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)

In summary, neuronal nicotinic systems are important for a variety of aspects of cognitive function impacted by antipsychotic drugs. It has been demonstrated that antipsychotic drugs have memory and attentional impairing effects when given to unimpaired subjects. Nicotine can reduce some of these impairments, but antipsychotic drug administration can also attenuate nicotine effects. We have found that nicotinic agonists selective for alpha7 and alpha4beta2 receptor subtypes significantly improve learning and memory. Serotonergic actions of antipsychotic drugs may decrease efficacy of nicotinic co-treatments. When the antipsychotic drug clozapine and nicotine are administered to subjects with cognitive impairments caused by NMDA glutamate receptor blockade or hippocampal dysfunction they can significantly attenuate the attentional and memory impairments. Nicotine has been shown in our studies to reverse the memory impairment caused by acute clozapine-induced memory improvement. Acute risperidone and haloperidol has been shown to attenuate nicotine-induced memory improvement. We have determined the role of hippocampal alpha7 and alpha4beta2 nicotinic receptors in the neural basis of nicotinic antipsychotic interactions. Local acute and chronic hippocampal infusion of either nicotinic alpha7 or alpha4beta2 antagonists cause significant spatial working memory impairment. Chronic hippocampal nicotinic antagonist infusions have served as a model of persistent decreases in nicotinic receptor level seen in schizophrenia and Alzheimer's disease. Clozapine attenuated the memory deficit caused by chronic suppression of hippocampal alpha4beta2 receptors while the amnestic effects of clozapine were potentiated by chronic suppression of hippocampal alpha7 receptors. Nicotinic co-treatment may be a useful adjunct in the treatment of schizophrenia, to attenuate cognitive impairment of schizophrenia. Nicotine as well as selective nicotinic alpha7 and alpha4beta2 receptor agonists significantly improve working memory and attentional function. Nicotine treatment was found to be effective in attenuating the attentional and memory impairments caused by the psychototmimetic NMDA antagonist dizocilpine (MK-801), a model of the cognitive impairment of schizophrenia. Studies of the interactions of antipsychotic drugs with nicotinic agents provided quite useful information concerning possible co-treatment of people with schizophrenia with nicotinic therapy. Nicotine was found to significantly attenuate the memory impairments caused by the antipsychotic drugs clozapine and olanzapine. Interestingly, nicotine-induced cognitive improvement was significantly attenuated by the antipsychotic drug clozapine. One of the principal effects of clozapine is to block 5HT2 receptors. Ketanserin a 5HT2 antagonist significantly attenuated nicotine-induced improvements in attention and memory. Thus it appears that antipsychotic drugs with actions blocking 5HT2 receptors may limit the efficacy of nicotinic co-treatments for cognitive enhancement.
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PMID:Nicotinic-antipsychotic drug interactions and cognitive function. 1701 89

The effect of ZSET1446 (spiro[imidazo[1,2-a]pyridine-3,2-indan]-2(3H)-one) on cognitive impairment in mice, previously treated with methamphetamine (METH) at a dose of 1 mg/kg for 7 days, was investigated. ZSET1446 showed a significant ameliorating effect on METH-induced impairment of recognition memory, although it had no effect on exploratory behavior. ZSET1446 (1 microg/kg) recovered the defect of the novelty-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in the prefrontal cortex (PFC) of METH-treated mice. The compound increased phosphorylated ERK1/2 levels in the hippocampus but not PFC of naive mice without affecting the total ERK1/2 levels. The ameliorating effect of ZSET1446 on recognition memory in METH-treated mice was negated by pretreatment with a mitogen-activated protein kinase/extracellular signal-regulated kinase kinase inhibitor, SL327 (alpha-[amino-(4-aminophenylthio)methylene]-2-(trifluoromethyl)phenylacetonitrile). Furthermore, the dopamine D1 receptor antagonist, SCH23390 [R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine], and N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 [5H-dibenzo[a,d]cyclohepten-5,10-imine (dizocilpine maleate)], blocked the ameliorating effect of ZSET1446 on METH-induced memory impairment, whereas the D2 receptor antagonist, raclopride, had no effect. These results suggest that the ameliorative effect of ZSET1446 on METH-induced memory impairment is associated with indirect activation of ERK1/2 following stimulation with dopamine D1 and NMDA receptors of the PFC. ZSET1446 would be a potential candidate for further preclinical study aimed at the treatment of cognitive deficits in Alzheimer's disease and schizophrenia, as well as METH psychosis.
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PMID:A novel azaindolizinone derivative ZSET1446 (spiro[imidazo[1,2-a]pyridine-3,2-indan]-2(3H)-one) improves methamphetamine-induced impairment of recognition memory in mice by activating extracellular signal-regulated kinase 1/2. 1709 Jul 2

Contextual effects were explored in schizophrenia patients and paired comparison subjects during a long-term face recognition task. The objective was to investigate the contextual effects on face recognition by manipulating, in the same experiment, the perceptual context of the face (intrinsic vs. extrinsic) and the task context (inclusion vs. exclusion instructions). The situation was derived from the Jacoby's [Jacoby, L.L., 1991. A process dissociation framework: separating automatic from intentional uses of memory. Journal of Memory and Language 30, 513-541] process dissociation procedure. The results showed that schizophrenia patients (N=20) presented lower performances than healthy controls (N=20) in the inclusion but not in the exclusion task. This observation emphasizes the heterogeneity of recollection and suggests that the memory impairment in schizophrenia reflects an imbalance between two mechanisms. The first is a deficit in "associative recollection", i.e., the failure to use efficiently associative information. The other is an enhanced "discriminative recollection" that impedes their capacity to process information separately from its perceptual context. In addition, correlation with symptoms suggest that the former is expressed in the loosening of associations characteristic of disorganization symptoms, whereas the latter reflects the lack of flexibility or the contextualization bias related to psychotic symptoms, i.e., delusions and hallucinations.
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PMID:Use of the process dissociation procedure to study the contextual effects on face recognition in schizophrenia: familiarity, associative recollection and discriminative recollection. 1712 45

To examine retrieval-induced forgetting (RIF) in schizophrenia, subjects studied category-exemplar words taken from either strong or weak categories, and then practiced retrieval by completing category word-stems on half of the word pairs. Patients had reduced recall and recognition, but showed the expected RIF effect of better recall of unpracticed items from unpracticed categories than for unpracticed items from practiced categories. By contrast, patients and controls showed differing RIF for recognition as a function of categorical dominance: whereas controls showed RIF only for dominant category exemplar word pairs, patients showed RIF for both dominant and weak categories. Different patterns of baseline practiced retrieval for weak associate pairs in schizophrenia may explain this finding. The results failed to support faulty RIF in the associative memory impairment of schizophrenia.
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PMID:The role of retrieval inhibition in the associative memory impairment of schizophrenia. 1718 66

Cognitive impairments in schizophrenia have been recognized as a prominent feature of the illness. Research is now focusing on determining a relationship between neurocognitive impairments, and social and functional outcome. Despite a number of comprehensive reviews on neurocognitive measures and reports on spatial working memory abnormalities in patients with schizophrenia when compared to healthy volunteers, there have been no meta-analyses of the extent of the abnormality in this group of patients. We reviewed 33 studies (from 1992 to 2005) on spatial working memory impairment in schizophrenia with the aim of providing a quantitative assessment of the consistency and the magnitude of the deficit. From the quantitative data analysis, it is evident that patients with schizophrenia are consistently more impaired on the spatial working memory measures than healthy controls. These impairments may be related to social disability and explain some cognitive deficits that characterize the clinical presentation of schizophrenia.
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PMID:Behavioural studies of spatial working memory dysfunction in schizophrenia: a quantitative literature review. 1729 70

The central goals of this manuscript are (1) to better characterize what appears to be the most parsimonious account of schizophrenic long-term memory impairment in the neuropsychological literature: a contextual binding deficit rooted in the medial temporal lobes; (2) to link this deficit to concrete abnormalities at the level of the hippocampus; and (3) to suggest that this deficit could lead to the functional impairment experienced by schizophrenia patients in their daily lives. As far as long-term memory is concerned in schizophrenia, there seems to be a general agreement to conclude that explicit mechanisms are disturbed compared to relatively spared implicit mechanisms. More precisely, both subsystems of explicit memory (i.e., episodic and semantic) appear to be dysfunctional in this patient population. Errors during the encoding processes could be responsible for this dysfunction even if retrieval per se is not totally spared. Recently, a number of studies have suggested that impairments in conscious recollection and contextual binding are closely linked to episodic memory deficit. Since the hippocampal formation is considered to be the central element in the neural support for contextual binding and episodic memory, we have conducted an extensive review of the literature concerning the hippocampal formation in schizophrenia. Emerging evidence from varying disciplines confirm the coherence of the different anomalies reported concurrently at the neuroanatomical, neurodevelopmental, biochemical, and genetic levels. It seems highly probable that the synaptic disorganization in the hippocampus concerns the regions crucial for encoding and contextual binding memory processes. The consequences of these deficits could result in schizophrenia patients experiencing major difficulties when facing usual events which have not been encoded with their proper context.
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PMID:Hippocampal abnormalities and memory deficits: new evidence of a strong pathophysiological link in schizophrenia. 1730 84

Cognitive and psychiatric determinants of impairment of complex activities of daily living (ADLs) were investigated in 33 schizophrenic patients and 16 normal comparison subjects. The schizophrenic patients were cognitively impaired and were deficient in the ADL. However, the impairment of ADL could not be explained specifically by impairment of higher-order executive function or by negative symptoms: memory functions were more related to impairment of ADL and positive symptoms as much as the negative ones. Positive symptoms were significantly related to commissive errors in the ADL, whereas negative symptoms were nonsignificantly related to omissive errors. Negative symptoms were significantly more related to memory impairment than to impairment on measures of higher-order executive function (working memory). This investigation demonstrates that an ecologically oriented approach to test development and measurement of ADL is fruitful in understanding schizophrenia-especially if it is constrained by cognitive constructs compatible with the phenomenology of the disease.
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PMID:Neuropsychological and activity of daily living script performance in patients with positive or negative schizophrenia. 1744 26

Memory impairment is a core feature in schizophrenia (SZ). The aim of this study was to investigate short-term memory (STM) and its sensitivity to distraction with visual-spatial material. This study comprised 23 recent-onset SZ patients and 23 healthy controls. The degree of disruption upon recall from interleaving irrelevant items within a sequence of to-be-remembered items-the sandwich effect [Hitch, G. J. (1975). The role of attention in visual and auditory suffix effects. Memory and Cognition, 3, 501-505]-was examined. STM performance, whether in the presence or absence of distraction, was poorer and markedly more vulnerable to disruption in SZ. Our results suggest that processing spatial information in STM is susceptible to interference in SZ.
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PMID:Processing spatial-temporal information in recent-onset schizophrenia: the study of short-term memory and its susceptibility to distraction. 1746 6

Lurasidone (SM-13496) is a novel atypical antipsychotic with high affinities to dopamine D2, serotonin 5-HT7, 5-HT2A, 5-HT1A receptors and alpha2C adrenoceptor. In this study, the effects of lurasidone on the rat passive-avoidance response and its impairment by the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (dizocilpine) were evaluated and compared with those of other antipsychotics. The passive-avoidance response was examined by measuring the step-through latency, 1 day after the animals received foot-shock training. When given before the training session, lurasidone did not affect the passive-avoidance response at any dose tested (1-30 mg/kg, p.o.). All the other atypical antipsychotics examined (i.e., risperidone, olanzapine, quetiapine, clozapine and aripiprazole), however, significantly reduced the step-through latency at relatively high doses. A pre-training administration of lurasidone significantly and dose-dependently reversed the MK-801-induced impairment of the passive-avoidance response. At doses lower than those that affected the passive-avoidance response, risperidone, quetiapine, and clozapine partially reduced the MK-801-induced impairment, whereas haloperidol, olanzapine, and aripiprazole were inactive. In addition, the post-training administration of lurasidone was as effective in countering the MK-801 effect as the pre-training administration, suggesting that lurasidone worked, at least in part, by restoring the memory consolidation process disrupted by MK-801. These results suggest that lurasidone is superior to other antipsychotics in improving the MK-801-induced memory impairment and may be clinically useful for treating cognitive impairments in schizophrenia.
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PMID:Lurasidone (SM-13496), a novel atypical antipsychotic drug, reverses MK-801-induced impairment of learning and memory in the rat passive-avoidance test. 1766 68

Recent neuroimaging and postmortem studies have reported abnormalities in white matter of schizophrenic brains, suggesting the involvement of oligodendrocytes in the etiopathology of schizophrenia. This view is being supported by gene microarray studies showing the downregulation of genes related to oligodendrocyte function and myelination in schizophrenic brain compared to control subjects. However, there is currently little information available on the response of oligodendrocytes to antipsychotic drugs (APDs), which could be invaluable for corroborating the oligodendrocyte hypothesis. In this study we found: (1) quetiapine (QUE, an atypical APD) treatment in conjunction with addition of growth factors increased the proliferation of neural progenitors isolated from the cerebral cortex of embryonic rats; (2) QUE directed the differentiation of neural progenitors to oligodendrocyte lineage through extracellular signal-related kinases; (3) addition of QUE increased the synthesis of myelin basic protein and facilitated myelination in rat embryonic cortical aggregate cultures; (4) chronic administration of QUE to C57BL/6 mice prevented cortical demyelination and concomitant spatial working memory impairment induced by cuprizone, a neurotoxin. These findings suggest a new neural mechanism of antipsychotic action of QUE, and help to establish a role for oligodendrocytes in the etiopathology and treatment of schizophrenia.
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PMID:Quetiapine facilitates oligodendrocyte development and prevents mice from myelin breakdown and behavioral changes. 1768 94


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