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1.
Wei Q Kang Z Diao F Shan B Li L Zheng L Guo X Liu C Zhang J Zhao J 《Progress in neuro-psychopharmacology & biological psychiatry》2012,36(1):122-127
Background
ZNF804A gene polymorphism rs1344706, the first genetic risk variant to achieve genome wide significance for schizophrenia, has been linked to neural functional connectivity. Dysconnectivity of WM may be the primary pathological mechanism of schizophrenia. Association of this variant with regional WM density has not been investigated in schizophrenic patients.Methods
69 healthy controls and 80 patients with schizophrenia underwent genotyping of rs1344706 SNPs, and were examined for WM density (T1-weighted MRI). The association of rs1344706 with WM changes in schizophrenia patients and healthy controls was analyzed using a full-factorial 2 × 2 analysis of variance.Results
1. There was an interaction on WM density in the left prefrontal lobe between the rs1344706 genotype and schizophrenic diagnosis, where the risk T allele carriers presented higher WM density in the schizophrenia patients and lower WM density in healthy controls in comparison with the non-risk allele carriers.2. The risk allele was associated with an increased WM density of the bilateral hippocampus in both the patients and the healthy group.Limitation
The influence of antipsychotics to the white matter in schizophrenic patients was not fully eliminated.Conclusions
The ZNF804A variant may confer risk for schizophrenia by exerting its effects on the WM in the left prefrontal lobe together with other risk factors for schizophrenia. 相似文献2.
Chen CH Lu ML Kuo PH Chen PY Chiu CC Kao CF Huang MC 《Progress in neuro-psychopharmacology & biological psychiatry》2011,35(1):239-245
Objective
Metabolic syndrome (MS) is a major health problem in schizophrenic patients. Peroxisome proliferator-activated receptor γ2 (PPARγ2) is one of the candidate genes responsible for the liability to metabolic problems. In this study, we investigated the effect of the PPARγ2 gene Pro12Ala and C161T polymorphisms on metabolic adversities in patients with schizophrenia or schizoaffective disorder.Methods
Metabolic profiles and PPARγ2 gene polymorphisms were determined in 600 patients (309 men and 291 women) with a clinical diagnosis of schizophrenia or schizoaffective disorder. Metabolic indices and components of MS were compared between patients with different Pro12Ala or C161T genotypes.Results
In the whole population, the allele frequency of 12Ala and 161T was 4.4% and 24.7% respectively. Both polymorphisms had no significant effect on obesity or metabolic-related traits. However, following gender stratification of the data, we found female 12Ala allele carriers were at greater risk of developing abdominal obesity (OR = 4.0, 95% CI = 1.1-14.2, p = 0.04) and hypertension (OR = 2.9, 95% CI = 1.2-7.4, p = 0.02) than female 12Ala allele non-carriers. Male 161T allele carriers had lower insulin levels (p = 0.02) and lower high-density lipoprotein cholesterol (HDL-C) (p = 0.05) levels than male 161T allele non-carriers. Moreover, female 161T allele carriers had higher body weight (p = 0.04), waist circumference (p = 0.05), and systolic blood pressure (p = 0.01), and were at greater risk of developing hypertension (OR = 2.0, 95% CI = 1.1-3.5, p = 0.02). Haplotype analyses showed that PPARγ2 gene polymorphisms were significantly associated with HDL-C level in men and blood pressure in women.Conclusions
We did not find an association of PPARγ2 gene polymorphisms with MS or obesity in our schizophrenia sample. But further analyses by gender stratification revealed gender-specific differences in the effect of different PPARγ2 genotypes on certain metabolic adversities in these patients. 相似文献3.
Zhou J Huang Y Huang RS Wang F Xu L Le Y Yang X Xu W Huang X Lian J Duan S 《Thrombosis research》2012,130(4):602-606
Introduction
Peden et al. have revealed a significant association between four new risk loci and coronary heart disease (CHD) in Europeans and South Asians. The goal of this study is to evaluate the contribution of these genetic loci to CHD risk in Han Chinese.Methods
We recruited 161 CHD patients and 112 controls proved by angiography originated from Ningbo in the Eastern China, and performed a case-control association study of the four significant SNPs.Results
Among the four tested SNPs, we found a significant association of rs974819 in PDGFD gene with CHD (allele p = 0.04; OR = 1.45, 95% CI = 1.02 - 2.08) and the allele A/G of rs974819 shows significant difference in females (allele p = 0.04; OR = 1.83, 95% CI = 1.01 - 3.31). A further meta-analysis showed that rs974819 of PDGFD gene was significantly associated with an increasing risk of CHD (OR = 1.08, 95% CI = 1.05 - 1.11) in both Europeans and South Asians including Han Chinese.Conclusions
Our findings suggests that rs974819 of PDGFD is also a CHD risk factor in Han Chinese. In addition, it presents a sex-dependent genetic effect. 相似文献4.
Introduction
Hirudin is a direct thrombin inhibitor that has potential mechanistic advantages over indirect inhibitors. Peptides containing the RGD motif competitively inhibit binding of fibrinogen to glycoprotein IIb/IIIa on platelets, thus inhibiting platelet aggregation. A novel hirudin derivative, recombinant RGD-hirudin (r-RGD-hirudin), was engineered by fusing the tripeptide RGD sequence to the native hirudin. We tested the antithrombotic effect of r-RGD-hirudin using a carotid artery reconstruction model in rabbits.Materials and methods
A fusion gene encoding r-RGD-hirudin was constructed and expressed at high levels in Pichia pastoris. Following traumatic injury and anastomosis, 42 New Zealand White rabbits were randomized to receive normal saline, abciximab, wild-type hirudin, or r-RGD-hirudin. Fibrinogen concentration, aPTT, TT, PT, and PAGm were measured prior to and following the operation. Carotid angiography and pathological examination of the anastomotic site were performed to compare patency rates among the groups.Results
The r-RGD-hirudin significantly prolonged aPTT, TT, PT and inhibited PAGm following carotid anastomosis in rabbits. The median dose of r-RGD-hirudin (0.5 mg/kg) had a therapeutic effect equal to that of wild-type hirudin (1.0 mg/kg) and higher than that of abciximab (0.2 mg/kg) with regard to patency rates.Conclusions
Compared to wild-type hirudin or antiplatelet agent, the novel anticoagulant, r-RGD-hirudin was capable of inhibiting both thrombin activity and platelet aggregation, and was demonstrated to be effective in the prevention of thrombosis. 相似文献5.
Otowa T Kawamura Y Sugaya N Yoshida E Shimada T Liu X Tochigi M Umekage T Miyagawa T Nishida N Kaiya H Okazaki Y Tokunaga K Sasaki T 《Progress in neuro-psychopharmacology & biological psychiatry》2011,35(2):545-549
Background
Panic disorder (PD) is a severe and chronic psychiatric disorder with genetic components underlying in its etiology. The Phosphodiesterase 4B (PDE4B) gene has been reported to be associated with several psychiatric disorders. Several studies indicated that PDE4B may be involved in the regulation of anxiety and depression. Therefore, we investigate the association of PDE4B with PD in the Japanese population.Methods
We genotyped 14 single nucleotide polymorphisms (SNPs) of PDE4B in 231 PD cases (85 males and 146 females) and 407 controls (162 males and 245 females). Differences in the genotype, allele and haplotype frequencies between the two groups were compared.Results
We found a significant association between PDE4B and PD in the haplotype analysis (haplotype C-T-T-A, permutation P = 0.031, OR = 1.81, 95% CI = 1.30-2.51). Sex-specific analyses demonstrated that PDE4B was associated with PD in females in the allele/genotype and haplotype analyses (rs10454453, allele P = 0.042, genotype P = 0.0034; haplotype C-T-T-A, permutation P = 0.028).Conclusion
Our results suggest that PDE4B may play a role in the pathophysiology of PD in the Japanese population. Replication studies using larger samples will be needed for more reliable conclusions. 相似文献6.
Anindya Dasgupta Om Prakash Singh Jayanta Kumar Rout Tanmay Saha Sonai Mandal 《Progress in neuro-psychopharmacology & biological psychiatry》2010
Objectives
Several studies have suggested insulin resistance related to dyslipidemia and body weight in drug treated schizophrenia patients. Although, insulin resistance or impaired glucose tolerance is also reported in antipsychotic naïve schizophrenia patients, their relationship with dyslipidemic changes and body weight is not well established. The present study was undertaken to examine insulin resistance in antipsychotic naïve schizophrenia patients of this region and to evaluate any association between lipid parameters and body weight with their insulin resistance, if any.Method
Plasma glucose, total serum cholesterol and its LDL, HDL fractions, and serum insulin levels were measured from fasting blood samples of newly diagnosed, antipsychotic naïve schizophrenia patients (n = 30) and matched control group (n = 25) in a hospital based case control study. Homoeostatic model assessment (HOMA) was done to evaluate insulin resistance.Results
Means of plasma glucose, total serum cholesterol and its LDL, HDL fractions did not vary significantly (p > 0.05) between cases and control. Insulin resistance was significantly increased (p < 0.05) in drug naïve cases. Multiple linear regression analyses did not show any association (p > 0.05) between insulin resistance and lipid parameters.Conclusions
Newly diagnosed schizophrenia patients were more prone to insulin resistance in our study population. This was not associated with any dyslipidemic changes as the lipid parameters were not elevated in them compared to the healthy controls. It was not dyslipidemia, but some other common genetic or risk factors that might be responsible for the increased insulin resistance in antipsychotic naïve schizophrenia patients in our study population. 相似文献7.
Martínez-Ortega JM Carretero MD Gutiérrez-Rojas L Díaz-Atienza F Jurado D Gurpegui M 《Progress in neuro-psychopharmacology & biological psychiatry》2011,35(7):1780-1784
Objective
Despite the fact that association between winter birth excess and schizophrenia in the northern Hemisphere is well established, possible sex or birth-cohort differences in this winter birth excess remain unclear. We aimed to evaluate sex and birth-cohort differences in the seasonal birth distribution of patients with schizophrenia or non-schizophrenic psychosis.Method
The sample included 321 ICD-10 schizophrenia and 294 non-schizophrenic psychosis patients consecutively admitted into a psychiatric hospitalization unit in Granada, southern Spain, during a nine-year period (1998-2006). The distribution of births among the general population born over the same period as the patients was calculated.Results
Among schizophrenia males (n = 258), it was possible to demonstrate that the observed proportion of winter birth (December, January or February) was significantly higher than expected. Among schizophrenia females (n = 63), although proportions were as in males and the effect size of the difference between observed and expected winter births was not lower than for men, only a statistical trend could be demonstrated. Among patients with non-schizophrenic psychosis, the observed proportion of winter birth was significantly higher than expected in women, but not in men. The sex-adjusted proportion of winter birth among schizophrenia patients born in the 1940's (a time period characterized by poor economy and widespread food restrictions because of the Spanish post-civil-war period) was significantly higher than among those born later; a difference that does not occur among patients with a non-schizophrenic psychosis.Conclusions
Among schizophrenia patients born in winter there appear to be slight sex-differences and strong birth-cohort differences, possibly due to epidemiological factors such as poverty or maternal nutritional deprivation. Epidemiological findings related to winter birth excess among patients with schizophrenia must be identified in longitudinal studies. 相似文献8.
Abbott C Juárez M White T Gollub RL Pearlson GD Bustillo J Lauriello J Ho B Bockholt HJ Clark VP Magnotta V Calhoun VD 《Progress in neuro-psychopharmacology & biological psychiatry》2011,35(2):473-482
Background
The effect of antipsychotics on the blood oxygen level dependent signal in schizophrenia is poorly understood. The purpose of the present investigation is to examine the effect of antipsychotic medication on independent neural networks during a motor task in a large, multi-site functional magnetic resonance imaging investigation.Methods
Seventy-nine medicated patients with schizophrenia and 114 comparison subjects from the Mind Clinical Imaging Consortium database completed a paced, auditory motor task during functional magnetic resonance imaging (fMRI). Independent component analysis identified temporally cohesive but spatially distributed neural networks. The independent component analysis time course was regressed with a model time course of the experimental design. The resulting beta weights were evaluated for group comparisons and correlations with chlorpromazine equivalents.Results
Group differences between patients and comparison subjects were evident in the cortical and subcortical motor networks, default mode networks, and attentional networks. The chlorpromazine equivalents correlated with the unimotor/bitemporal (rho = − 0.32, P = 0.0039), motor/caudate (rho = − 0.22, P = 0.046), posterior default mode (rho = 0.26, P = 0.020), and anterior default mode networks (rho = 0.24, P = 0.03). Patients on typical antipsychotics also had less positive modulation of the motor/caudate network relative to patients on atypical antipsychotics (t77 = 2.01, P = 0.048).Conclusion
The results suggest that antipsychotic dose diminishes neural activation in motor (cortical and subcortical) and default mode networks in patients with schizophrenia. The higher potency, typical antipsychotics also diminish positive modulation in subcortical motor networks. Antipsychotics may be a potential confound limiting interpretation of fMRI studies on the disease process in medicated patients with schizophrenia. 相似文献9.
Introduction
In patients with metabolic syndrome (MetS), activity of the fibrinolytic system is generally surmised to be decreased through increased plasminogen activator inhibitor-1 (PAI-1) generation. However, there have been no detailed reports describing whether the clot lysis activity is more dominant than increased clot formation activity for production of the thrombotic state in MetS.Methods
The global thrombosis test (GTT) is a novel method designed to test both clot formation and clot lysis activities under physiological conditions by using non-anticoagulated blood samples in vitro. We used the GTT to examine the thrombotic or thrombolytic states in males with MetS.Results
Lysis time, which reflects spontaneous clot lysis activity, was significantly longer in MetS subjects (median, 1494 s; range, 865-3596 s; n = 30) than in control subjects (median 1246 s; range, 667-2239 s; n = 53). There was no significant difference between the two groups in occlusion time, which reflects platelet function. The mean level of PAI-1 was significantly higher in MetS subjects than in controls (mean ± SE, 8.7 ± 1.1 and 5.0 ± 0.5 ng/mL, respectively). PAI-1 level and lysis time were significantly correlated (r = 0.400, P < 0.01).Conclusion
These results suggest that male patients with MetS are more likely than controls to experience a thrombotic state through decreased fibrinolytic activity due to increased PAI-1 generation, and that the GTT is useful for evaluating fibrinolytic activity in vitro. 相似文献10.
Diwadkar VA Goradia D Hosanagar A Mermon D Montrose DM Birmaher B Axelson D Rajarathinem R Haddad L Amirsadri A Zajac-Benitez C Rajan U Keshavan MS 《Progress in neuro-psychopharmacology & biological psychiatry》2011,35(5):1349-1354
Background
Working memory deficits abound in schizophrenia and attention deficits have been documented in schizophrenia and bipolar disorder. Adolescent offspring of patients may inherit vulnerabilities in brain circuits that subserve these cognitive domains. Here we assess impairments in offspring of schizophrenia (SCZ-Offspring) or bipolar (BP-Offspring) patients compared to controls (HC) with no family history of mood or psychotic disorders to the second degree.Methods
Three groups (n = 100 subjects; range: 10-20 yrs) of HC, SCZ-Offspring and BP-Offspring gave informed consent. Working memory was assessed using a delayed spatial memory paradigm with two levels of delay (2 s & 12 s); sustained attention processing was assessed using the Continuous Performance Task—Identical Pairs version.Results
SCZ-Offspring (but not BP-Offspring) showed impairments in working memory (relative to HC) at the longer memory delay indicating a unique deficit. Both groups showed reduced sensitivity during attention but only BP-Offspring significantly differed from controls.Conclusions
These results suggest unique (working memory/dorsal frontal cortex) and potentially overlapping (attention/fronto-striatal cortex) vulnerability pathways in adolescent offspring of patients with schizophrenia and bipolar disorder. Working memory and attention assessments in these offspring may assist in the clinical characterization of the adolescents vulnerable to SCZ or BP. 相似文献11.
Background
Right heart dysfunction is a crucial factor in risk stratification of normotensive patients with pulmonary embolism. Apart from biomarkers, determinants of right heart dysfunction in this group of patients are not yet well established.Aim and method
In order to identify such determinants, we analysed data of 252 patients with acute pulmonary embolism admitted to our hospital in 2008.Results
69 out of 140 patients showed right heart dysfunction by echocardiography within 24 hours after diagnosis, 71 did not. Right ventricular dysfunction was significantly more frequent in patients with central clots on computed tomography (p = 0.004), a history of syncope (p < 0.001) and among women on oral contraceptives (p = 0.003). In multiple regression analysis, only central thromboembolism (p < 0.001) was identified as individual predictor of right ventricular dysfunction. Age, gender, body mass index, idiopathic or recurrent thromboembolism, duration of symptoms, preceding surgery, room air oxygen saturation, carcinoma, hypertension, diabetes, renal disease, congestive left heart failure and concomitant lung disease were equally distributed. In comparison with NT-pro brain natriuretic peptide (PPV 67%, NPV 75%, p = 0.782) and troponin I (PPV 76%, NPV 62%, p = 0.336), central thromboembolism has shown to have a greater statistical power in predicting right heart dysfunction in normotensive patients with pulmonary embolism (PPV 78%, NPV 88%, p < 0.001).Conclusion
Among normotensive patients with acute pulmonary embolism, those with central clots seem to be at greater risk for echocardiographically evaluated right ventricular dysfunction. 相似文献12.
Caroline Dubertret Claire Bardel Nicolas Ramoz Pierre-Marie Martin Jean-Charles Deybach Jean Adès Philip Gorwood Laurent Gouya 《Progress in neuro-psychopharmacology & biological psychiatry》2010
Background
The gene coding for the D2 dopamine receptor (DRD2) is considered to be one of the most pertinent candidate genes in schizophrenia. However, genetic studies have yielded conflicting results whereas the promising TaqIA variant/rs1800497 has been mapped in a novel gene, ANKK1.Methods
We investigated eleven single nucleotide polymorphisms (SNPs) spanning the DRD2 and ANKK1 genes, using both a case–control association study comparing 144 independent patients to 142 matched healthy subjects, and a transmission disequilibrium test in 108 trios. This classical genetic study was coupled with a cladistic phylogeny-based association test of human variants, and with an interspecies evolution study of ANKK1.Results
Case–control study, followed by a 108 trios family-based association analysis for replication, revealed an association between schizophrenia and the ANKK1 rs1800497 (p = 0.01, Odds Ratio = 1.5, 95% Confidence Interval = 1.1–2.2), and the intergenic rs2242592 (p = 2 · 10− 4, OR = 1.8, 95%CI = 1.3–2.5). A significant SNP–SNP interaction was also found (p < 10− 5, OR = 2.0, 95%CI = 1.6–2.5). The phylogeny-based association test also identified an association between both these polymorphisms and schizophrenia. Finally, interspecies comparison of the sequences from chimpanzee, orangutan, rhesus macaque and human species suggested specific involvement of ANKK1 in the human lineage.Conclusions
Intergenic rs2242592 appears to be involved in the genetic vulnerability to schizophrenia, whereas the ANKK1 rs1800497 appears to have a modifying rather than causative effect. Finally, ANKK1 may be a specific human lineage-trait involved in a specific human disease, schizophrenia. 相似文献13.
Sasayama D Hori H Teraishi T Hattori K Ota M Tatsumi M Higuchi T Amano N Kunugi H 《Progress in neuro-psychopharmacology & biological psychiatry》2012,38(2):341-344
Background
The β3-adrenoceptor (ADRB3) gene Trp64Arg polymorphism has been shown to be associated with obesity as well as type 2 diabetes and cardiovascular disease. The incidence of overweight and the risks of type 2 diabetes and cardiovascular disease are also increased in major depression and schizophrenia. We hypothesized that the Trp64Arg polymorphism may be associated with increased risk of schizophrenia and depression.Methods
The Trp64Arg was genotyped in 504 patients with schizophrenia, 650 with major depressive disorder (MDD), and 1170 healthy controls. Of these participants, body mass index (BMI) data were available for 125 patients with schizophrenia, 219 with MDD, and 261 controls.Results
No significant difference in genotype or allele distribution was found across the diagnostic groups. No significant difference in BMI was observed between the Arg allele carriers and the non-carriers in the MDD and the control groups. However, patients with schizophrenia carrying the Arg allele had significantly higher BMI (Mean (SD): Arg carriers: 26.5 (6.9), Arg non-carriers: 23.8 (4.3); P = 0.019) and a higher rate of being overweight (BMI of 25 or more) compared to their counterparts (Trp/Trp group) (% overweight (SE): Arg carriers: 52.3 (7.5), Arg non-carriers: 32.1 (5.2); P = 0.027).Conclusions
We obtained no evidence for the association of ADRB3 Trp64Arg with the development of MDD or schizophrenia. However, the Arg allele was found to be associated with higher BMI and being overweight in patients with schizophrenia. This may imply that genotyping ADRB3 is of clinical use to detect schizophrenic individuals at risk for developing obesity. 相似文献14.
Campbell EC DeJesus M Herman BK Cuffel BJ Sanders KN Dodge W Dhopesh V Caroff SN 《Progress in neuro-psychopharmacology & biological psychiatry》2011,35(1):246-251
Background
Evidence on antipsychotic prescribing decisions is limited. This pilot study quantified factors considered in choosing an antipsychotic and evaluated the influence of metabolic status on treatment decisions.Methods
Prescribing decisions by 4 psychiatrists were examined based on 80 adult patients initiated on antipsychotic medication diagnosed with schizophrenia, schizoaffective disorder or bipolar disorder by DSM-IV criteria, who were admitted to an acute inpatient psychiatric program of an urban Veterans Affairs Medical Center. The primary analysis examined the association between antipsychotic treatment choice and predictions of symptom control and metabolic risk. Secondary analyses included comparison of the chosen and next best treatments in predicted symptom control and metabolic risk, the frequency of reasons cited for drug choice, and the association between treatment choice and patients' baseline metabolic parameters. Mean differences and odds-ratios (OR) with 95% confidence intervals were used to compare relationships between treatment choice, ratings of risk and metabolic data.Results
Antipsychotic choice correlated significantly with ratings of predicted symptom control (OR = .92, p = 0.02) and metabolic risk (OR = .88, p = 0.01). Mean differences between the chosen and next best drugs were significant but small in predicted symptom control (F = 2.81, df = 3, 76; p < 0.05) compared with larger differences in anticipated metabolic risk (F = 14.80, df = 3, 76; p = 0.0001). Nevertheless, among 24 identified reasons influencing drug selection, anticipated metabolic risk of chosen antipsychotics was cited less often than efficacy measures. In contrast to psychiatrists' expectations of metabolic risk with selected treatments, we found that patients' actual baseline BMI, fasting glucose, blood pressure, and Framingham risk levels did not necessarily predict antipsychotic treatment choice independent of other factors.Conclusion
In the context of an acute psychiatric hospitalization, pilot data suggest that predictions of symptom control and metabolic risk correlated significantly with antipsychotic choice, but study psychiatrists were willing to assume relative degrees of metabolic risk in favor of effective symptom control. However, prescribing decisions were influenced by numerous patient and treatment factors. These findings support the potential utility of the ATCQ questionnaire in quantifying antipsychotic prescribing decisions. Further validation studies of the ATCQ questionnaire could enhance translation of research findings and application of treatment guidelines. 相似文献15.
Introduction
To test the hypothesis that the platelet microparticle (PMP) and endothelial microparticle (EMP) may contribute to the hypercoagulability associated with microvascular thrombosis in patients with nontraumatc osteonecrosis of the femoral head (ONFH).Materials and methods
The study comprised 46 patients who had been diagnosed with ONFH and 20 control subjects. The plasma was ultracentrifuged, and then PMPs and EMPs were examined by the flow cytometry. The thrombotic and fibrinolytic disorders were investigated.Results
The numbers of PMPs expressing P-selectin and CD42a and EMPs expressing E-selectin and CD31 in the ONFH patients were significantly higher than those in the controls (P < 0.001). The number of MPs was correlated with the level of the serum C-reactive protein (CRP) (r = 0.661, P < 0.001), but there was a poor correlation between the MPs counts and the risk factors for ONFH (P > 0.05). The mean levels PAI-1, F1 + 2, and TAT were higher in the patients with ONFH than in the controls (P < 0.05).Conclusions
The elevated numbers of PMPs and EMPs may contribute to hypercoagulability in the ONFH patients. This may provide important pathophysiological insights into the hypercoagulability associated with nontraumatic ONFH and have implications for pharmacological prevention and treatment of ONFH. 相似文献16.
Igue R Potvin S Bah R Stip E Bouchard RH Lipp O Gendron A Kouassi E 《Progress in neuro-psychopharmacology & biological psychiatry》2011,35(7):1695-1698
Background
Some but not all antipsychotics have been shown to modulate plasma cytokine levels in schizophrenia patients. Thus far, the most consistent finding has been the increase in plasma levels of soluble interleukin (IL)-2 receptor (sIL-2R) associated with clozapine treatment. Quetiapine is a second-generation antipsychotic with a pharmacological profile similar to that of clozapine, but its immunomodulatory effects have not been investigated in schizophrenia yet. The purpose of this exploratory study was to examine the changes in plasma levels of sIL-2R in schizophrenia during quetiapine treatment and association with psychopathology.Methods
Participants were 29 schizophrenia-spectrum disorder patients (DSM-IV criteria), and 28 healthy controls. Patients had a comorbid substance use disorder (cannabis > alcohol > cocaine), since quetiapine is increasingly used in this population of dual diagnosis. No participant suffered from infection or overt inflammatory diseases. On baseline, patients taking mostly second-generation antipsychotics were switched to quetiapine for a 12-week open-label trial. Five patients were drop-outs. Mean dose of quetiapine for trial completers (n = 24) was 466.6 mg ± 227.3. Psychiatric variables were evaluated with the Positive and Negative Syndrome Scale and the Calgary Depression Scale for Schizophrenia. Plasma sIL-2R levels were assessed at baseline, weeks 6 and 12 in patients, and in healthy controls, using sandwich immunoassay. Plasma IL-6 and IL-1 receptor antagonist (IL-1RA) were measured for comparison purposes.Results
On baseline, plasma sIL-2R, IL-6 and IL-1RA levels were higher in dual-diagnosis patients, compared to controls. Plasma sIL-2R further increased after quetiapine treatment (p = 0.037), while plasma IL-6 and IL-1RA did not change. Clinical improvements were observed in positive, negative and depressive symptoms, and substance abuse severity (all p < 0.01). Interestingly, changes in sIL-2R levels during treatment were inversely correlated with changes in positive symptoms (r = − 0.524; p = 0.009). That is, increases in sIL-2R levels were associated with reductions in positive symptoms.Conclusion
These data show that quetiapine elevates, like clozapine, sIL-2R levels in schizophrenia. Furthermore, the results suggest that sIL-2R alterations in schizophrenia rely on complex interplays between antipsychotics and the positive symptoms of the disorder. Future randomized controlled trials involving larger samples of schizophrenia patients are warranted to determine whether changes in plasma sIL-2R are quetiapine-related. 相似文献17.
Shin Ogino Seiya MiyamotoTomomi Tenjin Rei KitajimaKazuaki Ojima Nobumi Miyake Yasuyuki FunamotoJun Arai Sachiko TsukaharaYukie Ito Masanori TadokoroKiriko Anai Shinobu TatsunamiHiroshi Kubota Yasuhiro KanedaNoboru Yamaguchi 《Progress in neuro-psychopharmacology & biological psychiatry》2011,35(1):78-83
Background
The high use of long-term antiparkinsonian anticholinergic drugs with antipsychotics has been identified as an important issue in the treatment of schizophrenia in Japan. The aim of this study was to evaluate the effects of gradual discontinuation of biperiden, an anticholinergic drug, on cognitive function and quality of life (QOL) in schizophrenia.Methods
Thirty-four schizophrenic patients who had received a second-generation antipsychotic (SGA) with concomitant biperiden for at least 3 months were enrolled. Before and 4 weeks after discontinuation of biperiden, the Japanese version of the Brief Assessment of Cognition in Schizophrenia (BACS-J) and the Schizophrenia Quality of Life Scale (SQLS-J) were administered. Clinical evaluation also included the Positive and Negative Syndrome Scale (PANSS). To compare the practice effect on BACS-J, 10 chronic patients with schizophrenia were assessed without tapering biperiden.Results
Biperiden was discontinued safely in most patients, and no emergent extrapyramidal symptoms were observed. Significant improvements were shown in attention, processing speed, and composite score, as measured by the BACS-J without practice effect. In addition, the psychosocial condition score on the SQLS-J and the general psychopathology score on the PANSS significantly improved after biperiden discontinuation.Conclusion
Discontinuation of long-term biperiden use may be warranted in patients with schizophrenia treated with SGAs, as it may improve cognitive function, subjective QOL, and psychiatric symptoms with no significant adverse effects. 相似文献18.
Lázaro L Castro-Fornieles J Cullell C Andrés S Falcón C Calvo R Bargalló N 《Progress in neuro-psychopharmacology & biological psychiatry》2011,35(8):1863-1869
Background
The aim of this study was to determine whether treated stabilized adolescents with obsessive-compulsive disorder (OCD) present brain structure differences in comparison with healthy control subjects.Methods
Twenty-seven adolescents with already-treated OCD and 27 healthy controls matched by age, sex and estimated intellectual level were assessed by means of psychopathological scales and magnetic resonance imaging (MRI). Axial three-dimensional T1-weighted images were obtained in a 1.5 T scanner and analyzed using optimized voxel-based morphometry (VBM).Results
Compared with controls, stabilized patients with OCD did not present any statistical differences in the whole brain. However, a small volume correction analysis yielded significant results that survived correction for multiple comparisons, showing decreased white matter (WM) volume in a small area of the parietal cortex (t = 3.39, p = 0.045 FWE (family wise error)-corrected) of OCD patients in comparison with healthy controls. There was no significant correlation between decreased WM volume in the parietal cortex and obsessive-compulsive symptomatology.Conclusion
There were no global significant differences in either gray matter (GM) or WM. Small differences were found between adolescent patients with stabilized OCD and healthy controls as regards in WM volume in right parietal areas. The parietal lobe may play a role in the pathophysiology of OCD, even in clinically stabilized patients. 相似文献19.
Shengxia Fang 《Thrombosis research》2010,125(5):e197
Introduction
The C242T polymorphism of p22phox gene (rs4673) has been linked to the reduced coronary artery disease (CAD) risk, but results in the published literatures are controversial. A meta-analysis was performed to assess the effect of this polymorphism on the CAD risk.Methods
A comprehensive search was conducted to identify all studies on the association of p22phox gene C242T polymorphism with CAD risk. The fixed or random effect pooled measure was selected based on the homogeneity test among studies. Heterogeneity among studies was evaluated using Q test and the I2 of Higgins and Thompson. Meta-regression was used to explore the sources of between-study heterogeneity. Publication bias was estimated using modified Egger's linear regression test proposed by Harbord etal.Results
We identified 15 published articles including 6273 CAD cases and 5045 controls. In this studied overall and non-Asian populations, we didn't found any significant association of p22phox gene C242T polymorphism with CAD in any of codominant, dominant, and recessive models. Only in Asian population, both fixed effect model (FEM) and random effect model (REM) indicated the significant protective effect both in codominant (FEM: OR = 0.771, 95%CI: 0.681-0.873; REM: OR = 0.751, 95%CI: 0.607-0.930) and dominant (FEM: OR = 0.714, 95%CI: 0.621-0.822; REM: OR = 0.694, 95%CI: 0.538-0.895) models with strong evidence for between-study heterogeneity (I2 = 52.6% for codominant and I2 = 56.5% for dominant), but not in recessive model. No evidence of publication bias was detected.Conclusions
The results suggested a significant heterogeneity across ethnicities about the relationship between the T allele of p22phox gene C242T polymorphism and reduced CAD risk, with a significant protective effect only in Asian population that needs to be confirmed by further studies. 相似文献20.
Nan Li 《Brain research bulletin》2010,81(1):38-42