is deficient in schizophrenia, Huntington's disease, and obsessive compulsive disorder. In the present studies, the localization of the 5-HT_2A receptors responsible for modulating PPI was investigated using central injections of the hallucinogenic 5-HT₂ agonist DOI and the novel 5-HT_2A antagonist MDL 100,907. 5-HT_2A receptors are densely localized in the nucleus accumbens (NAC) and the ventral pallidum (VP), areas known to be important components of neural circuitry that mediates the ventral forebrain modulation of PPI. In the present studies, it was found that the infusion of DOI (0.0–5.0 μg/0.5 μl) into the VP disrupted PPI without having effects on startle reactivity. In contrast, similar infusions into the NAC had no effect on PPI or startle reactivity. The infusion of MDL 100,907 into the VP was found to increase PPI by itself and to attenuate the PPI-disruptive effects of systemically administered DOI. It is concluded that 5-HT_2A receptors within the VP are important for the modulation of PPI, presumably through interactions at intrinsic GABAergic or cholinergic interneurons.     

Inhibition of auditory evoked potentials and prepulse inhibition of startle in DBA/2J and DBA/2Hsd inbred mouse substrains

Previous data have shown differences among inbred mouse strains in sensory gating of auditory evoked potentials, prepulse inhibition (PPI) of startle, and startle amplitude. These measures of sensory and sensorimotor gating have both been proposed as models for genetic determinants of sensory processing abnormalities in patients with schizophrenia and their first-degree relatives. Data from our laboratory suggest that auditory evoked potentials of DBA/2J mice differ from those previously described for DBA/2Hsd. Therefore, we compared evoked potentials and PPI in these two closely related substrains based on the hypothesis that any observed endophenotypic differences are more likely to distinguish relevant from incidental genetic heterogeneity than similar approaches using inbred strains that vary across the entire genome. We found that DBA/2Hsd substrain exhibited reduced inhibition of evoked potentials and reduced startle relative to the DBA/2J substrain without alterations in auditory sensitivity, amplitude of evoked potentials or PPI of startle. These results suggest that gating of auditory evoked potentials and PPI of startle measure different aspects of neuronal function. The differences between the substrains might reflect genetic drift. Alternatively, differences could arise from different rearing environments or other non-genetic factors. Future studies will attempt to determine the cause of these differences in sensory and sensorimotor processing between these two closely related inbred mouse strains.