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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Analysis of single-trial event-related potentials can potentially yield important information about the underlying brain dynamics. We were specifically interested in latency and amplitude variability of the P3 component in patients with schizophrenia. For this purpose we developed a method for analyzing single-trial ERPs based on a wavelet smoothing algorithm, which is presented in detail. This method was applied to data from schizophrenic patients and healthy controls in an auditory Go/Nogo task. We found a significant increase of latency variability in the schizophrenic group at electrode Fz (frontal midline) and increased amplitude variability at electrode Pz (parietal midline). These results support the concept of increased cortical noise in patients with schizophrenia.
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PMID:Increased event-related potential latency and amplitude variability in schizophrenia detected through wavelet-based single trial analysis. 1790 Jul 25

The majority of psychopathology is rooted early in life and first emerges during childhood and adolescence. However, little is known about how risk genes affect brain function to increase biological vulnerability to psychopathology in childhood, because most imaging genetic studies published so far have been conducted on adult participants. We examined the impact of neuregulin1 (NRG1), a probable susceptibility gene for schizophrenia and bipolar disorder, on brain function in a sample of 102 ten- to twelve-year-old children. Each participant performed a Go/Nogo task, whereas brain responses were measured using functional magnetic resonance imaging. Statistical parametric mapping was used to estimate the impact of genetic variation in NRG1 on brain activation. Response accuracy and reaction times did not differ as a function of NRG1 genotype. However, individuals with the high-risk variant expressed greater brain activation for both Go and Nogo stimuli in the right posterior orbital gyrus, where NRG1 genotype accounted for 11% of interindividual variance. There were no regions showing a significant interaction between NRG1 genotype and stimulus type even at trend level, suggesting that the impact of NRG1 on brain activation was not specific to either response inhibition or motor execution. These results suggest that that genetic variation in NRG1 is associated with different levels of prefrontal engagement in children as young as 10-12 years of age. Our investigation provides support to the idea that genetic factors may affect brain function to moderate vulnerability to psychopathology from childhood.
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PMID:Genetic variation in neuregulin1 is associated with differences in prefrontal engagement in children. 1944 32

The membrane protein Nogo-A, which is predominantly expressed by oligodendrocytes in the adult CNS and by neurons mainly during development, is well known for limiting neurite outgrowth and regeneration in the injured mammalian CNS. In addition, it has recently been proposed that abnormal Nogo-A expression or Nogo receptor (NgR) mutations may confer genetic risks for neuropsychiatric disorders of presumed neurodevelopmental origin, such as schizophrenia. We therefore evaluated whether Nogo-A deletion may lead to schizophrenia-like abnormalities in a mouse model of genetic Nogo-A deficiency. Here, we show that systemic, lifelong knock-out of the Nogo-A gene can lead to specific behavioral abnormalities resembling schizophrenia-related endophenotypes: deficient sensorimotor gating, disrupted latent inhibition, perseverative behavior, and increased sensitivity to the locomotor stimulating effects of amphetamine. These behavioral phenotypes were accompanied by altered monoaminergic transmitter levels in specific striatal and limbic structures, as well as changes in dopamine D2 receptor expression in the same brain regions. Nogo-A deletion was further associated with elevated expression of growth-related markers. In contrast, acute antibody-mediated Nogo-A neutralization in adult wild-type mice failed to produce such phenotypes, suggesting that the phenotypes observed in the knock-out mice might be of developmental origin, and that Nogo-A normally subserves critical functions in neurodevelopment. This study provides the first experimental demonstration that Nogo-A bears neuropsychiatric relevance, and alterations in its expression may be one etiological factor in schizophrenia and related disorders.
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PMID:Constitutive genetic deletion of the growth regulator Nogo-A induces schizophrenia-related endophenotypes. 2007 18

Intra-individual variability of reaction times (IIV) can be employed as a measure of the stability of information processing, which has been proposed to be fundamentally disturbed in schizophrenia. However, the theoretical and clinical significance of IIV is not clear, in part because it has previously been investigated in subject groups with generalized cognitive impairment. Therefore, the purpose of the study was to assess IIV in high-functioning patients with schizophrenia and relatively preserved cognitive performance. 28 high-functioning patients with schizophrenia and 28 controls performed a Go/Nogo task and a Continuous Performance Test. In contrast to average measures of task performance, IIV differentiated consistently and with large effect size between groups. Modelling with an Ex-Gaussian distribution revealed that patients have a higher proportion of slow responses reflected by an increased tau parameter. The tau parameter was correlated with work capability in the sample with schizophrenia. In conclusion, IIV is an easily obtained measure, which is highly sensitive to fundamental cognitive deficits not directly visible in a high-functioning patient group. The response pattern with more exceedingly slow reactions could reflect a core deficit in the stability of information processing. The relationship with work capability suggests investigation of IIV as a clinical measure.
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PMID:Intra-individual variability in high-functioning patients with schizophrenia. 2044 95

Many studies have suggested that myelin dysfunction may be causally involved in the pathogenesis of schizophrenia. Nogo (RTN4), myelin-associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein (OMG) all bind to the common receptor, Nogo-66 receptor 1 (RTN4R). We examined 68 single nucleotide polymorphisms (SNPs) (51 with genotyping and 17 with imputation analysis) from these four genes for genetic association with schizophrenia, using a 2,120 case-control sample from the Japanese population. Allelic tests showed nominally significant association of two RTN4 SNPs (P = 0.047 and 0.037 for rs11894868 and rs2968804, respectively) and two MAG SNPs (P = 0.034 and 0.029 for rs7249617 and rs16970218, respectively) with schizophrenia. The MAG SNP rs7249617 also showed nominal significance in a genotypic test (P = 0.017). In haplotype analysis, the MAG haplotype block including rs7249617 and rs16970218 showed nominal significance (P = 0.008). These associations did not remain significant after correction for multiple testing, possibly due to their small genetic effect. In the imputation analysis of RTN4, the untyped SNP rs2972090 showed nominally significant association (P = 0.032) and several imputed SNPs showed marginal associations. Moreover, in silico analysis (PolyPhen) of a missense variant (rs11677099: Asp357Val), which is in strong linkage disequilibrium with rs11894868, predicted a deleterious effect on Nogo protein function. Despite a failure to detect robust associations in this Japanese cohort, our nominally positive signals, taken together with previously reported biological and genetic findings, add further support to the "disturbed myelin system theory of schizophrenia" across different populations.
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PMID:Association study of Nogo-related genes with schizophrenia in a Japanese case-control sample. 2156 1

The reticulon-4 receptor, encoded by RTN4R, limits axonal sprouting and neural plasticity by inhibiting the outgrowth of neurites. Human association studies have implicated mutations in RTN4R in the development of schizophrenia, including the identification of several rare nonconservative missense mutations of RTN4R in schizophrenia patients. To investigate the effects of missense mutation of the reticulon-4 receptor on phenotypes relevant to schizophrenia, we behaviourally characterized a novel Rtn4r mutant mouse line with an amino acid substitution (R189H) in the Nogo-66 binding site. Behavioural assays included prepulse inhibition of acoustic startle, locomotor activity, social interaction and spatial cognition. When compared with wildtype littermates, Rtn4r mutant mice exhibited greater social preference, which may reflect a social-anxyolitic effect, and a mild impairment in spatial cognition. Given the mild effect of the R189H mutation of Rtn4r on behavioural phenotypes relevant to schizophrenia, our results do not support missense mutation of RTN4R as a strong risk factor in the pathogenesis of schizophrenia.
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PMID:Missense mutation of the reticulon-4 receptor alters spatial memory and social interaction in mice. 2164 50

Recent theories of schizophrenia have proposed a fundamental instability of information processing on a neurophysiological level, which can be measured as an increase in latency variability of event-related potentials (ERPs). If this reflects a fundamental deficit of the schizophrenic illness, it should also occur in high-functioning patients. These patients have also been observed to show a more diffuse activation pattern in neuroimaging studies, which is thought to reflect compensatory processes to maintain task performance. In the present study we investigated temporal variability and spatial diffusion of the visual N2 component in a group of high-functioning patients with preserved cognitive performance. 28 patients with schizophrenia and 28 control participants matched for gender, age and education participated in the study. Subjects performed a visual Go/Nogo task, while event-related potentials were obtained. Trial-to-trial latency variability was calculated with a Wavelet-based method. Patients with schizophrenia showed a robust increase in N2 latency variability at electrodes Fz and Cz in all task conditions. Regarding spatial distribution healthy participants showed a focused fronto-central N2 peak. In contrast, patients with schizophrenia showed a more diffuse pattern and additional negative peaks over lateral electrodes in the Nogo condition. These results clearly show that even in high-functioning patients with schizophrenia a higher temporal variability of ERPs can be observed. This provides support for temporal instability of information processing as a fundamental deficit associated with schizophrenia. The more diffuse scalp distribution might reflect processes that compensate for this instability when cognitive control is required.
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PMID:Temporal variability and spatial diffusion of the N2 event-related potential in high-functioning patients with schizophrenia. 2174 25

The membrane protein Nogo-A and its receptor NgR have been extensively characterized for their role in restricting axonal growth, regeneration, and plasticity in the central nervous system. Recent evidence suggests that Nogo and NgR might constitute candidate genes for schizophrenia susceptibility. In this article, we critically review the possibility that dysfunctions related to Nogo-A and NgR might contribute to increased risk for schizophrenia. To this end, we consider the most important insights that have emerged from human genetic and pathological studies and from experimental animal work. Furthermore, we discuss potential mechanisms of Nogo/NgR involvement in neural circuit development and stability, and how mutations or changes in expression levels of these proteins could be developmental risk factors contributing to schizophrenia.
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PMID:Nogo and Nogo receptor: relevance to schizophrenia? 2336 71

We have generated a transgenic rat model using RNAi and used it to study the role of the membrane protein Nogo-A in synaptic plasticity and cognition. The membrane protein Nogo-A is expressed in CNS oligodendrocytes and subpopulations of neurons, and it is known to suppress neurite growth and regeneration. The constitutively expressed polymerase II-driven transgene was composed of a microRNA-targeting Nogo-A placed into an intron preceding the coding sequence for EGFP, thus quantitatively labeling cells according to intracellular microRNA expression. The transgenic microRNA in vivo efficiently reduced the concentration of Nogo-A mRNA and protein preferentially in neurons. The resulting significant increase in long-term potentiation in both hippocampus and motor cortex indicates a repressor function of Nogo-A in synaptic plasticity. The transgenic rats exhibited prominent schizophrenia-like behavioral phenotypes, such as perseveration, disrupted prepulse inhibition, and strong withdrawal from social interactions. This fast and efficient microRNA-mediated knockdown provides a way to silence gene expression in vivo in transgenic rats and shows a role of Nogo-A in regulating higher cognitive brain functions.
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PMID:Synthetic microRNA-mediated downregulation of Nogo-A in transgenic rats reveals its role as regulator of synaptic plasticity and cognitive function. 2357 23

It has been suggested that Nogo-A, a myelin-associated protein, could play a role in the pathogenesis of schizophrenia and that Nogo-A-deficient rodents could serve as an animal model for schizophrenic symptoms. Since changes in brain laterality are typical of schizophrenia, we investigated whether Nogo-A-deficient rats showed any signs of disturbed asymmetry in cortical N-methyl-d-aspartate (NMDA) receptor-nitric oxide synthase (NOS) pathway, which is reported as dysfunctional in schizophrenia. In particular, we measured separately in the right and left hemisphere of young and old Nogo-A-deficient male rats the expression of NMDA receptor subunits (NR1, NR2A, and NR2B in the frontal cortex) and activities of NOS isoforms [neuronal (nNOS), endothelial (eNOS), and inducible (iNOS) in the parietal cortex]. In young controls, we observed right/left asymmetry of iNOS activity and three positive correlations (between NR1 in the left and NR2B laterality, between NR2B in the right and left sides, and between NR1 in the right side and nNOS laterality). In old controls, we found bilateral decreases in NR1, an increase in NR2B in the right side, and two changes in correlations in the NR1-nNOS pathway. In young Nogo-A-deficient rats, we observed an increase in iNOS activity in the left hemisphere and two changes in correlations in NR1-nNOS and NR2A-eNOS, compared to young controls. Finally, we revealed in old Nogo-A-deficient animals, bilateral decreases in NR1 and one change in correlation between eNOS-iNOS, compared to old controls. Although some findings from schizophrenic brains did not manifest in Nogo-A-deficient rats (e.g., no alterations in NR2B), others did (e.g., alterations demonstrating accelerated aging in young but not old animals, those occurring exclusively in the right hemisphere in young and old animals and those suggesting abnormal frontoparietal cortical interactions in young animals).
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PMID:N-Methyl-d-Aspartate Receptor - Nitric Oxide Synthase Pathway in the Cortex of Nogo-A-Deficient Rats in Relation to Brain Laterality and Schizophrenia. 2396 13


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