Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Findings of white matter pathology as indicated by diffusion tensor anisotropy values in schizophrenia are well established, but the differences in this measure between the onset of the disease and the chronic state are not well known. To investigate the differences between these states in the progression of the disease of schizophrenia we acquired 1.5 T diffusion tensor anisotropy images on 35 adult patients with schizophrenia and schizoaffective disorder, 23 adolescents having their first psychotic episode, and age and sex matched controls (33 adults and 15 adolescents). Regions of interest in major cortical white matter tracts chosen as salient to the prefrontal executive deficit in schizophrenia were assessed using stereotaxic coordinates from the Talairach and Tournoux atlas. Regions of each tract along anterior-posterior and/or inferior-superior directions in both hemispheres were evaluated in multiway ANOVA. Tracts between the frontal lobe and other brain regions, but not temporal, occipital and interhemispheric tracts, showed a differential aging pattern in normals and patients indicating that the white matter pathology in these regions is not stable between the onset and the chronic state in schizophrenia. This suggests that tracts involved in the connectivity of the temporal lobe white matter deficits were already well in place in adolescent patients, while frontal lobe pathology continues to develop from adolescence to adulthood.
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PMID:Age and diffusion tensor anisotropy in adolescent and adult patients with schizophrenia. 1916 39

D-Serine, an endogenous amino acid, is involved in many physiological processes through its interaction with the glycine binding site of the N-methyl-D-aspartate (NMDA) receptor. It has important roles in development, learning, and cell death signaling. Recent evidence suggests that decreased function of the NMDA receptor is related to the etiology of schizophrenia, and the use of D-serine as add-on therapy is beneficial in alleviating the symptoms of treatment-refractory schizophrenia. The NMDA receptor also plays a major role in neuronal cell death and neurodegeneration mediated by excitatory amino acid toxicity in ischemia, epilepsy, and trauma. Due to its co-activator function, D-serine can markedly potentiate NMDA-mediated excitotoxicity. To investigate potential adverse effects of D-serine treatment, we investigated gene expression changes in the forebrain of male F-344 rats treated with a single intraperitoneal injection of D-serine (5, 20, 50, 200, or 500 mg/kg) at 96 h post-treatment. Gene expression profiling using Affymetrix Rat Genome 230 2.0 arrays revealed that D-serine treatment resulted in up- and down-regulation of 134 and 52 genes, respectively, based on the common genes identified using three statistical methods, i.e. t test (p < 0.01 over two consecutive doses), ANOVA (with adjusted Bonferonni correction for multiple testing) and significance analysis of microarray (SAM). Self organized map (SOM) clustering analysis of the differentially expressed genes showed two clusters, one with all 134 up-regulated probe sets and the other with all 52 down-regulated probe sets. The dose-response pattern of the down-regulated cluster showed nearly a perfect mirror image of that of the up-regulated one. Gene ontology analysis revealed that pathways implicated in neuronal functions and/or neurodegenerative disorders are over-represented among the differentially expressed genes. Specifically, genes involved in vesicle-mediated transport, endocytosis, ubiquitin conjugation pathway, regulation of actin filament polymerization/depolymerization, focal adhesion, Wnt signaling, and insulin signaling were up-regulated, while genes involved in RNA metabolism/splicing/processing and Notch signaling were down-regulated. Consistent with this finding, pathway analysis using GenMAPP showed a significant number of differentially expressed genes in these pathways. In addition, the GenMAPP result also showed activation of the signaling pathways of several proinflammatory cytokines (including IL-2, IL-3, IL-5, IL-6 and TNF-alpha), which might suggest the onset of neuroinflammation. Biological association network analysis showed that several nuclear factors implicated in transcription regulation (including Taf1, Max, Myc, and Hnf4a) are highly connected to a large number of up-regulated genes. While the transcript levels of these transcription factors were not changed, their connections to Ddx3x, a gene involved in mRNA processing and translation initiation, raise the possibility that they may be up-regulated at the post-transcriptional level. The observation that Ubqln1 and Ube2d, two differentially expressed genes involved in ubiquitin-mediated proteolysis and implicated in neurodegenerative disorders, are highly connected in this network suggests a role of ubiquitination proteasome pathway in response to D-serine exposure. This finding is consistent with the result of gene ontology analysis and suggests that D-serine treatment might result in damage to cellular proteins and subsequent up-regulation of ubiquitination proteasome pathway to clear these damaged proteins. In summary, D-serine exposure resulted in perturbation of a number of pathways implicated in neuronal functions and neurodegenerative disorders. However, activation of cellular response to counter the toxic effects of D-serine might be hindered due to the down-regulation of such important cellular machinery like RNA metabolism, splicing and processing. Consequently, cell damage might be further exacerbated. Taken together, these findings highlight the potential impacts of D-serine exposure on neuronal functions.
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PMID:D-Serine exposure resulted in gene expression changes implicated in neurodegenerative disorders and neuronal dysfunction in male Fischer 344 rats. 1921 59

Recent neuroimaging studies have reported deficits in functional integration between prefrontal cortex and the hippocampal formation in schizophrenia. It is unclear whether these alterations are a consequence of chronic illness or its treatment, and whether they are also evident in non-psychotic subjects at increased risk of the disorder. We addressed these issues by investigating prefrontal-hippocampal interactions in patients with first episode schizophrenia and subjects with an At Risk Mental State (ARMS). Using functional Magnetic Resonance Imaging, we measured brain responses from 16 individuals with an ARMS, 10 patients with first episode schizophrenia and 14 healthy controls during a delayed matching to sample task. Dynamic causal modelling was used to estimate the effective connectivity between prefrontal cortex and anterior and posterior hippocampal regions. The normal pattern of effective connectivity from the right posterior hippocampus to the right inferior frontal gyrus was significantly decreased in both first episode patients and subjects with an ARMS (ANOVA; F = 8.16, P = 0.01). Interactions between the inferior frontal gyrus and the anterior part of the hippocampus did not differ across the three groups. Perturbed hippocampal-prefrontal interactions are evident in individuals at high risk of developing psychosis and in patients who have just developed schizophrenia. This suggests that it may be a correlate of increased vulnerability to psychosis and that it is not attributable to an effect of chronic illness or its treatment.
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PMID:Functional integration between the posterior hippocampus and prefrontal cortex is impaired in both first episode schizophrenia and the at risk mental state. 1942 91

Research has indicated that many with schizophrenia experience deficits in metacognitive capacity, defined as impairments in the ability to think about thinking. These difficulties are related to, but not reducible to symptoms and have been hypothesized to function as an independent impediment to psychosocial function. To explore the possibility that deficits in one domain of metacognition, self-reflectivity, are a barrier to effective work function, 56 participants with schizophrenia were categorized into three groups according to their capacity for self reflection based on an interview conducted prior to accepting a job placement. Blind ratings of work performance of these three groups over the next six months were then compared. Results of repeated measures ANOVA revealed that the group rated as having the highest level of metacognition, that is, able to see that their conclusions are subjective and fallible, had higher ratings of work performance over time than groups with medium and low levels of self reflectivity. These findings were found to persist even when impairment on a test of executive function was controlled for statistically. Results are interpreted as consistent with emerging models that deficits in metacognition may be key features of severe mental illness which affect function. Clinical and theoretic implications are discussed.
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PMID:Metacognition and schizophrenia: the capacity for self-reflectivity as a predictor for prospective assessments of work performance over six months. 1945 45

Dopamine has a crucial role in the modulation of neurocognitive function, and synaptic dopamine activity is normally regulated by the dopamine transporter (DAT) and catechol-O-methyltransferase (COMT). Perturbed dopamine function is a key pathophysiological feature of schizophrenia. Our objectives were (i) to examine epistasis between the DAT 3' UTR variable number of tandem repeats (VNTR) and COMT Val158Met polymorphisms on brain activation during executive function, and (ii) to then determine the extent to which such interaction is altered in schizophrenia. Regional brain response was measured by using blood-oxygen-level-dependent fMRI during an overt verbal fluency task in 85 subjects (44 healthy volunteers and 41 patients with DSM-IV schizophrenia), and inferences were estimated by using an ANOVA in SPM5. There was a significant COMT x DAT nonadditive interaction effect on activation in the left supramarginal gyrus, irrespective of diagnostic group (Z-score = 4.3; family-wise error (FWE) p = 0.03), and in healthy volunteers alone (Z-score = 4.7; FWEp = 0.006). In this region, relatively increased activation was detected only when COMT Met-158/Met-158 subjects also carried the 9-repeat DAT allele, or when, reversely, Val-158/Val-158 subjects carried the 10/10-repeat genotype. Also, there was a significant diagnosis x COMT x DAT nonadditive interaction in the right orbital gyrus (Z-score = 4.3; FWEp = 0.04), where, only within patients, greater activation was only associated with a 9-repeat allele and Val-158 conjunction, and with a 10-repeat and Met-158 conjunction (Z-score = 4.3; FWE p = 0.04). These data demonstrate that COMT and DAT genes interact nonadditively to modulate cortical function during executive processing, and also, that this effect is significantly altered in schizophrenia, which may reflect abnormal dopamine function in the disorder.
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PMID:Epistasis between the DAT 3' UTR VNTR and the COMT Val158Met SNP on cortical function in healthy subjects and patients with schizophrenia. 1966 77

Cognitive dysfunction is a chronically disabling feature of schizophrenia, associated with limits in obtaining rehabilitation improvements. The purpose of this study is to assess the effectiveness of intensive computer-aided cognitive remediation treatment (CRT) added to a standard rehabilitation treatment (SRT), in enhancing neuropsychological performances and daily functioning in patients with schizophrenia. A 12-week, randomized, controlled, single-blind trial of neurocognitive remediation was carried out on 86 patients with clinically stabilized DSM-IV schizophrenia. Patients were assessed on cognitive and daily functioning before and after either CRT or placebo training that had been added to their SRT. After 3 months the repeated measure ANOVA showed a significant time x treatment interaction for executive function and attention performances and in daily functioning assessment in favour of patients in the SRT+CRT treatment. Results confirmed that cognitive remediation added to the SRT of schizophrenia enhanced its neuropsychological effects and increased the effects of a long-term rehabilitation programme in terms of functional outcomes.
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PMID:Computer-aided neurocognitive remediation as an enhancing strategy for schizophrenia rehabilitation. 1974 May 50

Advanced parental age has been shown to increase offspring risk for a number of neuropsychiatric disorders including schizophrenia and Down's syndrome. Other psychiatric disorders have been less studied with respect to the effect of parental age on offspring risk. In this study we examine if advanced parental age increased risk for ICD-10 diagnoses. We hypothesized that advanced parental age would increase risk for offspring psychotic disorders and mental retardation but not other ICD-10 diagnoses. We examined follow-up data for 30,965 subjects treated in outpatient psychiatric facilities between 1980 and 2007. Subjects were younger than 18 years of age at their first outpatient visit. A comparison group was obtained from data on registered births in Spain from 1975. We compared parental age (maternal, paternal, combined) across diagnostic categories using ANOVA and logistic regression was used to estimate the risk of psychopathology in the offspring with advanced parental age (maternal, paternal, combined). Maternal and paternal ages were higher for subjects diagnosed with mental retardation. Risk for psychotic disorders showed a significant linear increase only with advancing maternal age, and not paternal age as is more often reported.
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PMID:Differences in maternal and paternal age between schizophrenia and other psychiatric disorders. 1994 57

This study investigated gamma-band activity (GBA) and its phase synchrony in schizophrenia patients viewing human faces. Twenty-five schizophrenia patients were compared with 25 normal controls. Event-related potentials were recorded from all participants while they were viewing emotionally neutral faces. The spectral power and phase synchrony in the frequency band from 30 to 55 Hz were analyzed in midline electrodes (FCz, Cz, CPz, Pz, and POz). Three windows of interest, which showed discernable GBA differences between schizophrenia patients and normal controls, were selected by visual inspection: 0-100 ms (30-33 Hz), 250-300 ms (34-38 Hz), and 700-800 ms (40-45 Hz). And the phase synchrony of gamma band was analyzed. Repeated-measures ANOVA revealed that the GBA was lower in schizophrenia patients than in normal controls. Also there were significant location and time differences in GBA. GBA was significantly lower in the schizophrenia patients than in the normal controls at around 700-800 ms at the FCz electrode. The frontal (FCz) and central (Cz) GBA were significantly correlated with the number of hospitalization, and the negative symptoms of schizophrenia, respectively. The phase synchronization was significantly lower at 200-300 ms in the schizophrenia patients than in the normal controls. These findings suggest that the schizophrenia patients have impaired GBA and gamma-band synchronization during face perception. Furthermore, our results also suggest that the decreased GBA observed at the midline cortex of schizophrenia patients is closely related to their negative symptoms and disease progress.
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PMID:Dysfunctional gamma-band activity during face structural processing in schizophrenia patients. 2030 13

Patients with schizophrenia exhibit decreased neuregulin 1 (NRG1)-stimulated AKT phosphorylation in peripheral lymphoblasts. Here, we examined this peripheral marker in monozygotic twins discordant for schizophrenia and in healthy monozygotic twins without psychiatric disorders. B lymphoblasts were stimulated with NRG1a (65 amino-acid residue recombinant protein from the epidermal growth factor [EGF] domain) for 30min. The protein isolated from the cells was analysed by Western blotting. The dependent measure was the ratio of phosphorylated AKT (pAKT) and total AKT at baseline (without NRG1 stimulation) and after NRG1 stimulation (pAKT/AKT). The results revealed that in the case of the unaffected co-twins of patients with schizophrenia, NRG1-stimulated pAKT/AKT ratio was in between the values of their co-twins with schizophrenia and that of the healthy control twin pairs. When the affected twins with schizophrenia were compared with their unaffected co-twins using a Mann-Whitney U-test, we found significantly lower NRG1-induced pAKT/AKT ratios in the patients relative to their unaffected co-twins (p=0.004). However, using a more conservative analysis (Kruskal-Wallis ANOVA followed tests for multiple comparisons), this difference was not significant. The unaffected co-twins of patients with schizophrenia did not differ significantly from the healthy control twins. In the baseline condition, the pAKT/AKT ratios were similar in all groups. These results indicate that impaired AKT-related intracellular signaling is partly related to the developed illness and cannot fully be explained by the genetic background of schizophrenia.
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PMID:Neuregulin 1-induced AKT phosphorylation in monozygotic twins discordant for schizophrenia. 2037 Dec 57

The study aimed to evaluate the efficacy of long-acting injectable risperidone (LAR) in Asian patients with schizophrenia spectrum disorders. Twenty-five patients enrolled in this 6-month open labelled study. They were switched from their current antipsychotic to LAR without a prior oral risperidone run-in phase. Efficacy was assessed by the positive and negative syndrome scale (PANSS) and clinical global impression (CGI) scales. Extra-pyramidal side effects (EPSE) was assessed using the Simpson Angus Scale (SAS), and weight and plasma levels of fasting blood glucose, lipids and prolactin were measured. Baseline and last visits differences were tested by paired t-test and Wilcoxon signed-rank test; ratings measured over time were analysed using repeated measures ANOVA. Participants' mean age was 30.3 (+/-6.6) years. Principal reason for switching to LAR was non-compliance (40.0%). Thirteen (52%) patients completed the trial. Over 6 months, there were significant reductions in total PANSS (p = 0.008) and CGI (p = 0.001) scores. There were significant increases in weight (p < 0.001), levels of plasma cholesterol and fasting glucose. LAR was effective in improving symptom severity within the first month of starting treatment. However, significant increases in weight and plasma levels of fasting glucose and cholesterol raise concern about metabolic side effects.
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PMID:Safety and efficacy of long-acting injectable risperidone in patients with schizophrenia spectrum disorders: a 6-month open-label trial in Asian patients. 2037 74


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