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

In chronic schizophrenics, disordered motor development in childhood is followed by more early cognitive and social impairment and poorer outcome; childhood schizophrenics represent the most extreme variants of this. Preschizophrenic infants show a fluctuating dysregulation of maturation--or "pandevelopmental retardation" (PDR)--that involves physical growth; gross motor, visual-motor, and cognitive development; proprioceptive and vestibular responses; muscle tone; and possibly arousal. Pandevelopmental retardation was significantly related to a genetic history for schizophrenia (less than .05), but not to obstetric complications. The severity of PDR was significantly related to the severity of later psychiatric and cognitive disorder (less than .01). Pandevelopmental retardation provides a "marker" in infancy for the inherited neurointegrative defect in schizophrenia. These disordered functions should be studied by anyone interested in the biology of the schizophrenic genotype or in specific early interventions for children at risk.
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PMID:Neurobiologic antecedents of schizophrenia in children. Evidence for an inherited, congenital neurointegrative defect. 26 19

Over the last few years, psychological experiments have provided a major contribution to research in schizophrenia. Historical, practical and theoretical grounds led to investigations mainly in the field of cognitive disorder. Independent psychological theories of schizophrenia emerged from the body of experimental results, at first restricted to mental performance of the patients but later generalized to center on the total problem of schizophrenia. In accordance with psychiatric thinking, psychologists favoured cognitive deficit as the essential schizophrenic characteristic which would possibly generate the basic symptomatology. Apart from methodological considerations, the main question arising is if this feature is truly typical of schizophrenia. The problem of the different concepts of schizophrenia has to be considered in this connection. A survey of theories of schizophrenia which are sufficiently consolidated by psychological experiments reveals that two lines of theoretical reasoning exist: one based on specific cognitive disorder, and the other where this is not the case. Encompassed by the first classification are the considerations of Bannister, Rodnick and Germezy, Shakow, McReynolds, Silvermann, L.J. Chapman, Payne, Mednick, and Epstein, as well as the interference theories (with the exception of Callaway's version)..
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PMID:[Theories of cognitive disorder in schizophrenia based on psychological experiments (author's transl)]. 109 May 48

Cognitive disorders are neither a unique nor a constant phenomenon in schizophrenia. Among the dysfunctions that may be observed at times, primarily during acute phases and in patients with a non-paranoid symptomatology, certain disturbances in attention-focusing and information processing seem to be most conspicuous. Some of these cognitive dysfunctions may have been transmitted from parent(s) to the patient, either genetically or through simple forms of learning. the empirical evidence for this assumption is to be found in the fact that some of the same cognitive deficits as those found in schizophrenic patients also found in their first-degree relatives, although usually in a milder form. Other forms of cognitive dysfunction may have developed as complementary strategies in response to communication deviances and cognitive behavior found in their parents. A developmental model, in which genetic, physiological and environmental factors are included is described as a way of illustrating how predisposing factors, as well as intermediating and stress factors, contribute to the debut and maintenance of cognitive disorders in schizophrenics.
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PMID:Cognitive disturbances in schizophrenics: what are they, and what is their origin? 328 78

Experimental research into language in schizophrenia has been guided traditionally by two main assumptions: that language disturbance is widespread among schizophrenic patients and easy to detect and measure, and that schizophrenia is fundamentally a cognitive disorder in which language disturbance is part of an inability or failure to regulate one's thoughts. However, recent findings have challenged both assumptions. Two experiments are reported here, the first based on monologues, the second on conversations, which were subjected to reconstruction and discourse analyses. Schizophrenic material is found to be harder to follow than normal, and is characterised by poor reference networks and inappropriate use of questions. While some of the results are specific to the schizophrenic group, others are found also in affective patients, but none is the product of formal thought disorder. The central problem lies less in cognition than in the social process of taking the role of the other.
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PMID:Language in schizophrenia. The structure of monologues and conversations. 401 43

This study reports on a new rating scale, the short version (GIP-28) of the Dutch Behavioral Rating Scale for Geriatric Inpatients (GIP). Only a limited number of items was needed to adequately describe GIP variance in two patient samples (n = 2196 and n = 126). Based on previous results factor analysis produced three factors: 'apathy', 'cognitive' and 'affective' symptoms. This led to the construction of new subscales which showed significant differences between persons in different patient settings. Elderly patients with a cognitive disorder or schizophrenia/mood disorder according to DSM-IV criteria, were correctly classified in almost 80% of the cases. We conclude that the GIP-28 is equivalent to the GIP and describes aspects of apathy and cognitive and affective symptoms in elderly patients. A compact rating scale like this might best be used in (routine) screening of cognitive and noncognitive behavioral problems. It may also prove useful for outpatient purposes.
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PMID:[Short version of the Dutch Behavioral Rating Scale for Psychogeriatric Inpatients (GIP-28)]. 938 20

The aim of the present study is to test Brenner's model of cognitive functioning in schizophrenia. It is assumed that elementary cognitive disorders (attention and encoding) and complex cognitive disorders (recall, concept formation) reinforce each other. Cognitive disorders are supposed to cause detrimental effects on functional outcome. We used cognitive rehabilitation as a strategy to induce cognitive changes in 27 patients assigned to treatment groups following the cognitive modules of the Integrated Psychological Treatment (IPT). Ten schizophrenic patients without cognitive impairments worked as a control group. With only one minor conceptual change (replacing concept formation with executive function, a more comprehensive construct), we found that our data fitted with Brenner's model. A relationship has been found between neuropsychological improvements and higher levels of autonomy and social functioning. These findings have important implications not only for cognitive assessment but also for selecting targets in cognitive rehabilitation.
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PMID:Cognitive mechanisms, psychosocial functioning, and neurocognitive rehabilitation in schizophrenia. 1295 1

Developmental defects in neuronal positioning and synaptic connectivity are commonly found in neurological diseases, and they are believed to underlie many cognitive and affective disorders. Several mouse mutants are currently available that model at least some aspects of human developmental brain disorders. With the identification of the genes mutated in these animals and the study of the cellular basis of the phenotypes, we have taken significant strides toward an understanding of the mechanisms controlling proper brain development and the consequences of their dysfunction. In particular, mouse mutants deficient in the Reelin gene have provided valuable insights into the mechanisms of cortical development. Absence of Reelin expression in the spontaneous mutant mouse reeler leads to extensive defects in neuronal position and dendrite development. In humans, loss of Reelin results in a type of lissencephaly with severe cortical and cerebellar malformation. Genetic and biochemical studies using mouse mutants suggest that the Lis1 protein may participate in the Reelin signaling pathway controlling cortical development. Reduced levels of Reelin are also present in postmortem brains of patients with schizophrenia, suggesting a possible link with this cognitive disorder. The regulation of the Reelin gene may thus provide insights into the mechanisms of this disease.
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PMID:Reelin mouse mutants as models of cortical development disorders. 1626 28

In the last two decades, understanding of the dynamics of dopamine function in the prefrontal cortex and its role in prefrontal cortex physiology has opened up new avenues for therapeutic interventions in conditions in which prefrontal cortex function is compromised. Neuropsychological and imaging studies of prefrontal information processing have confirmed specific cognitive and neurophysiological abnormalities in individuals with schizophrenia. Because such findings are also observed in the healthy siblings of patients with schizophrenia, they may represent intermediate phenotypes related to schizophrenia susceptibility genes.Catechol-O-methyltransferase (COMT) represents an important candidate as a susceptibility gene for cognitive dysfunction in schizophrenia because of the unique role this enzyme plays in regulating prefrontal dopaminergic function. A functional COMT polymorphism (Val158Met) predicts performance in tasks of prefrontal executive function and the neurophysiological response measured with electroencephalography and functional magnetic resonance imaging in tasks assessing working memory. In fact, individuals with the Val/Val genotype, which encodes for the high-activity enzyme resulting in lower dopamine concentrations in the prefrontal cortex, perform less well and are less efficient physiologically than Met/Met individuals. These findings raise the possibility of new pharmacological interventions for the treatment of prefrontal cortex dysfunction and of predicting outcome based on COMT genotype. One strategy consists of the use of CNS-penetrant COMT inhibitors such as tolcapone. A second strategy is to increase extracellular dopamine concentrations in the frontal cortex by blocking the noradrenaline (norepinephrine) reuptake system, a secondary mechanism responsible for the disposal of dopamine from synaptic clefts in the prefrontal cortex. A third possibility involves the use of modafinil, a drug with an unclear mechanism of action but with positive effects on working memory in rodents. The potential of these drugs to improve executive cognitive function by selectively increasing dopamine load in the frontal cortex but not in subcortical territories, and the possibility that response to them may be modified by a COMT polymorphism, provides a novel genotype-based targeted pharmacological approach without abuse potential for the treatment of cognitive disorder in schizophrenia and in other conditions involving prefrontal cortex dysfunction.
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PMID:Treatment of cognitive deficits associated with schizophrenia: potential role of catechol-O-methyltransferase inhibitors. 1757 98

Allon Therapeutics Inc is developing AL-108, an intranasally administered, eight-amino-acid peptide fragment (known as NAP) of activity-dependent neuroprotective protein, and AL-208, an intravenous formulation of NAP. AL-108 is undergoing phase II trials for cognitive impairment in Alzheimer's disease and schizophrenia. AL-108 is also being investigated as a neuroprotective agent, including for the treatment of Parkinson's disease and ocular disease. AL-208 is undergoing phase II clinical trials for the treatment of cognitive disorder and phase I clinical trials for ocular disease and cognitive deficits associated with coronary artery bypass graft or ischemia.
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PMID:AL-108 and AL-208, formulations of the neuroprotective NAP fragment of activity-dependent neuroprotective protein, for cognitive disorders. 1860 May 85

The histamine H3 receptor is a pre-synaptic auto- and hetero-receptor that controls the release of histamine and a variety of other neurotransmitters in the brain. As such, modulation of the histamine H(3) receptor is expected to affect wake via control of the release of histamine and to affect cognition via regulation of several other neurotransmitters including acetylcholine and norepinephrine. Over the last several years numerous pre-clinical studies have shown that histamine H3 antagonists promote wakefulness, improve cognition, and in some cases affect food intake. Based on the interest level generated from these early pharmacology studies, and following the cloning and expression of the human histamine H3 receptor, many pharmaceutical companies began drug discovery programs aimed at the identification of histamine H3 antagonists suitable for human clinical trials. These efforts have led to many new chemotypes, and several promising compounds have recently entered the clinic for a variety of conditions, including ADHD, Narcolepsy, EDS associated with Narcolepsy, Cognitive disorders and Schizophrenia. Recent efforts towards the identification and pharmacological characterization of novel histamine H3 antagonists will be discussed.
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PMID:Histamine H3 antagonists as wake-promoting and pro-cognitive agents. 1867 68


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