氯氮平、利培酮对精神分裂症患者白细胞介素-2的影响

目的 了解氯氮平、利培酮对首发精神分裂症偏执型患者血清白细胞介素-2(IL-2)的影响,并探讨IL-2与精神病理的关系。方法 对58例首发精神分裂症偏执型患者给予氯氮平或利培酮治疗,分别在治疗前和治疗后第4、8周末、6月末用酶联免疫吸附法检测血清IL-2水平,并用阳性和阴性症状量表(PANSS)评估精神症状及其变化。结果 两组患者治疗后第4、8周末血清IL-2水平均显著低于治疗前;不同药物对IL-2影响差异无显著性;治疗前IL-2水平与SPANSS总分、阳性症状分呈显著正相关;治疗后8周末血清IL-2减分值与阳性症状减分值呈显著正相关;利培酮组患者治疗后第8周末血清IL-2减分值与利培酮日量呈显著相关。结论 氯氮平和利培酮有相似的免疫抑制作用,血清IL-2与精神分裂症精神病理之间有一定的关系。     

偏执型分裂症外周血IL-1β、TNF-α和酪氨酸羟化酶mRNA表达水平与临床症状的关系

目的检测偏执型精神分裂症患者白介素-1β、肿瘤坏死因子-α和酪氨酸羟化酶（TH）的基因表达水平,探讨其与临床症状的关系。方法采用RT-PCR和半定量技术,分别检测39例偏执型精神分裂症患者和30例正常对照外周血单个核细胞IL-1β、TNF-α和TH的基因表达水平,同时应用PANSS量表评定偏执型精神分裂症患者临床症状。结果研究显示病例组的IL-1β、TNF-α、TH基因表达水平均显著高于正常对照组（P〈0.01）。且同时发现IL-1β（r=0.420）、TNF-α（r=0.430）基因表达水平与PANSS量表的一般病理症状分显著相关（P〈0.01）。结论偏执型精神分裂症患者可能存在致炎性细胞因子和儿茶酚胺类神经递质的过度表达;致炎性细胞因子可能参与偏执型精神分裂症一般病理症状的形成。     

精神分裂症偏执型患者血浆及脑脊液白细胞介素2,6及免疫球蛋白G水平的研究

目的　探讨首发精神分裂症偏执型患者血浆及脑脊液中白细胞介素 2 (IL 2 )、IL 6、免疫球蛋白G (IgG)水平的变化 ,及其与精神病理之间的关系。方法　患者组为 30例未用过抗精神病药治疗的精神分裂症偏执型患者 ,对照组为 2 0例无精神疾患的轻微脑外伤患者 ,以阳性和阴性症状量表 (PANSS)评定精神分裂症患者的精神症状 ,用酶联免疫吸附法检测IL 2、IL 6 ,用速率散射比浊法检测IgG。 结果　 (1)患者组血浆及脑脊液IL 2、IL 6和IgG均高于对照组 (P <0 0 1和P <0 0 5 )。(2 )在患者组中 ,血浆IL 6与血浆IgG(r =0 6 90 )和脑脊液IL 6 (r =0 4 2 5 )呈正相关 (P <0 0 1和P <0 0 5 ) ,血浆IgG与脑脊液IgG呈正相关 (r =0 4 0 9,P <0 0 5 ) ;脑脊液IL 6与脑脊液IgG呈正相关 (r =0 5 10 ,P <0 0 5 )。在对照组中 ,血浆IL 2与血浆IL 6 (r =0 5 0 4 ,P <0 0 5 )和IgG (r =0 74 0 ,P <0 0 1)呈正相关 ,血浆IL 6与血浆IgG(r=0 6 75 ,P <0 0 1)和脑脊液IL 6 (r =0 6 33,P <0 0 1)呈正相关 ,血浆IgG与脑脊液IgG(r =0 6 19,P <0 0 5 )呈正相关。 (3)血浆IL 2与P因子分呈正相关 (r =0 6 4 5 ,P =0 0 0 )。结论　首发精神分裂症偏执型患者处于免疫激活状态 ,IL 2、IL 6、IgG与精神病理之间存在一定的     

Effect of neuroleptic administration on serum levels of soluble IL-2 receptor-alpha and IL-1 receptor antagonist in schizophrenic patients

Activation of the inflammatory response system has been reported in schizophrenia. Levels of serum IL-1 receptor antagonist (IL-1ra) and soluble IL-2 receptor (sIL-2R(alpha)) were studied in 32 schizophrenic and 22 age- and sex-matched healthy subjects before and after an 8-week treatment protocol. Psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS). At weeks 0 and 8, sIL-2R(alpha) levels were significantly higher than in the schizophrenic patients, as well as in a neuroleptic-naive subgroup, than in controls. Patients' sIL-2R(alpha) levels did not vary significantly between weeks 0 and 8. IL-1ra levels in controls did not differ significantly from those in patients at week 0 but were significantly lower at week 8. The patients' serum IL-1ra levels varied significantly between weeks 0 and 8. IL-1ra levels were significantly higher in the subgroup of neuroleptic-naive patients at week 0 than in controls. Levels of sIL-2R(alpha) at week 0 were positively correlated with PANSS positive and negative symptom scores at week 8, and levels at week 8 were positively correlated with PANSS total, positive symptom, and negative symptom scores at week 8. IL-1ra levels at week 0 were positively correlated with PANSS scores at week 8. There were positive correlations between both delta (baseline values minus endline values) IL-1ra and delta sIL-2R(alpha) levels and delta PANSS negative symptoms. The results provide evidence for immune activation in some schizophrenic patients and suggest that medication differentially affects the production of sIL-2R(alpha) and IL-1ra.     

Neurological soft signs and positive treatment response to olanzapine in chronic schizophrenia

The goal of this study is to examine if Neurological Soft Signs (NSS) scores may improve on an 8-week olanzapine treatment in 10 patients with chronic schizophrenia. The patients were rated every 2 weeks on the Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression Scale (CGI). Baseline and endpoint NSS scores were evaluated by the Neurological Evaluation Scale (NES). The results demonstrated that baseline total PANSS and subscale scores of positive and general symptomatology, and baseline CGI scores were significantly reduced at the end of olanzapine treatment. There were no significant differences between baseline and endpoint subscale scores of negative symptomatology. We have also found no significant differences between baseline and endpoint total and subscale scores of NES. Baseline total scores of NES were significantly correlated only with negative schizophrenic symptoms at baseline. Our findings indicate that NSS may not improve in schizophrenic patients with olanzapine treatment.     

Higher fasting serum insulin levels are associated with a better psychopathology profile in acutely ill non-diabetic inpatients with schizophrenia

OBJECTIVE: Recent studies have suggested a beneficial role of insulin on brain function and psychological well-being. This study was undertaken to examine whether fasting serum insulin levels are associated with the psychopathology profile in a cross-sectional sample of acutely ill non-diabetic inpatients with schizophrenia. METHODS: Subjects were recruited from a county hospital. Each subject underwent a psychopathology assessment with the Positive and Negative Syndrome Scale (PANSS). A fasting blood sample was taken to measure serum insulin, plasma glucose and lipids. RESULTS: Twenty-six subjects (7 females, 19 males) were included in the study. Pearson correlation analysis showed significant inverse relationships between serum insulin level and PANSS-Total, Positive Symptom subscale, and General Psychopathology subscale scores (r=-0.41, p=0.037; r=-0.49, p=0.010; r=-0.45, p=0.023, respectively). However, there was no significant relationship between serum insulin level and PANSS-Negative Symptom subscale score (r=-0.13, p=0.53). Partial correlation analysis showed that the inverse relationships between serum insulin levels and PANSS-Total, Positive Symptom subscale, and General Psychopathology subscale scores became even stronger after controlling for potential confounding variables including age, gender, race, family history of mental illness, age of illness onset and body-mass index (BMI). CONCLUSIONS: Higher fasting serum insulin levels are associated with a better psychopathology profile in acutely ill non-diabetic inpatients with schizophrenia. It is speculated that insulin might improve clinical symptoms of schizophrenia by interacting with dopamine and other neurotransmitter systems.     

白介素—8和γ—干扰素在精神分裂症患者中表达水平的研究

目的 探讨白细胞介素—8和γ—干扰素表达水平与精神分裂症的关系.方法 对96例符合CCMD-3精神分裂症诊断标准的患者,用利培酮治疗.在治疗前后检测血清IL-8、INF-γ水平,在治疗前后评定PANSS和TESS量表,并采用酶联免疫试验(ELISA)检测血清IL-8和INF-γ含量.结果 首发精神分裂症血清IL-8明显高于正常组(P＜0.05),男女之间无差异;血清IL-8与病程、PANSS总分均呈正相关(r=0.627,0.592,P＜0.05),患者治疗前后血清INF-γ明显低于正常组,治疗前后变化无显著性差异(P＞0.05).结论 精神分裂症发生中IL-8产生增加并反映早期病情严重程度,患者INF-γ产生不足.     

白介素-6、10、12与精神分裂症临床特征的关系

目的 检测精神分裂症患者血浆IL-6、IL-10和IL-12水平,探讨其与精神分裂症临床特征的关系。方法 对57例精神分裂症患者和29例健康人,采用酶联免疫吸附法(ELSIA)检测其血浆IL-6、IL-10、IL-12水平,采用阳性和阴性症状评定量表(PANSS)评定患者的症状特征。结果 患者组血浆IL-12水平高于正常对照组(P<0.05),且与疾病的严重程度皇正相关;阴性症状组患者IL-6水平明显高于阳性症状组和正常对照组,而其IL-10水平则低于阳性症状组;急性或亚急性起病者血浆IL-10水平明显低于慢性起病组。 结论 精神分裂症存在细胞免疫异常,IL-12在精神分裂症的发病机制中起一定作用,IL-6和IL-10则与其部分临床特征有关。     

酸性神经酰胺酶基因与精神分裂症症状数量性状的关联研究

目的 探讨酸性神经酰胺酶基因(ASAH1)与精神分裂症症状数量性状的关联.方法 应用聚合酶链反应及限制性片段长度多态性技术,对254例精神分裂症患者ASAH1基因的3个单核苷酸多态性(rs3753118、rs3753116及rs7830490)进行检测;使用阳性和阴性症状量表(PANSS)评定患者疾病表型的数量性状.结果 (1)患者rs3753118位点3种基因型间的阳性症状分的差异有统计学意义(F=3.506,P＜0.05);rs3753116位点3种基因型间的PANSS总分及阴性症状分的差异均有统计学意义(F=3.548,P＜0.05;F=3.358,P＜0.05).经两两比较,rs3753118位点C/C基因型组患者的阳性症状分及一般精神病理分明显高于C/T基因型组患者;rs3753116位点G/G基因型组患者的PANSS总分及阴性症状分明显高于A/G基因型组患者,且G/G基因型组患者的阴性症状分明显高于A/A基因型组患者,差异均有统计学意义(P均＜0.05).(2)患者3个位点各等位基因间的PANSS量表评分的差异无统计学意义(P＞0.05).(3)患者rs3753118C-rs3753116G单体型者及rs3753118C-rs3753116G-rs7830490A单体型者,其PANSS总分及阴性症状分均明显高于参照单体型者,差异均有统计学意义(P均＜0.05).结论 ASAH1基因区域可能存在精神分裂症症状数量性状位点.     

Elevated interleukin-18 serum levels in chronic schizophrenia: Association with psychopathology

BackgroundSchizophrenia is associated with various abnormalities in the immune system including elevated levels of Interleukin-18 (IL-18), a potent inflammatory cytokine in T-helper 1 (Th1) responses. The aim of this study was to assess the clinical significance of serum IL-18 levels in various stages of schizophrenia.MethodsWe measured serum IL-18 levels using a sandwich enzyme-linked immunosorbent assay (ELISA) from 78 never-medicated first-episode schizophrenia, 79 medicated chronic schizophrenia and 78 healthy control subjects. The symptoms of schizophrenia were assessed by the Positive and Negative Syndrome Scale (PANSS).ResultsThe chronic patients had significantly greater serum IL-18 levels than both first-episode patients and controls. Serum IL-18 was also positively correlated with the PANSS general psychopathology subscore in chronic schizophrenic patients.ConclusionsOur results showed elevated IL-18 pathway activity may be involved in the psychopathology of schizophrenia.     

Elevated serum levels of C-reactive protein are associated with more severe psychopathology in a subgroup of patients with schizophrenia

The present study examined the hypothesis that elevated serum levels of C-reactive protein (CRP) would be associated with more severe clinical symptoms in patients with schizophrenia. Twenty-six inpatients with schizophrenia or schizoaffective disorder were enrolled. Serum levels of CRP were measured, and each patient was assessed with the Positive and Negative Syndrome Scale (PANSS). Subjects with CRP levels above the normal range (CRP>0.50 mg/dl, elevated CRP group, N=5) scored significantly higher than those with CRP levels in the normal range (CRP相似文献   

Effect of risperidone on serum cytokines

A variety of cytokines are dysregulated in schizophrenia, and some antipsychotic drugs effect cytokines. In order to examine the effect of risperidone on plasma cytokines, we measured the serum level of IL-1b, IL-2, IL-6, IL-12, and INF-g during acute states of illness, and after 4 weeks of treatment with risperidone in 19 schizophrenic patients. The patients' psychopathology was assessed by PANSS. Plasma IL-12 levels increased significantly after 4 weeks of treatment (p = .002). Plasma IL-b, IL-2, IL-6, and INF-g levels were not significantly different before and after treatment. There were no significant correlations between the changes in cytokine levels and the changes in PANSS scores. Increased IL-12 may contribute to activation of immune responses during treatment with risperidone. IL-12 may play an important role in immune responses related to neuropsychiatry.     

精神分裂症患者自评与他评症状量表差异的相关因素分析

目的:探讨精神分裂症患者自评与他评量表差异及与人口学资料、自知力、临床症状的相关因素分析。方法:对236例精神分裂症患者进行症状自评量表(SCL-90)精神病性症状分量表自评及阳性和阴性症状量表(PANSS)量表他评。比较自评与他评量表高差异与低差异两组间人口学资料、自知力、临床症状,并进行回归分析。结果:SCL-90精神病性症状分量表与PANSS总分有相关性(r=0.343,P0.05);受教育年限、阳性症状分和疾病认识分的差异进入Logistic回归模型。结论:阳性症状、疾病认识、受教育年限是患者自评与他评症状差异的相关因素。自评量表可以多角度地评估精神分裂症患者的症状。     

Thiol/Disulfide Homeostasis in Schizophrenic Patients

To determine serum thiol/disulfide homeostasis in schizophrenic patients. Serum native thiol, total thiol, and disulfide levels measuremented in the patients with 42 schizophrenia and 42 the healthy subjects. Serum native thiol, total thiol, and disulfide levels measuremented with a novel automated method. The thiol/disulfide ratio was also calculated. The Positive and Negative Syndrome Scale (PANSS) was used to assess the patients. The native thiol (p < 0.001) and total thiol (p < 0.001) levels, and the native thiol/total thiol (p = 0.018) ratio were significantly lower, whereas disulfide/native thiol (p = 0.002) and disulfide/total thiol (p = 0.002) ratio significantly increased in the schizophrenia patient group compared to the control group. A statistically significantly positive relationship was found between PANSS positive subscale with disulfide (r = 0.43, p = 0.01). Significantly positive relationships were found between PANSS total subscale with disulfide/total thiol (r = 0.308, p = 0.047). Our results suggest that the disulfide/thiol ratio is significantly greater in schizophrenia patients and disulfide/thiol ratio is closely related with the patients’ clinical symptoms.     

Changes in serum interleukin-2, -6, and -8 levels before and during treatment with risperidone and haloperidol: relationship to outcome in schizophrenia

BACKGROUND: Many studies have indicated that immune cytokines may be involved in the pathophysiology of schizophrenia. Recently, there have been reports that typical and atypical antipsychotic drugs may influence the levels of cytokines or cytokine receptors. The aim of this study was to compare the effect of typical and atypical antipsychotic drugs on serum interleukin-2 (IL-2), interleukin-6 (IL-6), and interleukin-8 (IL-8) and to investigate the relationship between the changes in cytokines and the therapeutic outcome in schizophrenia. METHOD: From April 1996 to August 1997, seventy-eight inpatients with a diagnosis of chronic schizophrenia (DSM-III-R) were randomly assigned to 12 weeks of treatment with 6 mg/day of risperidone or 20 mg/day of haloperidol. Clinical efficacy was determined using the Positive and Negative Syndrome Scale. Serum IL-2 was assayed by radioimmunometric assay, and serum IL-6 and IL-8 concentrations were measured by quantitative enzyme-linked immunosorbent assay in patients and 30 sex- and age-matched normal subjects. RESULTS: Both risperidone and haloperidol reduced the elevated serum IL-2 concentrations in schizophrenia, and no significant difference was noted in the reduction of serum IL-2 concentrations between risperidone and haloperidol treatment. Neither risperidone nor haloperidol showed significant influence on the higher serum IL-6 or IL-8 concentrations in schizophrenia. Correlations between serum IL-2 or IL-8 concentrations at baseline and the therapeutic outcome were observed, demonstrating that patients presenting with low concentrations of serum IL-2 or IL-8 at baseline showed greater improvement and patients presenting with higher serum IL-2 or IL-8 concentrations at baseline showed less improvement after treatment. CONCLUSIONS: Both typical and atypical anti-psychotic drugs may at least partially normalize abnormal immune alterations in schizophrenia. Some immune parameters at baseline may be useful for predicting the neuroleptic response of schizophrenic patients.     

Relationship between symptoms rated with the Positive and Negative Syndrome Scale and brain measures in schizophrenia.

The Positive and Negative Syndrome Scale (PANSS) was used to rate clinical symptoms in 42 inpatients with schizophrenia before they were examined by computed tomography. Significantly higher mean size of lateral and third ventricles, and higher mean cortical atrophy were found in schizophrenic patients compared with healthy control subjects. Ventricular enlargement and cortical atrophy were significantly related to low scores on the Composite subscale of the PANSS. Positive correlations were observed mainly with negative items such as blunted affect, emotional withdrawal, difficulties in abstract thinking, passive-apathetic social withdrawal, and lack of spontaneity of conversation. Additional positive correlations were observed with two items from the General Psychopathology subscale (mannerisms and disorientation). Inverse correlations were found with most positive items. These results suggest a relationship between brain structural abnormalities and the symptomatology of schizophrenia recorded with PANSS.     

精神分裂症神经内分泌激发试验研究

目的：通过内分泌激发实验,探讨慢性精神分裂症中枢５－ＨＴ功能状态。方法：对７８例精神分裂症、１８例正常对照进行帕罗西汀激发实验研究,以皮质醇和催乳素作为激发实验的应答指标。同时,对病人进行阳性和阴性症状评定量表（ＰＡＮＳＳ）测查。结果：治疗前精神分裂症组催乳素基础值明显低于对照组,帕罗西汀激发实验后催乳素释放增高,曲线下面积（ＡＵＣ）与对照组无显著关异。病人治疗前皮质醇基础值明显高于对照组,帕罗西     

首发精神分裂症患者血液中神经元特异性烯醇化酶和髓鞘碱性蛋白的改变

目的 通过测定首发精神分裂症患者髓鞘碱性蛋白(MBP)和神经元特异性烯醇化酶(NSE),探讨是否有神经系统损伤。方法 选择88例首发精神分裂症患者(患者组)和30例对照(对照组)测定血液中MBP和NSE,采用双抗体夹心酶标免疫分析法检测。并在入组第1天及第8周后分别评定阳性和阴性症状量表(PANSS)量表。结果 患者组MBP[(7.9±4.5)μg/L]和NSE[(19.4±6.9)μg/L]含量明显高于对照组[(4.3±0.4)μg/L,(8.0±2.8)μg/L],t:12.70,P<0.01;t=7.20,P<0.01。患者组MBP和NSE与PANSS总分减分率呈负相关(r=-0.236,P=0.025:r=-0.298,P=0.005)。结论 精神分裂症患者可能存在神经系统损伤,且受损程度可能与疗效有关。     

Bcl-2 associated with positive symptoms of schizophrenic patients in an acute phase

B cell lymphoma protein-2 (Bcl-2) may contribute to the pathophysiology of schizophrenia in the brain. The aim of this study was to investigate the serum levels of Bcl-2 in schizophrenic patients in an acute phase, and evaluate Bcl-2 level changes after antipsychotic treatment. We consecutively enrolled 41 schizophrenia patients in an acute phase; 28 were followed up with a 4-week antipsychotic treatment. Serum Bcl-2 levels were measured with assay kits. All patients were evaluated by examining the correlation between Bcl-2 levels and Positive and Negative Syndrome Scale (PANSS) scores, using Pearson correlation coefficients. In schizophrenic patients in an acute phase, positive PANSS subscores were significantly negatively correlated with Bcl-2 levels. In addition, we found Bcl-2 levels had a significantly negative correlation with PANSS total scores and positive subscores in male patients in an acute phase. Using the paired t-test, we found no significant changes in Bcl-2 levels in schizophrenia patients who had received the 4-week treatment with antipsychotic drugs (n=28). In conclusion, our results suggest that Bcl-2 might be an indicator of schizophrenia severity in the acute phase. In addition, Bcl-2 levels might be associated with positive symptoms in male patients with schizophrenia.     

Interaction of BDNF with cytokines in chronic schizophrenia

Brain-derived neurotrophic factor (BDNF) interacts with cytokines. Although both BDNF and cytokines occur at abnormal levels in schizophrenia patients, their interactions have not yet been examined. We therefore compared serum BDNF, TNF-α, interleukin (IL)-2, IL-6, and IL-8 levels in 92 chronically medicated schizophrenia patients and 60 healthy controls. We correlated these serum levels within these subject groups with each other and with clinical symptoms assessed according to the Positive and Negative Syndrome Scale (PANSS). Compared to the control group, the schizophrenia patients had significantly lower BDNF and TNF-α levels, and higher IL-2, IL-6, and IL-8 levels. The patients also showed a significant positive correlation between BDNF and both IL-2 and IL-8 levels, and low BDNF and TNF-α levels together were associated with poor performance on the PANSS cognitive factor. Thus, an interaction between cytokines and neurotrophic factors may be implicated in the pathophysiology of chronic schizophrenia. In particular, the cytokine TNF-α may interact with BNDF causing cognitive impairment.