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

The glutamate/N-methyl-D-aspartate receptor antagonist phencyclidine (PCP) has been shown to induce both positive and negative symptoms of schizophrenia, as well as cognitive deficits, thus providing a relatively valid model of psychosis. Isolation rearing from weaning in the rat has been proposed as a non-pharmacological model of psychosis. The aim of the present study was to explore the validity of a combination of these techniques to model cognitive dysfunction associated with schizophrenia. The present study evaluates the effects of the novel antipsychotic ziprasidone and the typical antipsychotic haloperidol in their ability to reverse the cognitive deficit induced by PCP in isolation reared rats and social controls. Rats housed in social isolation (n = 25) or in groups of five (n = 25) from weaning were food deprived and trained to respond for food in an operant reversal learning paradigm. PCP at 1.0 and 1.5 mg/kg (intraperitoneally, i.p.) significantly and selectively impaired reversal task performance in both groups of rats. This impairment was not significantly improved following the coadministration of haloperidol (0.05 mg/kg, i.p.). Higher haloperidol doses (0.1 and 0.25 mg/kg, i.p.) were found to impair task performance, with the social animals being more sensitive than isolation-reared animals. In contrast, ziprasidone (2.5 mg/kg, i.p.) reversed the impairment caused by PCP. This was significant in social animals, while in isolates there was a non-significant enhancement in performance of the reversal task with ziprasidone compared to PCP alone. Thus, PCP produced a selective reversal learning deficit in rats, which was ameliorated following treatment with ziprasidone but not haloperidol. Rearing conditions did not influence performance of the test or the deficit produced by PCP.
 ...
PMID:The atypical antipsychotic ziprasidone, but not haloperidol, improves phencyclidine-induced cognitive deficits in a reversal learning task in the rat. 1268 Jul 40

Perseveration and switching in positive and negative schizophrenic patients are usually seen as manifestations of attention disorders. They may be closely related to each other, but have not been investigated in an integrated fashion. Such integrated investigation could contribute to the neurophysiological understanding of the relationship between the regional and the pharmacological deficit in schizophrenia. This study has developed a new tool-the Combined Attention Test (CAT)-for the simultaneous measuring of perseveration and switching. Forty-one unmedicated schizophrenic patients were tested. Using the Positive and Negative Sorting Scale (PANSS), subjects were classified into the two experimental groups: positive and negative schizophrenics. The control group consisted of 24 healthy subjects. Schizophrenic patients with positive symptoms tended to switch more than schizophrenic patients with negative symptoms and normal subjects; schizophrenic patients with negative symptoms tended to perseverate more than schizophrenic patients with positive symptoms and normal subjects. Over-switching is discussed as a specific symptom related to positive schizophrenia.
 ...
PMID:Perseveration and over-switching in schizophrenia. 1272 83

This retrospective, cross-sectional study evaluated whether age-related differences in patterns of cognitive deficit exist among four cognitively based schizophrenia subgroups. These subgroups had previously been identified through cluster analyses of a battery of abstraction and problem-solving tests in large samples. Evaluation of estimated premorbid intellectual ability and postmorbid cognitive functioning stratified by decade from the twenties through the fifties revealed different patterns across the schizophrenia subgroups and a clinical comparison sample. A near normal cognitive subgroup demonstrated relatively high premorbid intellectual ability and a pattern of age differences similar to the comparison sample, with the exception of deficits on the Wisconsin Card Sorting Test that were detectable in the twenties and remained stable thereafter. In contrast, a subgroup characterized by severe, pervasive cognitive deficit demonstrated low premorbid intellectual ability and extremely low test scores across the four decades studied. The remaining clusters were characterized by moderate cognitive impairment and showed age differences suggestive of a decline in cognitive function around the time of illness onset that remained stable. Results provide further support for the validity of these subgroups and encourage continued efforts to identify cognitively based candidate schizophrenia subtypes.
 ...
PMID:A retrospective study of premorbid ability and aging differences in cognitive clusters of schizophrenia. 1283 15

The role of genetic factors in liability to schizophrenia is well established. It is supposed that different susceptibility genes produce distinct neurobiological and behavioural phenotypes that may each increase the risk for developing schizophrenia. The aim of the study was to search for genetically and pathophysiologically independent domains of mild cognitive disturbances that might be the components of liability to schizophrenia. One hundred and twenty-seven adult relatives of schizophrenic and schizoaffective patients were tested with a battery of cognitive tasks. Results were subjected to a principal component analysis, and factors obtained were further investigated with behavioural genetic methods in 56 families of schizophrenics. Resting EEGs were recorded from a subsample of 66 relatives. Correlations of the cognitive factors with absolute power values of seven frequency bands at 16 derivations were assessed using regression analysis. The study revealed four components of cognitive deficits in relatives of schizophrenics in domains of verbal short-term memory, thinking, communication and attention/working memory, all with substantive heritability except the last. The four components had a partial overlapping, but still distinct patterns of resting EEG correlates. The findings are in line with the assumption that cognitive deficit in high-risk individuals may be decomposed to relatively independent dimensions, each with its specific genetic and pathophysiological background.
 ...
PMID:Cognitive peculiarities in relatives of schizophrenic and schizoaffective patients: heritability and resting EEG-correlates. 1450 39

Cognitive deficits are a key feature of schizophrenia. N-Methyl-D-aspartate (NMDA) receptor antagonists and amphetamine are known to induce psychotic behaviors and cognitive deficits in animals and humans, often affecting visuo-spatial abilities. Phencyclidine (PCP), MK-801 and amphetamine (AMPH) have been used in pharmacological animal models of schizophrenia, but none of these models has focused so far on spatial learning after repeated administration of the drugs. The objective of this study was to test whether repeated administration of PCP, AMPH or MK-801 influenced the performance of mice in a non-associative spatial learning test. CD-1 male mice were given i.p. daily injections of either saline, PCP (5.0, 10.0 mg/kg), AMPH (2.5, 5 mg/kg) or MK-801 (0.3, 0.6 mg/kg), for 5 days. On day 6 all mice were tested in an open field containing five different objects. After three sessions of habituation, each animal's reactivity to object displacement and object substitution was assessed. No significant differences among treatment groups were observed in object exploration or locomotion during the habituation phase. Five days of repeated PCP, AMPH or MK-801 administration selectively and differentially impaired the ability of mice to discriminate a spatial change, while leaving intact the ability to react to a non-spatial change. These data suggest that neurobiological adaptations to drug regimens known to induce psychotic behaviors and alterations in locomotor activity or stereotypies can also alter spatial learning, as assessed in this test, thus indicating that these regimens could also mimic some of the cognitive deficits observed in schizophrenia.
 ...
PMID:Repeated administration of phencyclidine, amphetamine and MK-801 selectively impairs spatial learning in mice: a possible model of psychotomimetic drug-induced cognitive deficits. 1455 21

It has recently been suggested that sigma receptors are involved in psychiatric disorders. Sigma 1 receptor antagonists are effective in animal models of positive symptoms, cognitive deficit and disruption of prepulse inhibition in schizophrenia. They also inhibit the development and expression of the conditioned place preference induced by cocaine. On the other hand, sigma 1 receptor agonists reduce the immobility time in the forced swimming and tail suspension tests. Furthermore, sigma 1 receptor agonists attenuate the conditioned fear stress (CFS) response (which is not attenuated by typical anxiolytics or antidepressants) in rodents. The attenuating effects are mediated through sigma 1 receptors, which are closely related to the mesolimbic dopaminergic systems. Sigma 1 receptor agonists also have anti-amnesic effects in various experimental models. Neurosteroids such as dehydroepiandrosterone sulfate and pregnenolone sulfate attenuate the CFS response and have anti-amnesic effects, the effects being mediated via sigma 1 receptors. These findings suggest that sigma receptors are novel potential targets for the treatment of psychiatric disorders such as schizophrenia, drug abuse, depression and dementia.
 ...
PMID:[Effects of sigma receptor ligands on psychiatric disorders]. 1465 24

Cognitive deficits have been associated with poorer function and quality of life (QOL) in schizophrenia, but no similar findings have been confirmed in persons with major depressive episode (MDE). We investigated whether cognitive deficits were associated with detrimental effects on the QOL of persons with primary MDE. Seventy-seven non-demented adults with MDE underwent evaluations of mood, cognition and QOL. Cognition was assessed with the Mini-Mental State Exam, and delayed recall on the Rey Auditory Verbal Learning Task and the Rey Figure. QOL assessments included instrumental activities of daily living (IADL), activities of daily living (ADL), and satisfaction in role functioning and relationships. Univariate correlation and regression models were used to find those mood and cognitive variables most closely related to each QOL dimension. ADL function and satisfaction with role functioning and relationships were most closely related to depression severity and age. IADL functioning, however, was most closely associated with global cognition. This study did not take into account the physical health of the participants, and all the participants were seriously ill with depression. Thus, the results may not apply to persons with less severe MDE. Antidepressant treatments that preserve or enhance global cognition in addition to relieving core depressive symptoms may lead to the best functional outcomes.
 ...
PMID:Cognitive deficits are associated with functional impairment in severely depressed patients. 1465 52

It has been suggested that perinatal treatment with the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist phencyclidine (PCP) induces transient neurodegeneration in the limbic and cortical structures of rats. Since dysfunction of these structures is associated with cognitive deficits in patients with schizophrenia, we studied the effects of subchronic treatment with PCP in perinatal rats with respect to spatial reference, reversal, and spatial working memories using the Morris water maze task in adulthood. In addition, we investigated the effect of D-serine, which has clinical relevance for the treatment of cognitive deficits in patients with schizophrenia. Our goal was to develop a neurodevelopmental model with predictive validity for the cognitive dysfunction described in patients with schizophrenia. Male and female Sprague-Dawley rats were treated with either saline or PCP (8.7 mg/kg s.c.) on days 7, 9, and 11, postnatal, and the long-term behavioral effects were investigated in adulthood. Male PCP-treated rats were slightly impaired during the spatial reference memory task, but strongly impaired during the reversal and spatial working memory tasks. Female rats were not significantly affected by this treatment. This cognitive deficit was reversed by chronic treatment with D-serine. We suggest that this model mimics some of the cognitive deficits of patients with schizophrenia and might be appropriate for the screening of putative antipsychotic agents for the treatment of these cognitive deficits.
 ...
PMID:Spatial memory deficits induced by perinatal treatment of rats with PCP and reversal effect of D-serine. 1497 Aug 28

In order to clarify the feature of attention disorders in schizophrenia, two tasks (X and AX) of the Continuous Performance Test (CPT) were given to 36 schizophrenic patients and 25 healthy controls. The schizophrenic patients performed considerably less well than normal controls. Performances were expressed in indices such as omission and commission errors, reaction time and discriminability. Among errors, omission in both the X and AX tasks was found to be an index that varied in reaction time, indicating difficulty in sustaining attention. Omission was found to act as a state-dependent index of schizophrenia in relation to inattentiveness in clinical settings and emotional disturbance in interpersonal situations. Commission, in contrast, differed between the two tasks, acting as an index of disinhibition of reaction in the X task, and of disturbance of the capacity and allocation of attention in the AX task. Commission was also thought to be an index related to thought disorder during episodes of acute schizophrenia, that is, it reflects an essential pathology in schizophrenia.
 ...
PMID:Attention disorders in schizophrenia. 1514 89

Cognitive deficits and neurological soft signs (NSS) have frequently been reported in schizophrenic patients and they both appear related to prominent negative symptoms. The aim of the present study was to examine the relationship between deficit of executive functioning, assessed by the Wisconsin Card Sorting Test (WCST), NSS and psychopathological dimensions of schizophrenia in order to address the issue of whether a typology of schizophrenic patients may be identifiable by clinical, neurological and neuropsychological features. A sample of 26 male schizophrenic patients was divided, on the basis of the performance on the WCST, into two subgroups ('good performers' and 'poor performers') that were compared for the prevalence and severity of NSS, assessed by the Neurological Evaluation Scale (NES), and for the psychopathological features, assessed using the Positive and Negative Syndrome Scale (PANSS). To test for between-group differences, ANOVA was conducted. The 'poor performers' group showed greater severity of NSS: significant differences emerged for the NES total score and for the 'sequencing of complex motor acts' score. However, no significant differences between the groups emerged for any PANSS score. These findings seem to indicate that a common neurobiological abnormality could underlie cognitive deficits, especially concerning executive functioning, and subtle neurological abnormalities often present in schizophrenia, but they appear to deny that such dysfunctional correlates of schizophrenia are related to a prominent negative symptomatology.
 ...
PMID:Deficit of executive functions in schizophrenia: relationship to neurological soft signs and psychopathology. 1515 43


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>