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1.
Ying Wang Yigang Feng Yanbin Jia Yanping Xie Wensheng Wang Yufang Guan Shuming Zhong Dan Zhu Li Huang 《PloS one》2013,8(12)
Background
Whether schizophrenia and bipolar disorder are the clinical outcomes of discrete or shared causative processes is much debated in psychiatry. Several studies have demonstrated anomalous structural and functional superior temporal gyrus (STG) symmetries in schizophrenia. We examined bipolar patients to determine if they also have altered STG asymmetry.Methods
Whole-head magnetoencephalography (MEG) recordings of auditory evoked fields were obtained for 20 subjects with schizophrenia, 20 with bipolar disorder, and 20 control subjects. Neural generators of the M100 auditory response were modeled using a single equivalent current dipole for each hemisphere. The source location of the M100 response was used as a measure of functional STG asymmetry.Results
Control subjects showed the typical M100 asymmetrical pattern with more anterior sources in the right STG. In contrast, both schizophrenia and bipolar disorder patients displayed a symmetrical M100 source pattern. There was no significant difference in the M100 latency and strength in bilateral hemispheres within three groups.Conclusions
Our results indicate that disturbed asymmetry of temporal lobe function may reflect a common deviance present in schizophrenia and bipolar disorder, suggesting the two disorders might share etiological and pathophysiological factors. 相似文献2.
Background and Objectives
Mismatch negativity (MMN) is an event-related potential (ERP) measure of preattentional sensory processing. While deficits in the auditory MMN are robust electrophysiological findings in schizophrenia, little is known about visual mismatch response and its association with social cognitive functions such as emotion recognition in schizophrenia. Our aim was to study the potential deficit in the visual mismatch response to unexpected facial emotions in schizophrenia and its association with emotion recognition impairments, and to localize the sources of the mismatch signals.Experimental Design
The sample comprised 24 patients with schizophrenia and 24 healthy control subjects. Controls were matched individually to patients by gender, age, and education. ERPs were recorded using a high-density 128-channel BioSemi amplifier. Mismatch responses to happy and fearful faces were determined in 2 time windows over six regions of interest (ROIs). Emotion recognition performance and its association with the mismatch response were also investigated.Principal Observations
Mismatch signals to both emotional conditions were significantly attenuated in patients compared to controls in central and temporal ROIs. Controls recognized emotions significantly better than patients. The association between overall emotion recognition performance and mismatch response to the happy condition was significant in the 250–360 ms time window in the central ROI. The estimated sources of the mismatch responses for both emotional conditions were localized in frontal regions, where patients showed significantly lower activity.Conclusions
Impaired generation of mismatch signals indicate insufficient automatic processing of emotions in patients with schizophrenia, which correlates strongly with decreased emotion recognition. 相似文献3.
Muzaffer Kaser Fruzsina Soltesz Phil Lawrence Sam Miller Chris Dodds Rodney Croft Robert B. Dudas Rashid Zaman Emilio Fernandez-Egea Ulrich Müller Anna Dean Edward T. Bullmore Pradeep J. Nathan 《PloS one》2013,8(12)
Background
Impairments in mismatch negativity (MMN) generation have been consistently reported in patients with schizophrenia. However, underlying oscillatory activity of MMN deficits in schizophrenia and the relationship with cognitive impairments have not been investigated in detail. Time-frequency power and phase analyses can provide more detailed measures of brain dynamics of MMN deficits in schizophrenia.Method
21 patients with schizophrenia and 21 healthy controls were tested with a roving frequency paradigm to generate MMN. Time-frequency domain power and phase-locking (PL) analysis was performed on all trials using short-time Fourier transforms with Hanning window tapering. A comprehensive battery (CANTAB) was used to assess neurocognitive functioning.Results
Mean MMN amplitude was significantly lower in patients with schizophrenia (95% CI 0.18 - 0.77). Patients showed significantly lower EEG power (95% CI -1.02 - -0.014) in the ~4-7 Hz frequency range (theta band) between 170 and 210 ms. Patients with schizophrenia showed cognitive impairment in multiple domains of CANTAB. However, MMN impairments in amplitude and power were not correlated with clinical measures, medication dose, social functioning or neurocognitive performance.Conclusion
The findings from this study suggested that while MMN may be a useful marker to probe NMDA receptor mediated mechanisms and associated impairments in gain control and perceptual changes, it may not be a useful marker in association with clinical or cognitive changes. Trial-by-trial EEG power analysis can be used as a measure of brain dynamics underlying MMN deficits which also can have implications for the use of MMN as a biomarker for drug discovery. 相似文献4.
Jolanta Zanelli Kevin Morgan Paola Dazzan Craig Morgan Manuela Russo Izabela Pilecka Paul Fearon Arsime Demjaha Gill A. Doody Peter B. Jones Robin M. Murray Abraham Reichenberg 《PloS one》2013,8(10)
Background
Patients with schizophrenia and other psychoses exhibit a wide range of neuropsychological deficits. An unresolved question concerns whether there are gender differences in cognitive performance.Methods
Data were derived from a multi-centre population based case-control study of patients with first-episode psychosis. A neuropsychological test battery was administered to patients with a diagnosis of schizophrenia or schizoaffective disorder (N=70, 36% females), bipolar/mania (N=34, 60% females), depressive psychosis (N=36, 58% females) and healthy controls (N=148, 55% females). Generalized and specific cognitive deficits were compared.Results
There was strong evidence for disorder-specific gender differences in neuropsychological performance. Males and females with schizophrenia showed similar pervasive neuropsychological impairments. In psychotic depressive disorder females performed worse than males across neuropsychological measures. Differences in neuropsychological performance between males and females with bipolar/manic disorder were restricted to language functions. Symptom severity did not contribute to the observed gender differences.Conclusions
Early in the course of psychotic illness, gender related factors appear to moderate the severity of cognitive deficits in depressive psychosis and bipolar/mania patients. 相似文献5.
6.
Background
Theoretically semantic processing can be separated into early automatic semantic activation and late contextualization. Semantic processing deficits have been suggested in patients with schizophrenia, however it is not clear which stage of semantic processing is impaired. We attempted to clarify this issue by conducting a meta-analysis of the N400 component.Methods
Twenty-one studies met the inclusion criteria for the meta-analysis procedure. The Comprehensive Meta-Analysis software package was used to compute pooled effect sizes and homogeneity.Results
Studies favoring early automatic activation produced a significant effect size of −0.41 for the N400 effect. Studies favoring late contextualization generated a significant effect size of −0.36 for the N400 effect, a significant effect size of −0.52 for N400 for congruent/related target words, and a significant effect size of 0.82 for the N400 peak latency.Conclusion
These findings suggest the automatic spreading activation process in patients with schizophrenia is very similar for closely related concepts and weakly or remotely related concepts, while late contextualization may be associated with impairments in processing semantically congruent context accompanied by slow processing speed. 相似文献7.
Pascal Auquier Aurelie Tinland Cecile Fortanier Anderson Loundou Karine Baumstarck Christophe Lancon Laurent Boyer 《PloS one》2013,8(10)
Objective
To provide new evidence regarding the suitability of using quality of life (QoL) measurements in homeless people with schizophrenia, we assess the acceptability and psychometric properties of a specific QoL instrument (S-QoL 18) in a population of homeless people with schizophrenia, and we compare their QoL levels with those observed in non-homeless people with schizophrenia.Methods
This multi-centre prospective study was conducted in the following 4 French cities: Lille, Marseille, Paris and Toulouse. Two hundred and thirty-six homeless patients with schizophrenia were recruited over a 12 month-period. The S-QoL 18 was tested for construct validity, reliability, external validity and sensitivity to change. The QoL of the 236 homeless patients was compared with 236 French age- and sex-matched non-homeless patients with schizophrenia.Results
The eight-factor structure of the S-QoL 18 was confirmed by confirmatory factor analysis (RMSEA = 0.035, CFI = 0.95, GFI = 0.99 and SRMR = 0.015). Internal consistency, reliability and sensitivity to change were satisfactory. External validity was confirmed via correlations between S-QoL 18 dimension scores and SF-36, symptomatology and recovery scores. The percentage of missing data did not exceed 5%. Finally, homeless patients had significantly lower QoL levels than non-homeless patients with schizophrenia.Conclusions
These results demonstrate the satisfactory acceptability and psychometric properties of the S-QoL 18, suggesting the validity of QoL measurement among homeless patients with schizophrenia. Our study also reported that QoL levels in homeless patients with schizophrenia were dramatically low, highlighting the need for new policies to eradicate homelessness and tackle poverty. 相似文献8.
Kim H. W. Verweij Eske M. Derks Genetic Risk Outcome in Psychosis investigators 《PloS one》2013,8(10)
Background
The degree of intellectual impairment in schizophrenia patients and their relatives has been suggested to be associated with the degree of familial loading for schizophrenia. Since other psychiatric disorders are also more present in relatives of schizophrenia patients, the definition of family history should be broadened. The association between family history for psychiatric disorder and intelligence scores was investigated in patients with non-affective psychosis, their unaffected siblings and controls.Methods
A sample of 712 schizophrenia proband families (696 patients and 766 siblings) and 427 healthy control families (517 subjects) participated in this study. Family history of psychiatric disorder was determined while excluding the data of the participating schizophrenia patient. A dichotomous division was made between families with no first- or second degree relative with psychiatric disorder and families with one or more affected relatives. Total intelligence scores were estimated by admission of the short form of the Wechsler Adult Intelligence Scale III.Results
A significant interaction was found between family history of psychiatric disorder and clinical status (F(2,1086.87)= 4.17; p=.016). Patients with a positive family history of psychiatric disorder obtained higher intelligence scores compared to patients with no family history (mean IQ scores are 95.52 and 92.72) with an opposite effect in controls (mean IQ scores are 108.71 and 111.19). No significant difference was found between siblings of schizophrenia patients with or without a positive family history (mean IQ scores are 102.98 and 103.24).Conclusion
In patients with schizophrenia, a negative family history of psychiatric disorder was associated with relatively low IQ suggesting that the etiology in these patients may involve environmental or genetic factors which are unique to the patient and are not observed in other relatives. Possible factors include severe environmental stressors containing premature birth or brain injury and genetic factors (e.g de novo Copy Number Variants). 相似文献9.
Jordan M. Ramsey Emanuel Schwarz Paul C. Guest Nico J. M. van Beveren F. Markus Leweke Matthias Rothermundt Bernhard Bogerts Johann Steiner Sabine Bahn 《PloS one》2013,8(11)
Background
In schizophrenia, sex specific dimorphisms related to age of onset, course of illness and response to antipsychotic treatment may be mirrored by sex-related differences in the underlying molecular pathways.Methodology/Principal Findings
Here, we have carried out multiplex immunoassay profiling of sera from 4 independent cohorts of first episode antipsychotic naive schizophrenia patients (n = 133) and controls (n = 133) to identify such sex-specific illness processes in the periphery. The concentrations of 16 molecules associated with hormonal, inflammation and growth factor pathways showed significant sex differences in schizophrenia patients compared with controls. In female patients, the inflammation-related analytes alpha-1-antitrypsin, B lymphocyte chemoattractant BLC and interleukin-15 showed negative associations with positive and negative syndrome scale (PANSS) scores. In male patients, the hormones prolactin and testosterone were negatively associated with PANSS ratings. In addition, we investigated molecular changes in a subset of 33 patients before and after 6 weeks of treatment with antipsychotics and found that treatment induced sex-specific changes in the levels of testosterone, serum glutamic oxaloacetic transaminase, follicle stimulating hormone, interleukin-13 and macrophage-derived chemokine. Finally, we evaluated overlapping and distinct biomarkers in the sex-specific molecular signatures in schizophrenia, major depressive disorder and bipolar disorder.Conclusions/Significance
We propose that future studies should investigate the common and sex-specific aetiologies of schizophrenia, as the current findings suggest that different therapeutic strategies may be required for male and female patients. 相似文献10.
Background
During HCV infection, the activation status of peripheral blood monocytes and its impact on HCV replication are poorly understood. We hypothesized that a modified activation of peripheral blood monocytes in HIV-HCV coinfected compared to HCV monoinfected patients may contribute to different monocytes reservoirs of HCV replication.Methods
We performed a case-control analysis involving HCV-infected patients with and without HIV coinfection. In peripheral blood mononuclear cells (PBMCs), peripheral blood lymphocytes (PBLs) and peripheral blood monocytes isolated from HCV monoinfected and HIV-HCV coinfected patients, intracellular HCV load and a marker of cellular activation, nuclear factor-kappaB (NF-κB) activation, were quantified using intracellular detection of HCV-core protein and electrophoretic mobility shift assay, respectively.Results
Intracellular HCV loads were higher in monocytes isolated from HIV-HCV coinfected patients than in those of monoinfected patients. Among PBMCs isolated from HIV-HCV coinfected patients, intracellular HCV loads were higher in monocytes compared to PBLs. Cellular activation as measured by NF-κB activation was higher in monocytes isolated from HIV-HCV coinfected patients than in those of monoinfected patients.Conclusions
Our results reveal the peripheral blood monocytes as an important extrahepatic reservoir for HCV in HIV-HCV coinfected patients and indicate a potential association between the activation state of monocytes and the size of the HCV reservoir in HIV-HCV coinfected patients. 相似文献11.
Background
The functional polymorphism Val158Met in the catechol-O-methyltransferase (COMT) gene has been associated with differences in prefrontal cognitive functions in patients with schizophrenia and healthy individuals. Several studies have indicated that the Met allele is associated with better performance on measures of cognitive function. We investigated whether the COMT Val158Met genotype was associated with cognitive function in 149 healthy controls and 118 patients with schizophrenia.Methods
Cognitive function, including verbal memory, working memory, motor speed, attention, executive function and verbal fluency, was assessed by the Brief Assessment of Cognition in Schizophrenia (BACS-J). We employed a one-way analysis of variance (ANOVA) and a multiple regression analysis to determine the associations between the COMT Val158Met genotype and the BACS-J measurements.Results
The one-way ANOVA revealed a significant difference in the scores on the Tower of London, a measure of executive function, between the different Val158Met genotypes in the healthy controls (p = 0.023), and a post-hoc analysis showed significant differences between the scores on the Tower of London in the val/val genotype group (18.6 ± 2.4) compared to the other two groups (17.6 ± 2.7 for val/met and 17.1 ± 3.2 for met/met; p = 0.027 and p = 0.024, respectively). Multiple regression analyses revealed that executive function was significantly correlated with the Val158Met genotype (p = 0.003). However, no evidence was found for an effect of the COMT on any cognitive domains of the BACS-J in the patients with schizophrenia.Conclusion
These data support the hypothesis that the COMT Val158Met genotype maintains an optimal level of dopamine activity. Further studies should be performed that include a larger sample size and include patients on and off medication, as these patients would help to confirm our findings. 相似文献12.
Michael Eriksen Benros Thomas Munk Laursen Susanne Oksbjerg Dalton Merete Nordentoft Preben Bo Mortensen 《PloS one》2013,8(11)
Background
Maternal immune responses and brain-reactive antibodies have been proposed as possible causal mechanisms for schizophrenia and some child psychiatric disorders. According to this hypothesis maternal antibodies may cross the placenta and interact with the developing CNS of the fetus causing future neurodevelopmental disorders. Therefore, we investigated if children of mothers with cancer might be at higher risk of developing psychiatric disorders, with particular focus on small-cell lung cancer, which is known to induce production of antibodies binding to CNS elements.Methods
Nationwide population-based registers were linked, including the Danish Psychiatric Central Register and The Danish Cancer Registry. Data were analyzed as a cohort study using survival analysis techniques. Incidence rate ratios (IRRs) and accompanying 95% confidence intervals (CIs) were used as measures of relative risk.Results
In general, parental cancer was not associated with schizophrenia in the offspring (IRR, 0.98; 95% CI, 0.95-1.01). Furthermore, we found no temporal associations with maternal cancer in general; neither around the pregnancy period. However, maternal small-cell lung cancer increased the risk of early-onset schizophrenia and maternal small-cell lung cancer diagnosed within 20 years after childbirth increased the risk of schizophrenia. Parental cancer was not associated with child psychiatric disorders (IRR, 1.01; 95% CI, 0.98-1.05) except for the smoking related cancers. There was a significantly increased risk of child psychiatric disorders in offspring of both mothers (IRR, 1.35; 95% CI, 1.16-1.58) and fathers (IRR, 1.47; 95% CI, 1.30-1.66) with lung cancer of all types.Conclusions
In general, parental cancer did not increase the risk of schizophrenia nor of child psychiatric disorders. However, maternal small-cell lung cancer increased the risk of schizophrenia in subgroups; and lung cancer in general increased the risk of child psychiatric disorders, which could be due to risk factors associated with parental smoking. 相似文献13.
Jean Yves Le Reste Patrice Nabbe Charles Rivet Charilaos Lygidakis Christa Doerr Slawomir Czachowski Heidrun Lingner Stella Argyriadou Djurdjica Lazic Radost Assenova Melida Hasaganic Miquel Angel Munoz Hans Thulesius Bernard Le Floch Jeremy Derriennic Agnieska Sowinska Harm Van Marwijk Claire Lietard Paul Van Royen 《PloS one》2015,10(1)
Background
Multimorbidity, according to the World Health Organization, exists when there are two or more chronic conditions in one patient. This definition seems inaccurate for the holistic approach to Family Medicine (FM) and long-term care. To avoid this pitfall the European General Practitioners Research Network (EGPRN) designed a comprehensive definition of multimorbidity using a systematic literature review.Objective
To translate that English definition into European languages and to validate the semantic, conceptual and cultural homogeneity of the translations for further research.Method
Forward translation of the EGPRN’s definition of multimorbidity followed by a Delphi consensus procedure assessment, a backward translation and a cultural check with all teams to ensure the homogeneity of the translations in their national context. Consensus was defined as 70% of the scores being higher than 6. Delphi rounds were repeated in each country until a consensus was reachedResults
229 European medical expert FPs participated in the study. Ten consensual translations of the EGPRN comprehensive definition of multimorbidity were achieved.Conclusion
A comprehensive definition of multimorbidity is now available in English and ten European languages for further collaborative research in FM and long-term care. 相似文献14.
Blanca Ortega-Roldán Sonia Rodríguez-Ruiz Pandelis Perakakis M. Carmen Fernández-Santaella Jaime Vila 《PloS one》2014,9(7)
Background
Body dissatisfaction is the most relevant body image disturbance in bulimia nervosa (BN). Research has shown that viewing one''s own body evokes negative thoughts and emotions in individuals with BN. However, the psychophysiological mechanisms involved in this negative reaction have not yet been clearly established. Our aim was to examine the emotional and attentional processes that are activated when patients with BN view their own bodies.Method
We examined the effects of viewing a video of one''s own body on the physiological (eye-blink startle, cardiac defense, and skin conductance) and subjective (pleasure, arousal, and control ratings) responses elicited by a burst of 110 dB white noise of 500 ms duration. The participants were 30 women with BN and 30 healthy control women. The experimental task consisted of two consecutive and counterbalanced presentations of the auditory stimulus preceded, alternatively, by a video of the participant''s own body versus no such video.Results
The results showed that, when viewing their own bodies, women with BN experienced (a) greater inhibition of the startle reflex, (b) greater cardiac acceleration in the first component of the defense reaction, (c) greater skin conductance response, and (d) less subjective pleasure and control combined with greater arousal, compared with the control participants.Conclusion
Our findings suggest that, for women with BN, peripheral-physiological responses to self-images are dominated by attentional processes, which provoke an immobility reaction caused by a dysfunctional negative response to their own body. 相似文献15.
Sarah Hardoon Joseph F Hayes Ruth Blackburn Irene Petersen Kate Walters Irwin Nazareth David P. J. Osborn 《PloS one》2013,8(12)
Background
There is increasing emphasis on primary care services for individuals with severe mental illnesses (SMI), including schizophrenia, bipolar disorder, and other non-organic psychotic disorders. However we lack information on how many people receive these different diagnoses in primary care. Primary care databases offer an opportunity to explore the recording of new SMI diagnoses in representative general practices.Methods
We used data from The UK Health Improvement Network (THIN) primary care database including longitudinal patient records for individuals aged over 16 years from 437 general practices. We determined the annual GP recorded rate of first diagnosis of SMI by age, gender, social deprivation and urbanicity between 2000 and 2010.Results
We identified 10,520 individuals with a first record of schizophrenia, bipolar disorder or other non-organic psychosis among 4,164,794 patients. This corresponded to a rate of first diagnosis of 46.4 per 100,000 person years at risk (PYAR) (95% CI 45.4 to 47.4) in the 16–65 age group. The rate of first record of schizophrenia was 9.2 per 100,000 PYAR (95% CI 8.7 to 9.6) in this age group, bipolar disorder was 15.0 per 100,000 PYAR (95% CI 14.4 to 15.5) and other non-organic psychotic disorder was 22.3 per 100,000 PYAR (95% CI 21.6 to 23.0).Conclusions
The rates of GP recorded SMI in primary care records were broadly comparable to incidence rates from previous epidemiological studies of SMI and show similar patterns by socio-demographic characteristics. However there were some differences by specific diagnoses. GPs may be recording rates that are higher than those used to commission services. 相似文献16.
Caio Cesar de Souza Alves Adam Collison Luke Hatchwell Maximilian Plank Matthew Morten Paul S. Foster Sebastian L. Johnston Cristiane Fran?a da Costa Mauro Vieira de Almeida Henrique Couto Teixeira Ana Paula Ferreira Joerg Mattes 《PloS one》2013,8(11)
Background
Severe asthma is associated with T helper (TH) 2 and 17 cell activation, airway neutrophilia and phosphoinositide-3-kinase (PI3K) activation. Asthma exacerbations are commonly caused by rhinovirus (RV) and also associated with PI3K-driven inflammation. Anthraquinone derivatives have been shown to reduce PI3K-mediated AKT phosphorylation in-vitro.Objective
To determine the anti-inflammatory potential of anthraquinones in-vivo.Methods
BALB/c mice were sensitized and challenged with crude house dust mite extract to induce allergic airways disease and treated with mitoxantrone and a novel non-cytotoxic anthraquinone derivative. Allergic mice were also infected with RV1B to induce an exacerbation.Results
Anthraquinone treatment reduced AKT phosphorylation, hypoxia-inducible factor-1α and vascular endothelial growth factor expression, and ameliorated allergen- and RV-induced airways hyprereactivity, neutrophilic and eosinophilic inflammation, cytokine/chemokine expression, mucus hypersecretion, and expression of TH2 proteins in the airways. Anthraquinones also boosted type 1 interferon responses and limited RV replication in the lung.Conclusion
Non-cytotoxic anthraquinone derivatives may be of therapeutic benefit for the treatment of severe and RV-induced asthma by blocking pro-inflammatory pathways regulated by PI3K/AKT. 相似文献17.
Nicholas T. Funderburg Adriana Andrade Ellen S. Chan Susan L. Rosenkranz Darlene Lu Brian Clagett Heather A. Pilch-Cooper Benigno Rodriguez Judith Feinberg Eric Daar John Mellors Daniel Kuritzkes Jeffrey M. Jacobson Michael M. Lederman 《PloS one》2013,8(12)
Background
The dynamics of CD4+ T cell reconstitution and changes in immune activation and inflammation in HIV-1 disease following initiation of antiretroviral therapy (ART) are incompletely defined and their underlying mechanisms poorly understood.Methods
Thirty-nine treatment-naïve patients were treated with raltegravir, tenofovir DF and emtricitabine. Immunologic and inflammatory indices were examined in persons with sustained virologic control during 48 weeks of therapy.Results
Initiation of ART increased CD4+ T cell numbers and decreased activation and cell cycle entry among CD4+ and CD8+ T cell subsets, and attenuated markers of coagulation (D-dimer levels) and inflammation (IL-6 and TNFr1). These indices decayed at different rates and almost all remained elevated above levels measured in HIV-seronegatives through 48 weeks of viral control. Greater first and second phase CD4+ T cell restoration was related to lower T cell activation and cell cycling at baseline, to their decay with treatment, and to baseline levels of selected inflammatory indices, but less so to their changes on therapy.Conclusions
ART initiation results in dynamic changes in viral replication, T cell restoration, and indices of immune activation, inflammation, and coagulation. These findings suggest that determinants of T cell activation/cycling and inflammation/coagulation may have distinguishable impact on immune homeostasis.Trial Registration
Clinicaltrials.gov NCT00660972 相似文献18.
Qi Li Charlton Cheung Ran Wei Edward S. Hui Joram Feldon Urs Meyer Sookja Chung Siew E. Chua Pak C. Sham Ed X. Wu Grainne M. McAlonan 《PloS one》2009,4(7)
Objectives
Maternal infection during pregnancy increases risk of severe neuropsychiatric disorders, including schizophrenia and autism, in the offspring. The most consistent brain structural abnormality in patients with schizophrenia is enlarged lateral ventricles. However, it is unknown whether the aetiology of ventriculomegaly in schizophrenia involves prenatal infectious processes. The present experiments tested the hypothesis that there is a causal relationship between prenatal immune challenge and emergence of ventricular abnormalities relevant to schizophrenia in adulthood.Method
We used an established mouse model of maternal immune activation (MIA) by the viral mimic PolyI:C administered in early (day 9) or late (day 17) gestation. Automated voxel-based morphometry mapped cerebrospinal fluid across the whole brain of adult offspring and the results were validated by manual region-of-interest tracing of the lateral ventricles. Parallel behavioral testing determined the existence of schizophrenia-related sensorimotor gating abnormalities.Results
PolyI:C-induced immune activation, in early but not late gestation, caused marked enlargement of lateral ventricles in adulthood, without affecting total white and grey matter volumes. This early exposure disrupted sensorimotor gating, in the form of prepulse inhibition. Identical immune challenge in late gestation resulted in significant expansion of 4th ventricle volume but did not disrupt sensorimotor gating.Conclusions
Our results provide the first experimental evidence that prenatal immune activation is an environmental risk factor for adult ventricular enlargement relevant to schizophrenia. The data indicate immune-associated environmental insults targeting early foetal development may have more extensive neurodevelopmental impact than identical insults in late prenatal life. 相似文献19.
The Prognostic Value of Phosphorylated AKT Expression in Non-Small Cell Lung Cancer: A Meta-Analysis
Objectives
Phosphorylated AKT (p-AKT), constitutive activation of AKT, is a potentially interesting prognostic marker and therapeutic target in non-small cell lung cancer (NSCLC). However, the available results of p-AKT expression in NSCLC are heterogeneous. Therefore, a meta-analysis of published researches investigating the prognostic relevance of p-AKT expression in patients with NSCLC was performed.Materials and Methods
A literature search via PubMed, EMBASE and CNKI (China National Knowledge Infrastructure) databases was conducted. Data from eligible studies were extracted and included into meta-analysis using a random effects model.Results
A total of 1049 patients from nine studies were included in the meta-analysis. Nine studies investigated the relationship between p-AKT expression and overall survival using univariate analysis, and five of these undertook multivariate analysis. The pooled hazard ratio (HR) for overall survival was 1.49 (95% confidence interval (CI): 1.01-2.20) by univariate analysis and 1.02 (95% CI: 0.54-1.95) by multivariate analysis.Conclusion
Our study shows that positive expression of p-AKT is associated with poor prognosis in patients with NSCLC. However, adequately designed prospective studies need to perform. 相似文献20.
Michael Haimerl Niklas Verloh Florian Zeman Claudia Fellner René Müller-Wille Andreas G. Schreyer Christian Stroszczynski Philipp Wiggermann 《PloS one》2013,8(12)