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

BPD is often associated with cognitive deficits that tend to be present regardless of mood state. Greater impairments tend to be seen in BPD patients who are older, have an early onset of the disease, and suffer a more severe course of illness. The literature also suggests that cognitive deficits are present early in patients with BPD and may be cumulative, showing an association with the number of affective (particularly depressed) episodes over time. Cognitive deficits in BPD may share some common characteristics with those seen in patients with schizophrenia, although the latter tend to show much greater and generalized cognitive impairment. For example, unlike patients with schizophrenia, patients with BPD typically do not score lower than normal persons on measures of global intellectual ability. There also is not overwhelming evidence of laterality or localization of cognitive deficits in BPD, although debate in the literature continues. More visuospatial deficits tend to be found in BPD and UPD than in schizophrenia, thereby raising the possibility of greater involvement of right hemisphere systems in mood disorders. In general, despite variability across investigations, deficits in executive functioning, episodic memory,sustained concentration, and, to a lesser extent, visuospatial skills seem to be the most consistent areas of impairment in BPD. Just as neuroimaging anomalies have been well documented in schizophrenia, structural brain abnormalities have been noted in BPD,most commonly involving the basal ganglia or white matter. Specific comparisons of cerebral atrophy and ventricular size between patients with schizophrenia and BPD have not been definitive, making it difficult to draw conclusions about structural brain abnormalities that might be specific to BPD. Nonetheless, there is enough evidence to suggest that white-matter abnormalities are reported with a greater frequency in BPD patients than in patients with UPD or schizophrenia. Functional neuro-imaging studies of mood disorders have indicated that the frontal cortex,basal ganglia, and temporal lobes are involved. The relationships between neuroimaging and neurocognitive abnormalities in BPD are worthy of additional investigation. Clearly, efforts directed toward phenotyping neuropsychiatric disorders using such measures, in addition to other clinical, neuroimaging, neurophysiologic, and genotypic information, may yield important insights into the development, nature, and course of illness. It is hoped that this understanding will lead to better identification of individuals who may be prone to greater cognitive impairment or decline and those who might be more responsive to specific treatments.
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PMID:Cognition in bipolar disorder. 1582 41

The active moiety of clozapine, the prototypical antipsychotic drug, consists of clozapine and its major metabolite, N-desmethylclozapine (NDMC). Previous studies have suggested that NDMC may be more important than the patent compound itself for the improvement in cognition in patients with schizophrenia treated with clozapine. While the pharmacology of clozapine and NDMC are similar in most respects, NDMC has been shown to be an M1 muscarinic receptor partial agonist whereas clozapine is an M1 antagonist in vitro and in vivo. We hypothesized that NDMC may improve cognition by increasing dopamine (DA) and acetylcholine (ACh) release in medial prefrontal cortex (mPFC) via direct stimulation of M1 receptors, whereas both NDMC and clozapine itself would do so by other mechanisms as well, and that clozapine would inhibit the M1 agonist effect of NDMC. In the present study, using microdialysis in awake, freely moving rats, we found that NDMC at doses of 10 and 20, but not 5 mg/kg, significantly increased DA and ACh release in the mPFC and HIP, but not in the nucleus accumbens (NAC). The M1-preferring antagonist, telenzepine (3 mg/kg), completely blocked NDMC (10 mg/kg)-induced increases in cortical DA and ACh release. Clozapine (1.25 mg/kg), which by itself had no effect on DA or ACh release in the cortex, blocked NDMC (10 mg/kg)-induced ACh, but not DA, release in the mPFC. The 5-HT1A receptor antagonist, WAY100635 (0.2 mg/kg) blocked NDMC (20 mg/kg)-induced cortical DA but not ACh release. These findings suggest that: (1) NDMC is an M1 agonist while clozapine is an M1 antagonist in vivo; (2) M1 agonism of NDMC can contribute to the release of cortical ACh and DA release; (3) NDMC, because of its M1 agonism, may more effectively treat the cognitive impairments observed in schizophrenia than clozapine itself; and (4) M1 receptor agonism may be a valuable target for the development of drugs that can improve cognitive deficit in schizophrenia, and perhaps other neuropsychiatric disorders as well.
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PMID:N-desmethylclozapine, a major metabolite of clozapine, increases cortical acetylcholine and dopamine release in vivo via stimulation of M1 muscarinic receptors. 1590 Mar 18

Cognitive deficits are a fundamental feature of the schizophrenic disorder, but the effect of antipsychotic treatment is still debated. The study assesses the effect of olanzapine on neurocognitive functioning and symptomatology of patients with schizophrenic disorder residual type. Executive function evaluation by the Wisconsin card sorting test (WCST) was performed on 39 patients treated with olanzapine (5-20 mg/day); the efficacy of drug in improving symptomatology, safety and quality of life was also evaluated. After 7 months of treatment, the mean number of WCST categories tended to increase. Correct responses increased with a statistically significant change from the baseline. The total and unique errors decreased significantly. At all post-baseline visits a decrease from baseline in the PANSS total, positive and negative scores was seen. The proportion of patients with less severe illness (CGI), increased over the course of the study with a corresponding decrease of patients with more severe illness. The quality of life scores also tended to improve during treatment. The Simpson Angus scale, Barnes-akathisia and abnormal involuntary movement scale scores decreased consistently. The most common treatment emergent drug related adverse events were weight gain, insomnia, agitation and anxiety. Neurocognitive functioning in terms of executive performance and symptomatology improved in people with schizophrenia residual type.
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PMID:Executive function assessment of patients with schizophrenic disorder residual type in olanzapine treatment: an open study. 1599 Dec 59

Cognitive deficits are a central and debilitating aspect of schizophrenia and other major mental illnesses. Although they are largely refractory to pharmacotherapy, multiple studies have now shown that large and lasting improvements in cognition can result from behavioral interventions. We will review our work over the past 10 years demonstrating that cognitive remediation treatment together with work therapy or supported employment can lead to large, lasting, and clinically relevant improvements in cognition and work functioning. While we will make some references to the work of others in these same areas, this is not a general review of these areas of research. Instead, the goal is to provide the rationale for the progression of our studies, describe the methods, and summarize the results, so that readers may understand, critique, and improve upon what we have done.
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PMID:Cognitive remediation and vocational rehabilitation for schizophrenia. 1607 90

Cognitive deficits may index genetic liability for schizophrenia and are candidate endophenotypes for the illness. In order to compare the degree of sensitivity among cognitive tasks to group differences between healthy relatives and controls and the influence of moderator variables, this review reports mean effect sizes for 43 cognitive test scores from 58 studies of cognitive performance in the unaffected adult relatives of schizophrenia patients. Results indicate reliable relative-control differences, in the small to medium effect size range, over a diverse array of tasks, with the largest effect sizes seen in complex versions of continuous performance tasks, auditory verbal learning, design copy tests, and category fluency. Three study design features were found to have significant effects on overall effect size magnitude: groups unmatched on education, groups unmatched on age, and asymmetric psychiatric exclusion criteria. After excluding studies with the latter 2 design features, reliable performance differences were still observed over a smaller subset of cognitive test variables, with the largest effect sizes seen in Trails B (d = 0.50) and performance measures from both simple (d = 0.56) and complex (d = 0.60-0.66) versions of continuous performance tasks. Four of the 6 largest effect sizes reflect tasks with high executive control demands in common, such as working memory demands, set shifting, and inhibition of prepotent responses. Cognitive deficits, particularly those tapping such executive control functions, should continue to prove valuable as endophenotypes of interest in the search for specific genetic factors related to schizophrenia.
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PMID:Cognitive deficits in unaffected first-degree relatives of schizophrenia patients: a meta-analytic review of putative endophenotypes. 1616 12

In the first part the meaning of terms cognition and cognitive dysfunction is clarified. Cognitive dysfunction is found in many neuropsychiatric disorders. Majority of studies were done in patients with schizophrenia and dementia. For studying cognitive dysfunction, the most appropriate appear the initial phases of the disease. The next part of the study summarizes the treatment possibilities of cognitive dysfunction in schizophrenia. Atypical antipsychotics represent the basal treatment. The improvement of cognitive deficit by atypical antipsychotics is significant, but its importance in real life is small. The new add-on treatment has the potential for further improvement of cognitive dysfunction. This approach includes augmenting effects of neurotransmitters related to cognition (glutamate, noradrenalin, serotonin, acetylcholine). The improvement of cognitive dysfunction can improve the long-term outcome and functional prognosis in patients suffering from schizophrenic disorder.
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PMID:[Cognitive dysfunction and its therapy]. 1638 50

Medically, insight is a multidimensional concept. Results of previous studies are inconclusive regarding the relationship between insight and global and cognitive functions. The aim of this study was to evaluate the relationship among insight, patients' global function, cognitive function of patients with schizophrenia and their key caregivers' perception about this disorder. Thirty-one patients with schizophrenia were recruited. Cognitive function such as memory index proved to be a significant predictor for patients' insight; environmental factors such as caregivers' perception was not. In addition to cognitive deficit, whether the other factors such as genetic variability, medication use, environmental factors, and illness severity, etc., could influence insight of patients will still be a controversial issue. Further multidimensional survey of the relationship with insight in a larger and comprehensive design is necessary.
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PMID:The relationship among insight, cognitive function of patients with schizophrenia and their relatives' perception. 1640 Dec 40

Cognitive deficits predict functioning in schizophrenia; however, little is known as to whether the association is present in other mental disorders. If specific cognitive deficits uniquely predict functional impairment in schizophrenia the association of select aspects of brain dysfunction with daily living would suggest an intervention target and perhaps a means by which to improve the functioning of schizophrenia patients. The relationship of cognition and functioning was investigated in schizophrenia (n=39), bipolar affective disorder (n=27), and nonpsychiatric control (n=38) participants to determine whether the associations varied across groups. We examined verbal memory, verbal learning, verbal fluency, vigilance, executive functioning, symptomatology, and generalized cognitive functioning for associations with social function. Correlational analyses revealed particular cognitive domains (e.g., verbal memory) to be associated with social functioning in schizophrenia, bipolar, and control subjects; however generalized cognitive function and symptomatology were also associated with social functioning in patients. Multiple regression analyses revealed that in schizophrenia poor verbal memory predicted worse social functioning even after the effects of generalized cognitive dysfunction were considered. Verbal memory indices failed to account for variance in social function in bipolar patients and control subjects after consideration of generalized cognitive function. Bipolar patients with worse planning and problem solving tended to have worse social functioning. Therefore, unlike schizophrenia patients who may fail to process verbally mediated material, bipolar patients' difficulty with logical approaches to problems in daily living may have the greatest impact on their community function.
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PMID:Does cognition predict community function only in schizophrenia?: a study of schizophrenia patients, bipolar affective disorder patients, and community control subjects. 1644 48

Dopaminergic afferents arising from the ventral tegmental area (VTA) are crucial elements in the neural circuits that mediate arousal, motivation, and reinforcement. Two major targets of these afferents are the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAc). Whereas dopamine (DA) in the mPFC has been implicated in working memory and attentional processes, DA in the NAc is required for responding to reward predictive cues. These distinct functions suggest a role for independent firing patterns of dopaminergic neurons projecting to these brain regions. In fact, DA release in mPFC and NAc can be differentially modulated. However, to date, electrophysiological studies have largely overlooked heterogeneity among VTA neurons. Here, we provide direct evidence for differential neurotransmitter control of DA neural activity and corresponding DA release based on projection target. Kappa opioid receptor agonists inhibit VTA DA neurons that project to the mPFC but not those that project to the NAc. Moreover, DA levels in the mPFC, but not the NAc, are reduced after local infusion of kappa opioid receptor agonists into the VTA. These findings demonstrate that DA release in specific brain regions can be independently regulated by opioid targeting of a subpopulation of VTA DA neurons. Selective control of VTA DA neurons projecting to the mPFC has important implications for understanding addiction, attention disorders, and schizophrenia, all of which are associated with DA dysfunction in the mPFC.
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PMID:Kappa opioids selectively control dopaminergic neurons projecting to the prefrontal cortex. 1647 3

Deficits in perceptual organization have been consistently reported in schizophrenia, as has an association between these deficits, disorganized symptoms, and poorer premorbid functioning and prognosis, suggesting that they may be an index of illness severity or progression. It is unclear, however, whether the impairment is present at, or before the first psychotic episode. This study examined perceptual organization in young people considered to be at high-risk for schizophrenia, defined by the "close-in" strategy [Yung, A.R., McGorry, P.D., McFarlane, C.A., Jackson, H.J., Patton, G.C., Rakkar, 1996. Monitoring and care of young people at incipient risk of psychosis. Schizophrenia Bulletin, 22, 283-303]. The high-risk group (n=70) was compared to first-episode patients (n=54), and nonpatients (n=24) using a task with known sensitivity to perceptual organization deficits in schizophrenia, and whose scores have predicted long-term outcome and disorganized symptomatology in past studies [Knight, R.A., Silverstein, S.M., 1998. The role of cognitive psychology in guiding research on cognitive deficits in schizophrenia. In Lenzenweger, M., Dworkin, R.H., (Eds.), Origins and Development of Schizophrenia: Advances in Experimental Psychopathology. APA Press, Washington DC, pp. 247-295.; Silverstein, S.M., Knight, R.A., Schwarzkopf, S.B., West, L.L., Osborn, L.M. Kamin, D., 1996b. Stimulus configuration and context effects in perceptual organization in schizophrenia. Journal of Abnormal Psychology 105, 410-420.; Silverstein, S.M., Schenkel, L.S., Valone, C., Nuernberger, S., 1998a. Cognitive deficits and psychiatric rehabilitation outcomes in schizophrenia. Psychiatric Quarterly 69, 169-191.; Silverstein, S.M., Bakshi, S., Chapman, R.M., Nowlis, G., 1998b. Perceptual organization of configural and nonconfigural visual patterns in schizophrenia: effects of repeated exposure. Cognitive Neuropsychiatry 3, 209-223]. There were no differences between groups, and the first-episode group demonstrated non-significantly more sensitivity to stimulus organization than the other groups. When the high-risk group was broken down into its 3 subgroups (A--family history of psychotic illness and recent drop of 30+ points in the GAF scale; B--history of attenuated psychotic symptoms; C--brief limited intermittent psychotic symptoms), only group A demonstrated evidence of impairment, but this group differed significantly only from first- and young, later-episode schizophrenia patients, not from nonpatients. These findings are consistent with recent data on pre-attentive processes in schizophrenia which indicate that performance is not impaired and may even be enhanced, early in the illness, with dysfunctions beginning with increased chronicity.
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PMID:Perceptual organization in first episode schizophrenia and ultra-high-risk states. 1649 84


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